SEMINAR ON TUMORS OF THE THYHUS

CASE i DIAGNOSIS S.P. I

1 Ttl,Ymoma, class ical, benign R75-1514 2 Thymoma, lymphocytic predominance UH75-2533 3 Mal ignant t hymoma, metastatic R76-91 4 t~a l ignant t hymoma in a chi ld R76-1369 5 t~a 1 ignant thymoma , sarcomatoid R76-1363 6 Hodgkin's disease of thymus UH74- 4:2.1.7. 7 Halignant lymphoma, lymphoblastic, of thymus R76-1219 8 lola 1 i gnant lymphoma vs. thymoma R76-355 9 Yolk sac tumor of mediastinum R76-231

10 Carcinoid tumor of thymus R76-1291

'

SEMINAR ON PATHOLOGY OF THE THYMUS

Or. Juan Rosai Professor of Pathology and Director of Anatomic Pathology

University of Minnesota Medical School Minneapolis, Minnesota

CASE 1 - (R75-1514; Courtesy of Dr . Thomas R. Hal l in , MethodistHospital, l~inneapoli s). 66-year-old male with history of myasthenia gravis for 6 years, whi ch appeared fo 11 o~1i ng an appendectomy. The main symptoms were di pl opi a, bilateral ptosis and difficulty in chewi ng. A recent chest x-ray s ho1~ed a 6cm. mass located in the anterior mediastinum. Laboratory tests were normal. A thoracotomy was performed and an encapsulated tumor was found. The posterior aspect of this tumor was adherent to the pericardium. There were also fibrous adhesions with left lung and chest w~ll.

CASE :2- (#UH75-2533): 25-year-old female 1~ith a history of chronic cough and corticaria. Chest x-rays showed a mass in the anterior mediastinum, which was removed in its entirety. Grossly, it was an encapsulated tumor measuring 9x8x5 .. Scm. The cross section was so 1 i d, homogeneous, of a grayish white color. The slides are from this tumor. 8 months later, the patient consulted because of recurrence of the urticaria. A retroperitonea 1 lymph­angiogram sho~ted enlarged lymph nodes interpreted as suspicious of lymphoma.

£ASE 3- (#R76-91; Courtesy of Dr . Richard J. Reed, Tulane University, New Orleans, Louisiana). 53-year-old male with history of mediastinal tumor excised in 1968. The tumor recurred locally some years later and metastases occurred, which led to the death of the patient. At autopsy, there was massive recurrence in the mediastinal region as ~tell as metastases in liver and bones. The Seminar slides are from the liver metastases.

CASE 4 - ( #R76-1369 ; Courtesy of Dr. John ~1. Temp 1 eton, St. Joseph' s Hospital, Memphis, Tennessee). 11 -year-old girl with dyspnea and retrosternal oppression of short duration. Chest x-ra.Ys sh01~ed a large mass in the ant erior mediastinum, ~thich was biopsied.

CASE 5- (#R76-1363; Courtesy of Dr. Wayne Chadbourn, Metropolitan Medical Center, Minneapolis). 67-year-old female with a tumor in anterior superior mediastinum. At operation, a soHd mass measuring 15cm in greatest diameter 1~as found invading the lung.

CASE 6 - (#UH74-4212): 13-year-old girl 1~ith retrosternal oppression. Chest x-rays showed a large multinodular mass in anterior superior mediastinum. There was no cervical lymphadenopathY. A thoracotomy was performed and a multi­nodular tumor ~tas found in the thymic region. A partial resection was carried out followed . by a course of radiation therapy.

CASE 7- (#R76-1219; Courtesy of Dr. Nikola Kostich, Northwestern Hospital, 11inneapoli s). 24-year-old male, asymptomatic, with mass in anterior superior mediastinum found in a routine chest x-ray. At operation, an apparently encap­sulated tumor ~tas found and this was easily removed.

CASE 8- {#R76-355 ; Dourtesy of Dr. F.J. Martinez Tello, Ciudad Sanitaria 13 de Octubre, Madrid, Spain}. 24-year-old female in whom a routine chest x-ray showed a mass i n the anterior mediastinum. There ~1as no previous symptomatology. The gross specimen showed a lOcm. tumor 1~hich was well circumscribed, except for an area of infi ltration into the lung. There was no evidence of mediastinal lymphadenopathy.

CASE 9 - {GR76-231; Courtesy of Dr. Robert W. Weber, USAF Medical Center, Keesler Air Force Base, Mississippi}. 19-year-old male wi th large tumor mass in anterior superior mediastinum without evidence of distant metastases . The tumor was excised. The ~~eight was 400gms . and the dimensions 12x8x6cm. It ~1as en­capsulated and showed a solid cross section of grayish color and multiple areas of necrosis , hemorrhage and cystic degeneration. The consistency was soft.

CASE 10- {IR76-1291; Courtesy of Or. Thomas Swallen , North Memorial Hospital, Minneapolis). 35-year-old male. In 0Gtober 1975 a bronchial tumor was excised and diagnosed as carcinoid tumor. A year later a mediastinal mass measuring 6x3x3cm 1~as found in t he anterior superior mediastinum. Labor a tory tests showed persi stent elevation of serum calcium parathyroid hormone associated with decrease of phosphor us. The med iastinal mass was excised and t he neck was exposed. 3 large parathyroid glands were found and 2 of them were excised. The Seminar slides are from the mediastinal tumor.

SEMINARIO SOBRE PATOLOGIA DEL TIMO Dr . Juan Rosa i

Profesor de Patolog1a y Director de Anatom1a Patologica, Escuela de Medicina de la Universidad de Minnesota, 11inneapolis, Hinnesota, Estados Unidos .

CASO 1 - (#R75-1514; Cortesfa del Dr. Thomas R. Hallin , Methodist Hospital, Minneapolis) . Hombre de 66 anos con historia de miastenia gravis por 6 anos, aparecida luego de una apendectomfa. Los si ntomas principales eran diplopia, ptosis bilateral y dificultad a la masticacion. Una radiografia de t6rax reciente mostr6 una masa de 6 em localizada en mediastina anterior . Las pruebas de labora­torio eran norma les . Se efectu6 toracotomia, encontrandose un tumor encapsul ado cuya parte posterior estaba adherida al pericardia. Habia tambi en adherencias flbrosas entre pulm6n izquierdo y pared costal. ~. ·~~

CASO 2- (#UH75-2533): Mujer de 25 anos con historia de tos cr6nica y urticar1a. Radiograffa de t6rax revelo una masa en medi astina anterosuperior, que fue extirpada en su totalidad. El aspecto macrosc6pico era el de un tumor encap­sulado de 9x8x5.5 em. La superficie de corte era s6lida , homogenea, de color blanco grisaceo. Las laminillas del Seminario corresponden a este tumor. A los 8 meses de la operacion, la enferma consul to por recidiva de la urticaria. Lin­fangiografia retroperitoneal demostro ganglios agrandados, interpretados como sospechosos de linfoma.

CASO 3 - (#R76-91; Cortes1a del Dr. Richard J. Reed, Tulane University, Ne~1 Orleans, Louisiana) . Hombre de 53 anos con historia de tumor mediastinal extirpado en 1968. El tumor recidiv6 localmente unos anos despues y aparecieron metastasis a distancia que llevaron al fallecimiento del enfermo. En la autopsia, se encontr6 recidiva masiva en region mediastinal y metastasis en h{gado y huesos. Las la­mini ll as del Seminario corresponden a las metastasis hepaticas.

CASO 4- (#R76-1369; Cortes1a del Or. John W. Templeton, St. Joseph's Hospital, Memph1s , Tennessee}. Nina de 11 anos con sintomas de disnea y opresi 6n retroes­ternal de corta duraci6n. La radiografia de t6rax demostro una gran masa en

mediasti na anterior, de la que se tom6 una generosa biopsia.

CASO 5 - (R76-1363; Cortesi a de 1 Or. Wayne Chadbourn , Metropolitan Medica 1 Center, Minneapolis} . Mujer de 67 anos con tumor en mediastina anterosuperior . Ala operaci6n , se encont r6 una masa salida de 15 em de diametro maximo, con areas de invasion pulmonar .

CASO 6 - (#UH74-4212): Nina de 13 anos que acude a la consulta por sensaci6n de opresion retroesternal. La radiograffa de t6rax muestra una gran masa multi­lobulada ocupando mediastina anterosuperior. No hay evidencia de adenopat1a cervical. Se efectu6 toracotom1a, encontrandose un tumor multinodul ar en la region tfmica. Una reseccion parcial fue llevada a cabo , seguida por un curso de radio­terapia.

GASO 7 - (R76-1219; Cortesia del Dr. Nikola Kostich, North~1estern Hospital Minneapolis). Hombre de 24 anos, asintomatico, con masa en mediastina antero­superior encontrada en radiografi'a de rutina. A la operaci6n, se encontr6 un tumor aparentemente encapsulado, que fue facilmente extirpado.

CASO 8 - (#R76-355; Cortesia del Dr. F.J . Martinez Tello, Ciudad Sanitaria l ~ de Octubre, Madrid, Espana). Mujer de 24 anos ala que se descubri6 en radio­graffa de t6rax de rutina una masa en mediastina anterior. No habia sintomato­logia previa. La pieza macrosc6pica correspondfa a una tumoraci6n de 10 em de diametro, que era bien delimitada salvo en una zona en que infi l traba el pulm6n. No habia evidencia de adenopat ias mediastinicas.

CASO 9- (#R76-231; Cortesia del Or. Robert W. Weber, USAF Medical Center, Keesler Air Force Base, 11ississippi). Hombre de 19 anos con gran masa tumoral en mediastina anterosuperior, sin evidencia de metastasis a distancia. El tumor fue extirpado. Pesaba 400 gm y media 12xSx6 em. Estaba encapsulado y tenia una super­ficie de corte solida, de color grisaceo y multiples areas de necrosis, hemorragia y degeneracion qu1stica . La consistencia era blanda.

CASO 10- (R76-1291; Cortesia del Dr. Thomas Swallen, North Memorial Hospital, 11inneapolis). Hombre de 35 aiios. En octubre de 1975, un tumor bronquial fue extirpado y diagnosticado como tumor carcinoide. Un aiio mas tarde presenta una masa mediastinal de 6x3x3 em en mediastina anterosuperior. Examenes de laboratorio demostraron elevaci6n persistente de calcio serico y hormona paratiroidea, asociadas con disminuci6n del fosforo. La masa mediastinal fue extirpada y elcuello fue exp1orado. Se encontraron tres glandulas paratiroideas agrandadas; dos de ellas f~eron extirpadas. Las laminillas del Seminario corresponden al tumor mediastinal.

• ~I l"t t ~·, •

SENINARIO SOBRE PATOLOGIA DEL TI:10 Or. Juan Rosai

Profesor de Patologfa y Director de Anatom1a Patologi ca, Escuel a de 1·1edicina de la Uni versidad de f·1innesota, f1inneapoli s , l'linnesota, Estados Unidos.

Venezuela, mayo de 1977

CASO 1 - (i1R75-1514; Cortes1a del Dr. Thomas R. Hal lin, f1ethodist Hospital, ~Hnneapol is). Hombre de 66 anos con historia de miastenia gravi s por 6 aiios, aparecida l uego de una apendectomia. Los sintomas principales eran diplopia, ptosis bilat eral y dificultad a la masticaci6n. Una radiograna de t6rax reciente mostro una masa de 6 em localizada en mediastina anterior. Las pruebas de labora­tori o eran normales. Se efectuo toracotomi'a , encontrandose un tumor encapsul ado cuya parte posterior estaba adherida al pericardia. Habi'a ta~bien adherencias fibrosas entre pulm6n izquierdo y p~red costal. ·

CASO 2 - (#UH75-2533): Hujer de 25 alios con his tori a de tos cr6nica y urticar1a . Radiografia de t 6rax revelo una masa en mediastina anterosuperior, que fue exti rpada en su tota 1 i dad. El aspecto macroscopi co era e 1 de un tumor encap-

· sulado de 9x8x5.5 em. La superficie de corte era s61ida , homogenea , de color blanco grisaceo. Las laminillas del Seminario corresponden a este tumor . A los 8 meses de la operaci6n, la enferma consult6 por recidiva de la urticaria . Lin­fangiografia re troperitoneal demostro gangli os agrandados, interpretados como sospechosos de 1 infoma .

CASO 3- (#R76-91; C~rtesia del Dr. Richard J. Reed, Tulane Univers i ty, New Orleans, Louisiana). Ho~re de 53 anos con historia de tu~~r mediastinal extirpado en 1968. El tumor recidiv6 local mente unos aiios despues y aparecieron metastasis a distancia que llevaron al fallecimiento del enfenr~ . En la autopsia , se encontro recidiva masiva en regfor. H~diastinal y metastasis en h{gado y huesos . Las la­minil las del Seminarto corresponden a las metastasis hepaticas.

CASa 4 - (#R76-1369; Cor tesfa del Dr . John \L Templ eton, St. Joseph ' s Hospital, Memphis, Tennessee). Nina de 11 aiios con sintomas de disnea y opresion retroes­ternal de corta duracian. La radiografia de torax demostro una gran rnasa en

mediastina anteri or, d~ 1a que se tom6 una generosa biopsia.

CASO 5- (R76-l353 ; Cortesia del Or. Wayne Chadbourn, l·letropolitan f·ledica1 Center, Minneapolis). Nujer de 67 anos con tumor en medi astina anterosuperior. Ala operacion, se encontro una masa solida de 15 em de diametro maximo , con areas de invasion pulmonar.

CASO 6 ~ (#UH74-4212): Nina de 13 anos que acude a la consulta por sensacion de opresion retroesternal. La radiografia de torax muestra una gran masa mul ti­lobulada ocupando mediastina anterosuperior. No hay evidencia de adenopatia cervical; Se efectuo toracotomia, encontrandose un tumor multinodular en la region timica. Una reseccion parcial fue llevada a cabo, seguida por un curso de radio­terapia.

CASO 7 - {R76-1219; Cortesia del Or. Nikola Kostich, tlorth11estern Hospital ~linneapolis). Hombre de 24 aiios, asintomatico, con masa en rr.ediastino antero­superior encontrada en radiografia de rutina. Ala operacion, se encontro un tumor aparentemente encapsulado, que fue facilmente extirpado.

CASO 8- (#R76-355; Cortesia del Or . F.J. Martinez Tello, Ciudad Sanitaria 1~ de Octubre, Madrid, Espana). Mujer de 24 aiios a la que se descubrio en radio­grafia de torax de rutina una masa en mediastina anterior . No habfa sintomato­logia previa. La pieza macrosc6pica correspondia a una tuu.~raci6n de 10 em de diametro, que era bien delimitada salvo en una zona en que infiltraba el pulmon. No habia evidencia de adenopatias mediastinicas .

CASO 9 - {#R76-231; Cortesia del Or. Robert ~1. Weber, USAF Medical Center, Keesler Air. Force Base, Mississippi). Hombre de 19 anos con gran masa tumoral en rrediastino anterosuperior, sin evidencia de metastasis a distancia. El tumor fue extirpado.Pesaba 400 gm y media 12x8x6 em. Estaba encapsulado y tenia una super­ficie de corte salida, de color grisaceo y multiples areas de necrosis,hemorragia y degeneracion qui s ti ca. La cons 1 s tenci a er.a b 1 and a.

CASO 10- (R76-1291; Cortesia del Or. Thomas S~1a ll en, North 1-!emorial Hospital, Minneapolis). Hombre de 35 aiios. En octubre de 1975, un tumor bronquial fue extirpado y diagnosticado como tumor carcinoide. Un aiio mas tarde presenta una ~sa mediastina l de 6x3x3 em en mediastina anterosuperior. Examenes de laboratorio demostraron elevaci6n persi stente de calcic serico y hormona paratiroidea, asociadas con disminucion del fosforo . La masa mediastinal fue extirpada y elcuell o fue explorado. Se encontraron t res glandulas paratiroideas agrandadas; dos de ellas fueron extirpadas. Las laminillas del Seminario corresponden al tumor mediastinal.

CASO 1 - Tlt~OMA, BENIGNO

Bernatz, P.E., Harrison, E.G., and Clagett, O.T.: Thymoma: A clinicopathologic study. J. Thorac. Cardiovasc . Surg., 42:424-444, 1961.

castleman, B.: Tumors of the thymus gland. Fascicle 19, Atlas of Tumor Pathology, Washington, Armed Forces Institute of Pathology, 1955 .

Lattes, R. : Thymoma and other tumors of the thymus; an analysis of 107 cases . Cancer, 15:1224-1260, 1962.

Legg, M.A., and Brady, W.J.: Pathol ogy and cl inical behavior of thymomas; a survey of 51 cases. Cancer, 18:11 31-1144, 1965.

lev\ne, u.tl., Rosai, .l. , 'Bearman, R., and ?o11iacl<., 1>..: \he fine structure of thymoma, with emphasis on i ts different1a1 diagnosis; a s tudy of 10 cases. 1\m. J. Pathol., 81:4g-86, 1975.

Mittage, T., Kornfeld, P., Tormay, A., and Woo, C.: Detect ion of anti-acetylcholine receptor factors in serum and thymus from patients with myasthenia gravis. N. , ~ Engl. J. Med., 294:691 -694, 1976. . ,

O'Gara, R.W., Horn, R.C. , Jr., and Enterline, H.T.: Tumors of the anterior mediastinum. Cancer, 11:562-590, 1958.

Oldham, H.N . , Jr., and Sabiston, D.C., Jr.: Primary tumors and cysts of the mediastinum. Monogr . Surg . Sci., 4:243-279, 1967.

Rosai , J . , et al. : Tumor s of the thymus. Atlas of tumor Pathol ogy, Fascicle 19, 2nd Series, Washington, D.C., Armed Forces Institute of Pat hology, 1976.

Salyer , N. R., and Eggleston, J.C . : Thymoma; a clinical and pathological study of 65 cases. Cancer , 37:229-249, 1976.

Ste~1art, H.L., and Snell, K.C.: Thymomas and thymic hyperplasia in Praomys (Mastomys) natalensis. Concomitant myositis, myocardi tis, and sialodacryoadeno­itis. J. Natl. cancer Inst . , 40:1135-1159, 1968.

Stutman, 0., Yunis, E.J., and Good, R.A.: Carcinogen-induced tumors of the thymus I. Restoration of neonatally thymectomized mice with a functional thymoma. J. Hatl. Cancer Inst., 41:1431 - 1452, 1968; II. Lung colonies as a means of sepa­rating different cell types of a functional thymoma. J. Natl. Cancer Inst., 42:783-795, 1969; III . Restoration of neonatally thymectomized mice with thymomas in cell - impermeable chambers. J. Nat . Cancer Inst. , 43:499-508, 1969.

Thomson, A.D. , and Thackr ay, A.C.: The histology of tumours of t he thymus. Br . J . Cancer, 11 :348-357 , 1957 .

Wa tanabe, H. : A pathological study of t hymomas . Acta Pathol . Jap .• 16:323-358, 1966.

CASO 2 - TIMOMA A PREDOMINIO LINFOC ITARIO.

Knight, S., Bradley, J. , Oppenheim, J.J., and Ling, N.R.: The in vitro trans­formation of thymocytes and lymphocytes from humans, rabbits and guinea-pigs and from thymomas. Clio. Exp . Immunol., 3:323-341, 1968.

Levine, G.D., and Polliack, A.: The T-cell nature of the lymphocytes in two human epithelial thymomas: A comparative immunologic, scanning and transmission electron microscopic study. Clin. Immuno . Immunopathol., 4:199-208, 1975.

' ' CASO 3 - t-1ETASTASIS HEPATICA DE TIMOHA ~IALIGNO.

Bernatz, P.E., Khonsari, S., Harrison, E.G., Jr., and Taylor, W.F.: Thymoma : factors influencing prognosis. Surg. Clin. North Am. 53:885-892 , 1973.

Ericsson, J., and Hook, 0.: Malignant thymoma with metastases. A report of three cases, two with myast henia gravis. J. Neuropathol. Exp . Neurol., 19:538-553, 1960.

Fechner, R. E. : Recurrence of noninvasive thymomas. Report of four cases and review of literature . Cancer, 23: 1423-1 427, 1969.

Guillan, R.A., Zelman, S., Smalley, R. L., and Iglesias, P.A.: Malignant thymomas as­sociated with mJasthenia gravis, and evidence of extra-thoracic metastases. An analysis of published cases and report of a case. Cancer, 27 :823-830, 1971.

Hirst, E., and Robertson, T.I.: The syndrome of thymoma and erythroblastopenic anemia . A review of 56 cases including 3 case reports. Medicine, 46:225-264, 1967 .

Mottet, N.K.: ~1alignant thymoma. Am._J . Clin. Pathol. , 41 :61-71,1964. Papatestas, A. E., Alpert, L.I., Osserman, K.E., Osserman , R.S., and Kark, A.E.: Studies in myas thenia gravis: effects of thymectomy. Results on 185 patients with nonthymomatous and thymomatous mJasthenia gravis, 1941-1969. Am. J. Med., 50: 465-474, 1971.

Rosen, V.J., Christiansen, T.~l., and Hughes, R.K.: Metastatic thymoma presenting as a solitary pulmonary nodule. Cancer, 19:527-532, 1966.

CASO 4- TI MOMA MALIGNO (INFANTIL} . Chatter\, J., and Katz, S.l~.: Thymoma in a 17-year-old boy . Cancer, 37:953-957, 1976. Dehner, l.P., Martin, S.A., and Sumner, H.W.: Thymus related tumors and tumor-like lesions in childhood with rapid clinical progression and death. Human Pathol., (en prensa, Enero 1977) .

Halpern, S.R., Schoelzel, E. , and Johnson, R.B.: Thymoma in a young child producing symptoms of asthma. Am. J . Dis. Child . , 111:99-104, 1966 .

Talerman, A., and Amigo, A.: Thymoma associated with aregenerative and aplastic anemia in a five -year-old child. Cancer, 21:1212-1218, 1968.

CASO 5 - TI MOMA ~IALIGNO, SARCOMA TO IDE. Chapek, M .14. , Rosa i , J. , and levine, G. D. : Ma 1 i gnant thymoma with rhabdomyosarco­matous ("myoid cell "} differentiation; report of a case and review of the literature. Am. J. Surg. Pathol. (en prensa).

Friedman, N.B.: -Tumors of the thymus. J. Thorac. Cardiovasc . Surg., 53:163-182, 1967 . Henry K.: An unusual thymic tumour with a striated muscle (myoid) component (with a brief review of the literature on myoid cells). Br. J. Di s . Chest, 66:291-299, 1972 .

Levine, G. D., a·nd Bensch, K.G.: Epithelial nature of spi ndle-cell thymoma. An ultra­structural study . Cancer, 30:500-511, 1972.

Seemayer, T.A., Jerry, L.M., Shapiro, L., and Su ll ivan, A.K.: Spindle-cell epitheli al thymoma; Fine-structural and tumor lymphocyte observations. Am. J. Clin. Pathol., 65:612-622. 1976 .

Van de Velde, R.l. , and Friedman, N.B.: ThYmic mYOid cells and myasthenia gravis . Am. J. Pathol ., 59:347-367, 1970.

Wekerle, H., Paterson, B., Ketelsen, U. -P., and Feldman, M.: Striated muscle fibers differentiate in monolayer cultures of adult thymus reticulum. Nature, 256:493 , 1975.

-.

GASO 6 - ENFERHEDAD DE HODGKIN DEL TH10.

Ewing, J.: The thymus and its tumors, report of t hree cases of thymoma. Surg. Gynecol. Obstet ., 22:461-472, 1916.

Fechner, R.E.: Hodgkin's disease of the thymus. Cancer, 23:16-23, 1969.

~atz, A., and Lattes, R.: Granulomatous thymoma or Hodgkin's disease of the thymus? A clinical and histologic ·study and a re-evaluation. Cancer, 23:1-15, 1969.

Keller, A.R., and Castleman, B.: Hodgkin's disease of the thymus gland. Cancer, 33:1615-Hi23, l974.

Lo~tenhaupt, E., and Brown, R.: Carcinoma of the thymus of granulomatous type; a clinfcal and pathological study. Cancer, 4:ll93-1209, 1951.

~~rshall, A.H.E., and Wood, C.: The involvement of the thymus in Hodgkin's disease. J. Pathol., 73 :163-166, 1957.

Nickels, J ., Franssila, K., and Hjelt, L.: Thymoma and Hodgkin's disease of the thymus. Acta Pathol. ~licrobiol. Scand. (A) 81 :l-5, 1973.

Remigio, P.A.: Granulomatous thymoma associ.ated ~lith erythroid hypoplasia. Am. J. Clin. Pathol. , 55:68-72, 1971.

, CASO 7 - LINFOMA LINFOBLASTICO DE TIMO.

Adams, J.E .: Leukemogenic thymoma. Report of a unique case. Am. J. Clin. Pathol., 40:173-182, 1963.

Cooke, J.V.: Mediastinal tumor in acute leukemia; clinical and roentgenologic study. Am. J. Dis. Child., 44:1153-ll?l, 1932.

Kersey, J.H., Sabad, A., ·Gajl-Peczalska, K., Hallgren, H.M., Yunis , E.J ., and Nesbit, H. E.: Acute lymphoblastic leukemic cells with T (thymus-derived)lymphocyte markers . Science, 182:1355-1356, 197 3. ·

Nathwani, B.N., Kim, H., and Rappaport, H.: Malignant lymphoma, lymphoblastic .. Cancer, · 38: 964'-983, 1976.

Sen, L., and Borella, L.: Clinical importance of lymphoblasts 1~ith T markers in childhood acute leukemia. N. Engl. J. Med., 292:828-832, 1975.

Smith, J.L., Barker, C.R., Clein, G.P., and Collins, R.D.: Characterisation of malignant mediastinal lymphoid neoplasm (Sternberg sarcoma} as thymic in origin. Lancet, 1:74-77, 1973.

CASO 8 - LINFbHA MALIGNO DE TIMO VERSUS TIM0t1A MALIGNO.

Oanisch, F., and Nedelmann , E.: Bosartiges Thymom bei einem 3~ jahrigen kind mit eigenartiger metastasierung ins zentratnervensystem. Vircho1~s Arch. (Pathol. Anat.) 268:492-514, 1928.

, CASO 9 - TERATOI1A MALIGNO DE MEDIASTINO, (REGION TIMICA), TIPO SACO VITELINO (SEND ENDOD~RMICO).

Levine, G.D.: Primary thymic seminoma-a neoplasm ultrastructurally similar to testicular seminoma and distinct from epithelial thymoma. Cancer, 31:729-741, 1973.

Martini, N., Golbey, R.B., Hajdu, S. I., ~lhitmore, l~.F., and Beattie, E.J., Jr.: Primary mediastinal germ cell tumors. Cancer, 33:763-769, 1974.

Oberman, H.A., and Libcke, J .H. : Hal ignant germinal neoplasms of the mediastinum. Cancer, 17:498- 507, 1964.

Pachter, M.R., and Lattes, R.: "Germinal" tumors of t he mediastinum: A clinico­pathologic study of adult teratomas, teratocarcinomas, choriocarcinomas and seminomas. Dis. Chest, 45:301 - 310, 1964.

Pedersen, H.: Tumors of t he anterior mediastinum; a report of an endodermal sinus tumour and of six metastasizing tumours of possible thymic origin . Ac ta Pathol . Scand. , Supp 1. , 112:128-141 , 1970.

Schantz, A., Se1~all, W., and Castleman, B. : Nediastinal germi noma. A study of 21 cases with an ,exce 11 ent prognosis . Cancer, 30:1189-1194, 1972.

CASO 10 - TUt~OR CARCINOIDE DE TIHO

Cohen, R.B., Toll, G.O., and Castleman, B. : Bronchial adenomas in Cushing ' s syndrome: their relation to thymomas and oat.cell carcinomas associated with hyperadreno­corticism. Cancer, 13:812-817, 1960.

Hosoda, S., Suzuki, H. , Kito , H., Hiai, H., Akamine, Y. , Murakami, H., Kosukegawa, K. , Kato, N., Yura, J., and Miyachi, Y.: Argyrophilic thYmic carci noid-clinico­pathologic study of four cases . Acta Path . Jap., 25:717-740, 1975 .

Levine, G.O . , and Rosai , J.: A spindle cel l variant of thymi c carcinoid tumor; a clinica l , histol ogic, and fine structural study with emphasis on its distincti on from spindle cel l thymoma. Arch. Pathol ., 100:293-300, 1976 .

Lowent~a l , R.M. , Gumpel , J.l1. , Kreel , L., MCLaughlin, J. E., and Skeggs, D.B .L.: Carcinoid tumour of the thymus vli t h syst emic manifes tations: a radiological and pathologi cal study. Thorax, 29 :553- 558, 1974.

~lanes, J.L., and Taylor, H.B . : Thymic carcinoid in famil ial multiple endocrine adenomatosis . . Arch . Pathol., 95:252-255, 1973 .

Rosai, J., and Higa, E.: Mediastinal endocrine neoplasm, of probable thymic origin, related to carcinoid tumor . Clinicopathologic st udy of 8 cases. Cancer, 29: 1061-1074 , 1972.

Rosai, J . , Higa, E., and Davie, J . : t•lediastinal endocr ine neoplasm in patients with multipl e endocrine adenomatosis; a previously unrecogni zed association. Cancer, 2'9:1075-1083 , 1972.

Rosai , J., Levine, G., Weber, W.R., and Higa, E. : Carcinoid tumors and oat cell carci noma of ' the t hymus. Pathol. Ann . 11:201-226, 1976,.

Salyer, \~ . R . , Salyer , D.C. , and Eggleston, J.C. : Carcinoid tumors of t he thymus. cancer, 37:958-973, 1976 .

CASE 1 - THYi10NA (BENIGN)

Bernatz, P.E., Harrison, E.G., and Clagett, O.T.: Thymoma: A clinicopathologic study. J. Thorac. Cardiovasc . Surg., 42 :424-444, 1961.

Castl eman, B.: Tumors of the thymus gl and . Fascicle 19, Atlas of Tumor Pathology, Hashington , Armed Forces Institute of Pathology, 1955.

Lattes, R. : Thymoma and other tumors of the thymus; an analysis of 107 cases. Cancer, 15 :1224-1260, 1962 .

Legg, 1·1.A., and Brady, W. J.: Patho 1 ogy and cl in i ca 1 behavior of thymomas; a survey of 51 cases. Cancer, 18:1131-11 44, 1965.

Levine, G.D., Rosai, J., Bearman, R., and Poll iack, A.: The fine structure of thymoma, with emphasis on i ts differential diagnosis; a study of 10 cases. Am. J. Pathol., 81:49-86, 1975.

Hittage, T. , Kornfeld, P., Tormay, A., and \~oo, c.": Detection of anti -acetylcholine receptor factors in serum and thy1111.1s from patients with myasthenia gravis. N. Engl . J. Med .', 294:691-694 , 1976.

O'Gara, R.W., Horn, R.C., Jr., and Enterline, H.T.: Tumors of the anterior mediastinum. Cancer, 11:562-590, 1958.

Oidharn, H.N., Jr., and Sabiston, D.C., Jr.: Primary tumors and cysts of the mcdi asti num. 1·1onogr. Surg. Sci., 4:243-279, 1967.

Rosai, J., et al.: Tumors of the thymus. Atlas of tumor Pathology, Fascicle 19, 2nd Series, Washington, D.C., Armed Forces Institute of Pathology, 1976.

Salyer, ' W.R. , and Eggleston , J.C.: Thymoma; a clinical and pathological study of 6~ cases. cancer , 37:229-249, 1976.

Stewart, H.L., and Snell, K.C.: Thymomas and thymic hyperplasia (Nastcmys) natalensis. Concomitant myositis, myocarditis , and itis. J. Ratl. cancer Inst. , 40: 1135-1159, 1968.

in Praomys sialodacryoadeno­.,_

Stutman, 0., Yunis, E.J., and Good, R.A.: Carcinogen-indu~ed tumors of the thymus I. Restoration of neonatally thymectomi zed mice with a func t i ana 1 thymoma. J. Natl. Cancer Inst., 41 :1431·· 1452, 1968; I I. Lung colonies as a means of sepa ­rating different cell types of a functional thymoma. J. Natl. Cancer Inst., !;2:783-795, 1969; I II. Res toration of neonatally thymectomized mice with thymomas in cell-impermeable chambers. J. Nat. Cance~ Inst., 43:499-508, 1969.

Thomson , A.n •• and Thackray , A.C.: The histology of tumours of the thymus . Br. J. Cancer , 11 :348-357, 1957.

Watanabe, H. :. A pat hological study of thymomas. Acta Pathol. Jap., 16:323-358, 1966 '

CASE 2. THYMOMA (BENIGN), PRED0:1INAimY LYMPHOCYTIC

;:night, S., Bradley, J., Oppenheim, J.J., and Ling, N.P. . : The in vitro trans­formation of thymocytes and lymphocytes from humans, rabbits and guinea-pigs and from thymomas. C1in . Exp. Inrnunol . , 3:323-341 , 1968.

Levine, G. D. , and Polliack, A. : The T-cel l nature of the lymphocytes i n t1~o human epithel i al thymomas: A comparative immunologic, scann·ing and transmission electron microscopic study. Clin. Immune. Immuncpathol., 4:199- 208, 1975 .

CASE 3 - ~Ll\LIGNAilT THY HOt !A (HEPATIC t1ETASTAS IS)

Serna tz, P. E. , Khonsari, S. , Harrison, E.G. , Jr. , and Taylor, W. F. : Thymoma: factors influencing prognosis. Surg. Clin. North Am. 53:885-892 , 1973.

Ericsson, J., and Hook, 0.: f·lalignant thymoma with metastases . A report of three cases, two •.vith myastheni a gravis. J. lleuropatho1. Exp. Neural., 19:538-553, 1960.

Fechner, R.E.: Recurrence of noninvasive thymomas. Report of four cases and review of literature. Cancer, 23:1423-1427, 1969.

Guillan, R.A., Zelman, S., Smalley , R.L., and Iglesias, P.A.: ~1a1ignant thymomas as­sociated with myasthenia gravis, and evidence of extra-thoracic metastases. An analysis of published cases and repor t of a case. Cancer, ?.7:823-830, 1971.

Hirst, E., and Robertson, T.I.: The syndrome of thymoma and erythroblastopenic anemia. A revie~1 of 56 cases including 3 case reports. Nedicine, 46:225-264, 1967.

Nottet, N.K.: t•lalignant thymoma. Am. J. Clin. Pathol ., tlJ:61-71, 1964.

Papatestas, A. E., Alpert, L.I., Ossermcfn, K.E., Osserman, R.S., and Kark, A.E.: Studies in mYasthenia gravis: effects of thymectomy. Results on 185 patients with nonthymomatous and thymomatous myasthenia gravis, 1941 -1969. Am. J. ~~d., 50: 465-474, 1971.

~sen, V.J., Christiansen , T.W., and Hughes, R.K.: Metastatic thymoma presenting a.s a solitary pulmonary nodule. Cancer, 19:527-532, 1966.

I CASE 4 - 11ALIGNANT THYf.10NA ( Ii'lFANTILE) 1

Chatten, J., .and Katz, S.M.: Thymoma in a 17-year-old boy. Cancer, 37:953-957, 1976.

Dehner, L.P., Martin, S.A. , and Sumner, H.W.: Thymus related tumors and tumor- l ike lesi ons in childhood with rapid clinical progression and death. Human Pathol., (in press, Jan 7!) j -

Halpern, S.R .• Schoelzel, E., and Johnson, R.B.: Thymoma in a young- child prcducing symptoms of asthma. ~m. J. Ois. Child., 111:99-104, 1966.

Talerman, A. , and Amigo, A.: Thymoma associated with aregenerative and aplastic anemia in a five-year-old child. Cancer, 21:1212-1218, 1968.

I

CASE 5 - 11ALIGtiAtiT THYMDr1A (SARCOMATOID) ;

Chapek, M.~l., Rosai, J ., and· Levi ne , G. D.: Malignant thymoma with rhabdomycsarco­matous ("myoid cell") differentiation; report of a case and review of the literature. A.11. J. Surg. Pathol.(in press) ·

Friedman , N.B.: Tumors of the· thymus. J. Thorac. Cardiovasc. Surg., 53:163-182, 1967 .

Henry K.: An unusual thymic tumour with a striated muscle (myoid) component (with ·a brief review of the literature on myoid cells) . Br. J. Dis. Chest, 66:291-299, .1972 .

levine, G.D., and Bensch, K.G.: Epith~lial nature of spindle-cell thymoma. An ultra­structural study. Cancer, 30:500-511, 1972.

Seemayer, T.A., Jerry, l .M., Shapiro, L., and Sullivan, A.K.: Spind~e-cell epithelial ~1ymoma; Fine-structural and tumor lymphocyte observaticns. Am. J. Clin. Pathol., 65:612-622, 1976. .

Van de Veldc, R.L., and Friedman, N.B.: Thymic myoid cells and myasthenia gravis. Am. J. Pathol., 59:347-367, 1970.

Wekerle, H., Paterson, B., Ketelsen, U.-P., and Feldman, H.: St:-iated muscle fibers differentiate in monolayer cultures of adult thymus reticul um. Nature, 256:t193, 1975.

CAS E 6 - HODGKIN'S DISEASE OF THE THYtiUS

£1·ling, J.: The thymus and its tumors, report of three cases of thymoma. Surg. Gynecol. Obstet., 22:461-472, 1916.

Fechner, R.E.: Hodgkin's disease of the thymus . Cancer, 23:16-23, 1969.

Katz , A., and Lattes, R.: Granulomatous thymoma or Hodgkin's disease of the thymus? A clinical and histologic study and a re-evaluation. Cancer, 23:1-15, 1969.

Keller , A.R., and Castleman, B.: Hodgkin's disease of the thymus gland. Cancer, 33:1615-1623, 1974.

L01·1enhaupt, £., and Brown, R.: Carcinoma of the thymus of granulomatous type; a clinical and pathological study. Cancer, 4:1193- 1209, 1951.

~~rshall, A.H.E., and Wood, C.: The involvement of the thymus in Hodgkin 's disease. J. Pathol., 73:163-166, 1957.

Nickels, J., Franssila, K., and Hjelt, L.: Thyw~ma and Hodgkin's disease of the thymus. Acta Pathol. ~!icrobiol. Scand. (A) 81:1-5, 1973.

Remigio, P.A.: Granulomatous th.Ymoina associated l'lith erythroid hypoplasia. Am. I!J .. . J •

J. Cl in. Pathol ., 55:68-72, 1971.

CASE 7 - ~IALJGNAtH LYf1PHOMA OF THYMUS, LYt1PHOBLASTIC TYPE

I Adams, J.E.: Leukerogenic thymoma. Report of a unique case. Am. J. Clin. Pathol.,

. 40:173-182, 1963.

Cooke, J.V .: Mediastinal tumor in acute leukemia; clinical and roentgenologic study. Af!l· J. Dis. Child., 44:1153-1177, 1932.

Kersey-; J.H., Sabad, A., Gajl :.Peczalska, K., Hallgren, H.f1., Yunis, E.J., and Nesbit, M.E.: Acute lymphoblastic leukemic cells ~lith T {thymus-derived)lymphocyte markers . Science, 182:1355-1356,1973.

Nathwani, B.N., Kim, H., and Rappaport, H.: Malignant lymphoma, lymphoblastic:: Cancer, 38:964-983, 1976.

Sen, L., and Borella , L.: Clinical importance of lymphoblasts with T markers in childhood acute leukemia. N. Engl. J . Med., 292:828-832, 1975.

Smith, J.L., Barker, C.R., Clein, G.P., and Collins, R.O.: Characterisation of malignant mediastinal lympho·id neoplasm {Sternberg sarcoma) as thymic in origin. Lancet, 1 :74-77, 1973.

t~E a - MALIGNANT LYMPHOMA OF nmrus vs. MALIGNANT nmlOtiA 1 I

Oanisch,- F. , and Nedelmann , E.: Bosartiges Thymom bei einem 3ls, jahrigen kind mit e1 genarti ger metastasierung ins zentratnervensystem. V·i rchows Arch. { Pa tho 1. Anat.) 268:492-514, 1928. ·

CASE 9 - MALIGNANT TERATOMA OF MEOIASTINU~! THY!UC REGIOfi) , TYPE YOLK SAC TUI10R .{QIDODERHAL S NUS TOf10R

Levine, G.O.: Primary thymic semi noma-a neoplasm ultrastructurally similar to testicular seminoma and distinct from epithelial thymoma. Cancer, 31:729-741, 1973.

~lartini, N., Golbey, R.B., Hajdu, S.I., Whitmore, W.F., and Beattie, E.J., Jr.: Primary mediastinal germ cell tumors. Cancer, 33:763-769, 197'L

Oberman, H.A., and Libcke , J.H.: ~1alignant germinal neoplasms of the mediast inum. Cancer, 17: 4g8- 507, 1964.

Pachter, I·LR., and Lattes , R.: "Germinal" tumors of the mediastinum: A clini co­pathologic study of adult teratomas , teratoca~cinomas , choriocarci nomas and seminomas . Di s. Chest, 45 :301 -310 , 1964.

Pedersen, H.: Tumors of the anted or mediastinum; a report of an endoderrnal sinus tumour and of six metastasizing tumours of possi ble thymic origi n. Acta Pa thol . Scand. , Suppl. , 112:1 28-141, 1970.

Schantz, A., Se1~all, w., and Castleman, B.: Nediastinal germinoma . A study of 21 cases with ar excellent prognosi s . Cancer, 30:1189-1194, 1972.

CASE lD - CARCINOID TUI10R OF THYt.IUS

Cohen, R.B., Toll, G.D ., and Castleman, 13.: Bronchi al adenomas in Cushing's syndrome': t hei r rel ation to t hymomas and oat ce 11 carci nomas associ a ted 11i th hyperadl·eno­corticism. Cancer, 13:81 2-817 , 1960.

~ ~!J Hosoda, S., Suzuki, H., Kito, H., Hiai, H., Akamine, Y., Murakami, 11., Kosukegawa, ' ,. K., Kato, N., Yura, J., and Miyachi, Y.: Argyrophilic thymic carcinoid-clinico- ' pathologic st~dy of four cas~s. Acta Path. Jap., 25:717-740 , )g75.

Levine, G.D., and Rosai, J.: A spindle cell variant of thymic carcinoid tumor ; a clinical, histologic, and fine structural study with emphasis on its distinction from spindl e cell thymoma. Arch. Pathol., 100:293-300, 1976 .

Lowenthal, R.M., Gumpel, J.M. , K~eel, L. , Mclaughl in , J. E., and Skeggs, D.B. L.: Carcinoid tumour of the thYmus with systemic manifestations: a radiological and pathological study. Thorax, .29:553-558, 1974. . . .

Manes, J.L., and Taylor, H.B .: Thymic carci noid i n familial mul tiple endocrine adenomatosis. Arch . Pathol ., 95:252-255, 1973.

Rosai, J ., and Higa, E.: Mediastinal endocrine neoplasm, of probable thymic origin, related to carcinoid tumor. Clinicopathologic study of 8 cases. Cancer, 29: 1061-1074, 1972.

Rosai, J., Higa, E., and Oavie, J.: Mediastinal endocrine neoplasm in patients with multipl e endocrine adenomatosi s; a previously unrecognized association : Cancer, 29:1075-1083, 1972.

Rosai, J., levine, G., Weber, W.R., and Higa, E.: Carcinoid tumors and oat cell carcinoma of the thymus. Pathol. Ann. (in press, 1975).

Salyer, W.R;', Salyer, D.C., and Eggleston , J.C.: Carcinoid tumors of the thymus. cancer, 37:958-973, 1976.

CIUDAD SANITARIA VIRGEN DEL ROCIO CENTRO DE UHA81U'TACION Y TRAUMATOLOGIA Sevilla 15 de Diembre de 1 . 976

SERVICtO OEANATOMIA PATOLOGICA

SEVI LL A

CASO N2 1, Timoma

It

It

It

II

II

II

It

II

II

It

II

II

II

It

It

II

2, Timoma Linfocitico

3, Ti reoma Mali gno. Posibil i dad como otro di agnostico

Carninoide F~eocelular.

4, Timoma Epitelial .

Timoma Carcinoide

5, Timoma Carcinoide

Carcinoma medular sobre tiroides ect6tico.

Timoma sarcomat6ide

6 , Enfermedad de Hodgkin, f orma esclerosie nodular.

7 , Linfoma linfocit ico difueo .

8, Timoma

Carcinoid a

9 , Tumor de Seno endodermal .

Mesotelioma

10 , Timoma

Carcinoid a

CONFERE~CIA SOBRE "EL TII•\0 Y EL SISTEMA INMUNOL6GICO" Y SEMINARIO SOBRE PATOLOGIA DEL TIMO

DR. JUAN ROSAI

Profesor de Patolog1a y Director de Anatom1a Patol6gica, Escuela de ~~dicina de la Universidad de Minnesota, Minneapolis, Minnesota, Estados Unidos.

Sevi 11 a, 15 de enero de 1977

' ' DIAGNOSTICOS Y BIBLIOGRAFIA

' EL TIHO Y EL SISTEI1A INt1UNOLOGICO.

Adams, J.E.: Leukemogenic thymoma; Report of a unique case. Am. J. of Clin. Pathology, 40:173-182, 1963.

Alpert, L.I., Papatestas, A., Kark, A., Osserman, R.S., and Osserman, K.: A histelogic reappraisal of the thymus in myasthenia gravis. A correlative study of thymic pathology and response to thymectomy. Arch. Pathol., 91: 55-61' 1971.

Ammann, -A.J., l~ara, D.W., Salmon, S., and Perkins, H.: Thymus transplantation; Permanent reconstitution of cellular immunity in a patient with sex-linked combined immunodeficiency. N. Engl. J. Med., 289:5-9, 1973.

Appel, S.H., Almon, R.R., and Levy, N.: Acetylcholine receptor antibodies in myasthenia gravis. N. Engl. J. 11ed., 2-93:760-761, 1975.

Bearman, R.t~., Bensch, K.G., and Levine, G. D.: The normal human thymic vascu­lature; An ulstrastructural study. Anat. Rec. (in press).

Clark, S.L., Jr.: The intrathymic environment, Chap. 4. Thymi c Dependency. In: Contemporary Topics in Immunobiology, Vol. 2 (Eds.) Davies, A.J.S., and Carter, R.L. Ne1~ York and London: Plenum Press, 1973.

Conference: MYastenia gravis. Ann. N. Y. Acad. Sci, Vol. 274, 1976.

Conference.: Thymus factors in immunity. Ann. N.Y. Acad. Sci., Vol. 249,1975.

Davies, A.J.S., and Carter, R.L.: Thymus dependency. New. Y,ork , Plenum Press, 16:368, 1973. .

Fisher, E.R.: Pathology of the thymus and its relation to human disease, pp.676-729. In: The thymus in immunobiology; stnucture, function, and role in disease. (Eds.) Good, R.A., and Gabrielsen, A.B. New York: Paul B. Hoeber, 1964.

Fisher, E.R.: The thymus, pp. 197-223 . In: Endocrine Pathology. (Ed.) Bloodworth, J.tot.B., Jr . Baltimore: The Williams & l4ilkins Company, 1968.

Goldstein, G., and Mackay, I.R.: The human thymus. St. Loui s: Narren H. Green , Inc. , 1969 .

Hakanson , R., Larsson, L.l. , and Sundler, F.: Peptide and amine producing endocrine-like cells in the chicken thymus; A chemi cal, histochemical and el ectron microscopic study . Hi stochem., 39:25-34 , 1974.

Hayward, A.R.: Myoid cell s in the human foetal thymus . J. Path., 106: 45-48, 1972.

Hwang, W.S., Ho, T.V. , Luk, S. C., and Simon, G.T.: UHrastructure of the rat thymus; A transmi ssion, scanning electron microscope, and morphometric study . Lab . Invest., 31:473-487, 1974.

Jepson, J.H . , and Vas, M.: Decreased in vivo and in vitro erythropoiesis induced by plasma of ten patients with thymoma, lymphosarcoma, or idiopathic erythrob 1 astopeni a ~ Cancer Research, 34:1 325-1334, 1974.

Leckband, E. , and Boyse, E. A. : immunocompetent cells among mouse t hymocytes : ~ ~. A minor population. Science, 172: 1258-1260, 1g71 . 1 1

Levey, R.H. : The thymus hormone. Scientific American, pp.• 2-8, July 1964.

Luckey, T.D. : Thymic hormones. Bal timore, University Park Press, 18:376, 1973.

Mandi , B. , and Glant, T. : Thymosin-producing cells of the thymus. Biology, 246:25, 1973.

Metcal'f, D.: The thymus; its role in immune responses, leukaemia and carcinogenesis. With a foreword by Sir Macfarlane Burnet. York, Spri nger-Verlag, p.l44 , 1966 .

Nature New

development, Berlin, New

Mittag,-T., Kornfeld, P., Tormay, A., and Woo, C.: Detection of anti-acetyl­choline receptor factors in serum and thymus from patients with mYasthenia gravis. N. Engl. J . Med., 294 :691 -694, 1976.

Norris, E.H .: The morphogenesis and histogenesis of thymus gland in man , in which the origin of Hassall ' s corpuscles of the human thymus is di scovered. Contri b. Embryol . Carnegie lnst. (No . 166) 27 :191-207, pl . 1-7, 1938.

Pyke, K.W., and Gelfand, E. W. : Morphological and functional maturation of human thymic epithelium in culture. Nature, 251 :421 -423, 1974.

Raff, M.C.: T and 8 lymphocytes in mice studied by using antisera against surface antigenic markers. Am. J. Pathol ., 65:467-478, 1971.

Trainin, N.: Thymic hormones and the immune response . Physiologi cal Revi ews, 54:272-315, 1974.

Turpen, J.B., and Volpe, E.P.: Ontogeny and peripheralization of thymic lymphocytes . Science, 182:931-933, 1973.

Van Beckkum, D.W., Ed. : The biological activity of thymic hormones. New York , 1975. John Wil ey & Sons .

j

~ STANFORD UNIVERSITY MEDICAL CENTER ~ STANFORD, CAI.D'OIU'-'IA 94!05 • (415) 497-52:52

&lORD U~IVERSITY $tHOOt. OF MEDIClNI

~f o/ P411hOIOJ1 rem, .\I .D., PrD/usor and Choirmon

10 December 1976

Juan Rosa i, M. D. University of 11innesota ~partment of Pathology Schoo 1 of Medicine Iii nneapo lis, Minn. 66455

~ar Juan:

I am sitting at home by a roaring fire lfstening to Beethoven and enjoying the cases that you sent me.

Case 1 is indeed a perfect thymoma. I 1 ike the lyn{Jhocytes particularly, si nee it shows that many of them are "turned on" and mitoses are readily found. It is really interesting how this escaped attention for so many years and even rerited special co111rent in David Korn's article in the New England Journal of 1-edicine. This case shows degenerate ly~hocytes in small cyst-like spaces , 1~hich probably represents what we called (rightly or wrongly) errperipolesis . I also li ke the medullary differentiation of Rosai. I notice ~lith interest the spelling of the co-author of Reference #9 for case #1! Sic gloria transit.

Case 2: Notice the misspell ing on line t~10 of the history ("corticaria"}. Another excel lent seminar case, this one I think showing to good advantage the va 1 ue of mdullary differentiation in distinguishing thymoma from ly!illhOma. I love the tail of atrophic thymus at the periphery and I wonder whether some of the Hassall 's corpuscles whi ch are so prominent at the edge of the tumor represent included thymus rather than actual formation of Hassal 1 's corpuscl es by the tumor. I have this concern in relation to all well defined Hassall's corpuscles seen in thymomas.

Case 3: This certainly seems to be a good exarrple of a metastatic malignant thymoma. ~e cannot but be struck by the numerous lymphocytes in the metastatic tumor.

Case 4: I found this case of particular interest since I have seen extremely few examples of this kind of tumor. The fixation is really beautiful and I assume this was originally fixed in Zenker's or Bouin's. It certainly would have been mst interesting to have had electron microscopy on this one.

Case 5: This one is of course burnt on IllY memory and I can only say I have seen it before rather than I kn011 what it is. Your designation seems to be as good as any, although there is really no hard evidence in this particular case that this tumor has arisen from the thymic epithel ium. The term malignant tt:ymoma sarcomatoid, is perhaps misleading in the purest sense of the word. It seems to rre that minimal criteria for this category should include definite epithelial differentiation as seen either on light or electron microscopy, as well as definite mesenchymal differentiation exemplified by the presence of cross stri­ations. Nevertheless, I know what you are driving at and I don't wish to be too pedantic.

Case 6: Hhile this is a nice exarrple of Hodgkin's disease, I think that it

Juan Rosai , M.D. 10 December 1976 Page Two

would be better to use a case that shows actual thymic involvement, for example, with cyst formation.

Case 7 is really quite astonishing in some resepects . In the tl-tenty-three cases of this tumor that I had the opportunity to review at Stanford, none were in asymptomatic patients. I have seen three patients with histiocytic lymphoma, first detected on routine chest x-ray. I might add that t1-to of these patients did very badly within months to a couple of years. I think the diagnosis .ll. convoluted lyiJ1lhoma as judged by the lYI!llhocyte morphology which is typical . It is interesting that all of our twenty-three cases were convoluted in contradistinction to the appearances of Natwani and Rappaport. I sent all our cases to Dr. Rappaport to see l'ihether he l'ias using different criteria for convoluted cells and he agreed that indeed all of ours 1·1ere con­voluted. Some of our cases had residual thymus as seen in yours and it has been IllY experience, both in this form of lymphoma as v1ell as histiocytic .£..y."l'h---.. and the one case of well differentiated lymphocytic lyflllhOma involving the anterior nediastinum that I have seen, that Hassall 's corpuscles tend to lie preserved in a sea of neoplastic lyl!llhocytes. Not surprisingly, they are resistent to des­truction by the ]ymphoid infiltrate. Obviously, this is a very misleading histo­logic feature and I think it l'iould be quite easy to call a case like this a thymoma, especially given the unusual clinical history for this tumor. There is entrapment (or i.nfiltration) of fat and, although I have previously used this as rather a .good· criterion for lYI!llhoma, I have discovered to IllY disappointment that perfectly bonafide thyn~mas can engulf fat in a similar fashion. This is a fantastic case.

Case 8: This case is especially interesting to me and I have in fact spent most of the day reviewing the Stanford cases classified as malignant lymphoma of the anterior mediastinum. As I mentioned earler, the fact that this patient had a ~ass as seen on routine chest x-ray, is not against the diagnosis of lymphoma. In some of our cases I have been quite unable to make a decision and have been aided substantially by electron microscopy. This has worked in both directions, in some cases showing epithelial features and in others charac­teristics more indicative of histiocytic lymphoma. An electron microscopic feature that appears quite useful in the diagnosis of histiocytic lymphoma is the presence in numerous cells of nuclear blebs. Of course, this is nonspecific and can be found' in occasional lyl!llhocytes in thymomas. Another obvious clue to the "histiocytic" nature of a tumor may be found in the manner of spread. We have been helped in some cases by lyl!llh node involvement or hepatic or other visceral involverrent in a lymphomatous pattern. In the absence of either ultra­structure or patterns of spread, one is really 1 eft 1·1ith a very subjective choice indeed. I have signed out my consults of this kind as~malignant tumor, unclas­sified', rather than atteJ!llting to squeeze them into one or the other category. In case 8 I would have done the same, although I have a very distinct bias here t owards lymphoma. The cells do look ren1arkably noncohesive, nonepithelial and lymphoid to me, and I think this is probably a large lymphoid cell lymphoma, or whatever one of ten names for this that you may prefer.

Case 9: This seems to be a nice exal!llle of endodennal sinus tumor and similar to a fe~l that I have seen over the last year. I notice this is a very large tumor and I would be curious to know whether this pattern was uniform throughout

Juan Ros ai , 11. D. 10 Decenter 1976 Page Three

or ~lhether there 1~ere other areas of embryonal or teratomatous differentiation. I cannot find good exarrples of the hyali ne droplet cells containing alpha-feto­protein, and wonder if it was better seen in other sections.

Case 10: Another beautiful carcinoid! I am ahtays struck by the punctate necros 1 s .

I think that you should have a marvelous tine presenting these cases and that your audiences cannot he 1p but 1 ea m a great dea 1. I '11 write to you and let you know what ideas I have about the short course.

~.t "'"'' · ~ Geral d D. Levine,M.D.

GDL :am1

ru STANFORD UNIVERSITY MEDICAL CENTER w STANFORD, CALIFORNL'\ 94805 • (415) 497·5252

lllD UNIV!RMTY SCHOOL OP M£DICINE ..,., of Pt!tholo17 lii!I,M.D., PrOfUJOr 4qd Clttilrtn4n

10 De cerrbe r 1976

Juan Rosai , M.D. Un i ve rs ity of ~1i nnesota, Schoo 1 of 1-!edi cine Department of Pathology Hi nr.eapo 1 is, Minnesota 66455

Dear Juan:

The material from your seminar arrived today and I am looking fol"\'lard to studying it carefully. I certainly agree ~lith your comment about the difficulty of dis­tinguishing beb1een a malignant thymoma and lyn-phoma. I have also seen a number of such cases and ha.ve had the same difficulty. It is this problem that I want to discuss at the Arthur Purdy Stout Society tileeting. I believe I forgot to mention that Whitey Thurlbeck asked for the Human Pathology paper on recent advances in thymic pathology to be ready by July, 1977. I haven't really given any deep thought to this project as yet.

The ultrastructural investigation of the difficult spindle cell sarcoma you have sent me has proven rather frustrating. I am sending you some of the electron micrographs 1 have taken to date, so that you can see for yourself how nonspecific the appearances of this tumor are. I have three more thin sections to look at . You will have to forgive the 1 abel "rna 1 i gnant thyrooma , sarcomatous" on the electron micrographs. That's not an invention of mine and is indeed a contradiction in terms according to our terminology. Hhat can one say about these ultrastructural appearances? Certainly the cells do not have epithelial characteristics. I saw no well defined desroosomes or broad tonofilaments. The cells did appear to like roaking cilia and these are evident in a number of illustrations, such as ~2429 ·and 22437. In 22431 there is a small aroount of basal lamina in relation to the tumor c~.ll s . This was not a very ~1ell deve 1 oped phenomenon, however. Pinocytosis ~1as marked in some cells as seen in 22437A. Many ce 11 s contained fine filaments which seemed to be nonspecific, although I was interested in one collection of filaments in 22435, which was seen to show some organization reminiscent of sroooth muscle. I will be interes.ted to hear whether you can deduce more from these illustra.tions than I have been able to. Considering that the material was formalin fixed, the organelle preservation is really not too bad and I do not believe we can bl ame any lack of findings on fixation.

Best regards,

Gerald D. Levine.~1. D . GDL :aml

t~lignant Thymoma Sarcomatcus

l'la t ei.' 224 26

Malignant Thymom.1 Snreoll!4tous

Platef.! 22427

2,3GP

•

Malignant Thymoma Sarcomatous

Plate1!> 22428

76-5578

le A

~6-WMI$4 /.2 ')$ s • 15,000

Ma l i gnant Thymoma Sar comatous

Plate# 22429

557B

A

11,000

Malignant Thymoma Sarcomatous

Platefi 22430

4,000

.,

Halignant7Thymoma Sarcomatous

Platd 22431

'

..

Mal ignant Thymoma Sarcomatous

Plate~ 22433

~!alignant Thymoma Sarcomatoun

PlateiF 22434

Na lignant Thymoma Sarcomatous ,

Plate;; Z2435

\

,,

Malignan~ Thymoma Sa~comatous

Platev 22436

• .0

15,000

. .

Malignant Thymoma Sarconwtous

Plate;\! 22437

•

A

15,000

•

. , . . ~ 0

'. . ....

Malignant Thymoma Sarcomat ous

Plateif 22437A

II

• '

·- ----=--:: .--....... -- -

SEMJNARIO S

XXU JORNADAS NACIONALES DE LA SOCIEDAD VENEZOLANA DE ANATOMIA

PATOLOGICA Reuni6n Anuo l de lo Dlvlsi6n Venezolono c!e to Academic

lnternocionol de Med'cino.

'HOSPITAL GE.NERAI. "DR. ALFR~;r,Q VAN CRit.KfN"

Coro- 2.5 al 28 de ~bp II" 1.977

I

~l MINAI! Ill ';liB f<l I Ul~l !I<! ·-) Uf L I h I I I Ulll

c xr~ ·· n •'HJ' ~ ,, ,. A., ,j(,, (,t Pat .. (6 •I lea d~ (r! 11 11 < v~ • ~ <ola d d q llu ~ '" ' ~ A< '~~ ; 1v6~ d<•f Ovptrora ' m .·n ( (• rJ,, /.t ( \_' ·'Lft6 cvp ( a F f,, c t lf6 ""' " v ll ~ f l>e6t i f!lfu Na c <"n a f ,[ ,• M< C1<•bi,.f,•q f a rlv 8 ftf ll <'6 A i

1VA , A~-J"'(<na.

Cnr o , VdnPzuela , mayo 1977

<:A SO 1 ( // R/6 · 555 ; (.tH t e s fd d e l Or . Ron a ld -L . Vi ll e ll a, Me r c y Ho,p it al , Mi nn e d po li s , 11in ne ><>ta ) . Ho mb re de 31 a~o' a 1 qu e se I e prac t i c 6 o r qui e:<. t ,J rni a rddlcal i z quier-da po r t umo r . En el -a l\o 1962 hal>ia re c.. i b ido radi ot e r ap i a pu r re t i cu l o o;A r t.nma de ga n g I i o~ I in felt icos .

CASO 2 ( BH /( 73 - 3864) Pac ien r e de 6 2 a il os , -qui ~n de,de ha c ra ~ inc 0 mese s no t a ba una ma~ a f i r me e n e 'l t t: ":ot i ..,. ul o d e re<. ho q u e dup l i c. aba ~u t a ma :­fl o . £ 1 Dil< i en te n .,g6 perd [da de p e s o , d o l or o ­malt: St or a soc i itd O c.. on e l t umor . No -.e a prec iaba ­qin ~ ~ nmdsr i a. AI exarnen ff s i 'o ,e c o mprob6 una -m.:t, d intra tec.ti l.u l ar de ~ x q e m, du ra , f i r me y-nf) J(• l ,. , ,, so. f l epid idimo se p;alpaba netamen t e . Se V' "' ti c 6 o rqui ec t om la .

C ASO 3 ( BH #7 3 · 999 3 ) Paciente de 52 a n o s -qu e req u i r t o cun$ ul tA en a 9 o st o de 19 73 po r tu-­nl ( ) t e n te s t l e u l v der ec ho . Se p r ac. t i c6 or quiec t o m i c:~. f ,, oc tub r e d e e s e to ismo aiio fu e 'S u me tido a 7

l ln fa d f' n e ct o rnl a re 1 r •lP"" ' i t ooea l t> il t1 t er dl o;e gui ­d~ d P ~1u i m i 0 1 e r ;ap l ~ du r rl nte un la p ~n de d<)~ a ~ n~ .

~ I p M f i t'" n I ~ n (' f> "t I a f t" I i b i e n d I,. I n j f'l q tin t (' a I am i e n -' '' .• n 1.:. dl r ••.-i l i c1 ad

Cl\SO 4 ( f/7 6- 1 3 4 7 ; cortes i a de I 0 r C a rn i I I u Bologna, Ansgan Hospital Minnesota) . Hombr e de 24 alio s con tumo rac l6n en· test i cu lo i zqu ierdo.

CASO 5 (BH #72-11575). Nino de 17 meses con aument o de tamano de te sticulo der echo desde que -ten ia tres meses de edbd. Se practic6 orquiecto-­mia r adical izqul erda.

CASO 6 (BH #72-4306). Hombre de 30 ali os con una ma sa e n test fc ulo Izqu ier do . Se pr a ctic6-o rquie c tomia.

Cl\SO 7 ( 117 6- 1 1 8 2 ; cor t e s i a de 1 0 r . P au 1 E . Nord li e, St . Jo seph ' s Hospital, St . Paul, Minneso tal . Pa c iente de 32 anos , al que se l e encontr6: un tumo r en el te st iculo derec ho. Se p ract i c6 or­quiectom ia c on 1 infadenectomia re troper it oneal .

Cl\SO 8 ( K7 2 - 1 1 6 9 8 ; co rt e s ( a de I D r . H . R a -veto Barre, Laboratorio Na cional de Sal ud Publica, Republica Dominicana) . Hujer mestiza de al red edor de 60 alio s de edad, qu len refiere que desde ni lla -not aba una t umuraci6n tota lmente indo l ora y asinto matica en I a r e gl6n in guina l de re cha. La tumora-: cion f ue creciendo con Ia edad sin que trajera apa rejada molestia alguna. Las relaciones sexual e s: s lempr e fueron norma le s. Reclentemente s uf ri o un ­go l pe so bre Ia tumoraci 6 n con agudo dolor. Lo que ­la 1lev6 a Ia consulta m~dica . En el examen se -­comprob6 que Ia tumora c16 n tenia el tamai'io de una­per a y e ra m6vll y dolorosa. La micci6n y def eca ­c l6n eran normales. El cl itoris e st aba bien con-­formado pero estaba algo agrandado. En e l examen a l ra ves de Ia vagina no se palparon utero ni ane xos, io que se conflrm6 en una laparatomia explo radora. la s mamas mostra ban desarrol lo normal .Se e xtirp6 Ia tumoraci6n.

2

CASO 9 (#7 3 -IIS 3~; LOrtes fa de I~ Ora. Eu-

gen ia Parke r , John Cochran V. A. Hospita l, St . • J. Louis, Mi ssouri). Ho mbre de ]I a lios que in g resa a , 'I Ia consulta por masa en el testi c ul o derecho ac om- · pa~ada de dolor que apareci6 cuatro dias an te s de-su admis i6n en el ho spi tal. Entre l os ante c eden-­tes y figura prostat ec tomf a a los 61 a~o s y padecl miento de ulcera de duodena y disnea de esf ue rzo,­de sde hace vari os a ~os se practic6 orquiect om fa de rec ha.

CASO 10 ( 6 7 6- 1 1 8 7 ; co rt e s r a de 1 Dr . M . P a s -culll, Sa natoria Pu ey rred6 n, Ma r del Plat a , Ar -­gentina). Homb re de 82 a~os. A los 73 aiios fue -­operado de adenoma de pr6stata. Reingres6 a los 77 aii os c on re tenci 6n urina ria comp leta, c omp roband o se g ran tumo r prostatico co n c arac tere s de ca rcino ma . Se trat 6 con estr6genos y dilat a c iones uretra l es. El tumor disminuy6 notabl e mente de t amai'io, -con fran ca mej or fa del est ado ge neral. A l o s 81 -aii os el pacl ente present6 aument o de ta ma iio del he mi esc rot o Izquierdo, que s e i n terpret6 como epi dT d[mitis co n reacc i6n de Ia tuni c a vaginal. En vis7 ta que Ia tumorac i6n s eguia aument ando de t amaiio, se ope r6 a los 82 an os, hallandos e un tumor qufs ­ti co de aproxima damente ~ e m de diametro. El pe7-rfodo po sto pe rat orlo tran sc urri 6 0orma lment e. Un ­ano despues el paciente segufa bi en sfn recid iva­local y sin si gno s de meta s tas is. Los preparados del s emin a rio co rresponden a Ia tumoraci6n qufsti­ca tes ti cu lar .

CASO 11 ( H R 7 6 - 1 ~ 6 2 ; co rt e s T a de I Dr . H a r lan Spjut, St . Lu ke' s Hospital, Houst o n, Texa s) .­Hombre de 42 a~os de edad con dolor test i cular de do s meses de evol uci 6 n. AI e xa men fisi co s e encon r r 6 un tumo r de IOxS em , li so , firme y libr e onent e movi ble en e l testi c u lo derecho. No ha bia antece dentes de fi ebre, sud~ re s noctu rno s. perdida de7 pe sc) o ano rexi a.

3

CASO 12 ( 8 1\ 7 5 - 8 4 0 ; co n e s r a de 1 0 r . Gene H . Moore, Penrose Cancer Hospital, Colorado Springs, Colorado) . Hombre de·ZS a~o s de edad. Evoluci6n­de I ~ enfe r medad: tre s semanas. Comen<:6 con s fn­tomas de epididlmltls aguda que no respo nd1 6 al tra tamlento. AI , examen fTs ico se e ncontr 6 una masa en testiculo de recho. Se ~ractlc6 orquiectomla.

SEMfNAR IO SOBRE PATOLOGJA DEL TIMO

Dr . Juan · Rosai, N.D .

P~o 6 e~o~ de Pa~o!og f.a ; 0~ ­it.ec.:to!t de Ana~o11r-i:a Pa~ol6-g~ca U rr <.v e Jt~.t.~y o 6 M~. ,:rne~.o ~a Med~cat Sc hool Ml~ n~ip~ li~, M~nne 6ota . -

Cora, Venezuela, mayo 1977

CASO 1 (/IR75-1514; corte s ia · del Dr. Thomas R. Hallin, Methodist Hospital, Minneapolis). Hom­br e de 66 aftos con histor i a de miasten i a gravis -­por seis anos, aparecida luego de una apendect?-­mla. Los sin t omas principales eran diplopia, pto­s is bilateral y dific u ltad a Ia mast i caci6n . Una radiograffa de t6cax reciente mostr6 una masa de 6 em lo2alizada en mediastino anterior. Las pruebas de laboratorio eran normales. Se efectu6 toracoto mia, encontrandose un tumor encapsulado cuya par= te pos.terior estaba adherida al pericardia. Habia tambiln adherencias fibrosas ent r e pulmon Izquier ­do y pared costal.

CASO 2 (#UH75-2533): Mujer de 25 alios· con -historia ~e tos cronica y urticaria. Radiogr•ffa de t6rax revel6 una masa en mediastino antero•~pe­rior, que fue ext i rpada en su totalidad. El as­pecto macroscopico era el de un tumor encapsulado­de 9x8x5.5 em. La superficle de corte era solida, homogenea, de co l or blanco grisaceo. Las la·mini lias del seminar io corresponden a este tum·or. A-­los o c ho meses de Ia operacion" Ia enferma consul to ' por recidiva de Ia urticaria. Linfanglografia ret roper i tonea I demostr6 gang I ios agrandados, in ­terpretados como sospechosos de I infoma.

CASO 3 {KR76-91; c;ortesia del Dr. Richard J. Reed, Tulane.Univer s ity. Ne w Orleans, Louisiana). Hombre de 53 ano s con historla de tumor med ias tinal extirpado en 1968. El tumor re c idiv6 l oc;almente -­unos a~os despue s y apar ec; i eron metasta s is a dlstan­c; l a que ll evaron al fa ll e c;imiento d e l enfermo. En­Ia autopsla, se encon tr6 re c idiva ma s i va en region­mediast ina l y me tast asis en higado y hueso s. Las Ia minlll as d e l s eminarlo c o rres ponden a l a s meta s tasi-; hepaticas .

CASO 4 ( R76-1369; c;ortesfa del Dr. John W. Te mpl eton, St. Joseph' Hospital, Mem ph is , Te nnes-­see} . N l~a de onc;e anos c;on si n tomas de disnea y -opresi6n re troeste rn a l d e co rta duraci6n. La radio ­g raf i a d e t6ra x demostr6 una gran masa en medi asti -­no anterior, de Ia que se tom6 una genero s a blop s ia

CASO 5 ( R 7 6 - 1 3 6 3 ; co n e s i a de l D r . Wa y n e - -Cha dbo urn, Me tro politan Medical Cente r , Mlnn eapo- -1 is). Hujer de 67 anos con tumo r en medla st in o ante r os uperior. A Ia operacl6n, s e en contr6 una masa s61 ida de 15 em de diametro ma ximo . con area s de in vas i6n pulmo na r.

CASO 6 (#UH74 - 4212): Nina de tre c e anos que­a cude a I a consulta por s en saci6n d e opresi6n retro ­es t ernal. La radiograffa de t6rax muestra una gran­mas a mu l tllobulada ocupando mediastino ante r osupe -­ri o r. No hay evidencia 9e adenopatla ce rvi cal. -Se ef e ctu6 t or a co idml a, en cont r ando se un t umor mul ti : nodular en Ia region t i mica. Una reseccion parc;ial fue 1 l evada a cabo, s eguld a por un c ur so de r ad i o­t e ra p ia.

. ' CASO 7 ( R 7 6 - 1 2 1 9 ; co r t e s i a de 1 D r . N i k o 1 a -

Kos tl ch , Northwes tern Hospital Hi nneapo t fs). Hom -­br e de 24 ano s, aslntomacico, con ma sa en medias­ti na anterosuperio r encontrada e n radiograffa de ru t ina. A 1a op era c~6n . se encontr6 un tumor apare~

6

temente enca p su t~do, qu .. fue fa<ilmente e " tirpado.

CASO 8 (R7 6 - 355 ; corte< fa de I Dr. F. J. Ma r t f nez Te ll o, C i ud a d San it ar i a 12 de oc t ubre, M~ -~ dri d , Espa iia). Mu j er de 24 anos a Ia que se descu brio en r adf og raffa de torax de r u tl na una ma sa ~n7 med iast ino ant e rio r . No ha b f a si n toma t ol og fa pre -­v ia . La pie~a macroscop i ca cor r espon dia a una t umo rac ion de 10 em de dlame t ro, que era b i en delimita da sa l vo en una zona e n qu e i n f iltraba e l pulmo n. -No ha bf a e v i de nc i a de a den opa t i as me dia s tfni c as.

CASO 9 (IR76·231; cortes fa del Dr . Rober t -'W. Webe r, USA F Medica l Ce nter, Kees l er Air Fo r ce­Ba s e , Mi s s i ss i ppi ). Ho mbre de 19 anos co n gr an rna­sa tumora l en me di as tin o an te rosuper l o r , si n e v i - .. dencia de metasta s is a distancl a . El tumor f ue e x ­t i rpado. Pesaba 400 gm y med(a 12 x8 x6 em. Est.aba­enc a psu l a do y te n fa una s uperfic i e de cor te so l ida , de c o l o r g r i sac eo y mu l ti pl es area s de ne cros is, he morragla y dege nerac i 6n qui st i ca. La con s i stenci a­era blanda.

CASO 10 (R76 -1291; cor tes f a de l Dr . Thoma s Swa llen, North Memoria l Hosp i t al , Hinneapoll s).­Hombre de 35 ali'os . En oc t ubre de 1975, un t umo r ­bro nquial fue e x t i rpado y dlagno s ticado como un tu mor c arc inoid e. Un ano ma s ta rde p res enta una ma 7 sa med i as tinal de 6x 3x3 em en medl ast ino ant e rosu ­pe r ior. Examene s de la boratori o demos t r a ron el eva cion pers is tente de calc i o serlco y hormona pa rat T r o idea, as oc i a das con d ismi nu c i on del fo sforo . La ma s a mediastfha l fue e xtirpa do y el c ue I lo fue e x­p l o rado. Se encontr aron t res g land u la s parati ro i-dea s agrandadas; dos de e l las fueron ex tirpadas . las l am ini li as de l semf nari o co rre sponden a l t umor medi ast inal.

7

CORTESIA 08 LA UNIDAD DO(:I'.NTf: Y DE INVESTrGACION

I

l5l1 SUFtGiCAl PATHOi."OGYuu LABORATORY REPORT 11.75-1514

S£~ 16UROEON

I'OA.Tit

12-1!.-75

li :Sl'OR't: 6E··year··oltl n\Lile >tith ~ lu.story of myasthen. a ~ravia .<:. ~ n twnor of cr ol!!">ter-Lot <OOdiG~~inun• lo.~l[ ch "'l';ighed !.60 gUI. and m(lc;ll.tl1:ec! iO X s.) .. 5 e UI . It had 0

lobular~-~Xtl!o:or.al configuration anli e flesny lobul.~r t an cut ·•uru.~e . At c:..'l.e time of surgery , the tu=r waa noted to l>e close to !·. ut not gros. l ~ : nvacing ch• pe:· icardium, and was not gros&l:, i nvad i ng pleura or lung althO\£;; ~ t:he:-e •••~ s !'ill£ adhesion of th~ indurated long t is6ue to the tumor.

GROSS: A total of fif "een slides labeled 075-9951 ar e aub~tte~ i~rm the Methodist Hospital i& St. Louis Park, Minnesot~ . The slides ere sublabelec ~g follo~: -c, b'.Oj>BY of ante..-ior l!".ediastinal tumor; -D, me<!is ati nd tUII!Or: -:n and -DZ, pe~icardial surface- of the tumor; -DJ, anterior surface o"f -=•-; -P4 a."l<l -n5 , left side of tumor; - 06 and ·-D7, right aide of tumor; -D!l, superior por tion ·o J: tumor; -D9, inferior pct· tion of CUJ!Iot·; -F, left lung tissue .

-c:: MICROSCOPIC: Sect ions show vaacu!ar lymphoid tissue C.""'i>osed predominantly o: ll1Will benigo appearing 'lymphocy t es , However, hiddeu i'l! the baci<ground are &liiAli. ~lueters of epithelioid cella such as those seen itt the thl'!llus . Ha.uall' s corpuscles are not seen in the s~ctions. Sections - Dl ano -02 again 'how · .w ~ncapsulated lymphoid neoplasm directly abutting agains t fibrof~c :y soft tiasue, inte rpreted as pericardium, ~~thout invading it . The neoplas~ i s composed pre­do:ninantly of small benign appE-aring lymphocytes. Ho.,-ever, again (as noted previou·sly) i n the background theTe are numerous clusters of epi.thel i oi.d cells such as those ee~n i n the t hymus. flaaaall 's co..-puscles are not i dent i fied. Ho.reover, the neoplasti c cells are divided into large lo!:mlu by dense hyelinized fibrGUs oa~da. The remainder o£ the &ec tions frc~ the tumor ~-D4 , -D5, -n6, -D7, -DS , an~ -c~) show· a s~GJ.ilar hiG tr•logy. Sections --F sho"' res i dual stropr.ic: thymic tiuue in oi.: ect continui ty with subjacent pulmonary tissue which shows marked interstitiaL !:.brosis, peribronchiolar chroni c lymphocytic infiltration, foreign body gre.nu­lcmas -.•it:h cholesterol clefts and organizing intra-alveolar ncidophilic mat.erial. Ih~re is no evidence of involvell!ettt by the th)'lllic process. The b~stologio f eatures 1 j aeeu in the lung are those of an organizing pneumonic procese. \Lin/Roaa i)

0!/1GNOSTS: Soet tis Rue, anterior u.ediuti num, exci:d.on - Thymoeo. B3Cl-8841A

l ,!N:tlg l ':!-9 12-l.O

'l'hOIIllln a. Ballin, M.D. Pothoiogy Mr.-ti.c.di st l!o6pi t al .; :.oo l:::•cehi or 'B l'ld. Sc. Louis l'R~k, !·lN 5.5426

OlkE.ft P .t. THOLOCY NO.

ollroi'-'IUNOFl..

D COLO!rt 0 8. W PRINTS TRANSP.

JrAN ROSAI , M.D. SPECIMEN IN ~C. PORT OUT

- P"G£

I

ethodlst Hospital 6500 EXCELSIOR BOULEVARD . sT. LO UIS PARK. M INN. 55428 . TELE. 929·13'3

SUMMARY OP HISTORY

Rudolph A. Johnson 075-9951

This 66-year-old white male was round to have myas thenia gravis following surRery for ruptured appendix in 1969. At that time, his primary difficulty was dyplopia and bilateral ptosis, and weakness of the jaw during meals. He was not limited in exercise ability and bas been on Mytelase, 10 mgm., t.i.d. He had also been on Synt heroid, . 2 mgm . daily following a diagnosis of hypothyroidism 1 year ago .

A recent chest x-ray showed a 6 em. mass located in the anteri or mediastinum. He had no symptoms of dyspnea.

Admission ~Abo~apory data includes: 12,400/cu. mm. with 51% neutrophils Profile (SMAC) was normal.

Hemoglobin , 14.6 grams %; WBC count, and 36% lymphocytes. A Chemistry

At left thoracotomy, no definite invasion of adjacent structures by the tumor was noted. The posterior aspect of the tumor vas immedi.ately adjacent to the pericardium, but not apparently invading it. Pleural adhesions of a portion of the left lung to the chest wall were present, but not grossly invaded by the tumor.

ms 12-26- 75

T. R. Hallin

~

~ .. - .. ·-----;~-~-.,.~.,~ ·!'"-·- -.._- -'": . "'-· ...:-"- 7'

> T '

SURG , PA TH, NO,

I rn SUR'"GiCALPAiHOtOGYU~· \;Ill LABORATORY REPORT R76-9l

81RTHOA T£ SUR OltON O,_Te STA T I ON

1/21/76

HISTORY: ~ale pati~~t ~~o had a diagnosis of th;~omn in l 96S ~r 1969 . An au topy was V"rfomed <I t the Chari ty Hospital ir. New OT:i .aane , t,ouis i apa. Netastatic tumors Will'\!! found in the vertebral colullll1 and in the li.ver .

GROSSI Tisaue la~eled A72-759 is submi tted for examinati~n. I t eonsis ts of five frapents of live r, the l ar ges t of which measures 8 em. in ..:ucimum diaenaiop.a. Multip l e grayish-tan nodules are vreaent within the livd~, the largest of which 111eesurel! 1 . ; em. i n. ~~~&Xi arum dimension. The nepatic parenchyma is g1·eenhlt . in color. . Abo submitted i s a portion . of vertebral boar, n1euuring. 2 . S x 2.5 r. 2.0 em. On &ectioning, the bone h!ls a unif.oro light br_ownish-tan co16r ' without any visi ble t:umQr noduJe..s . A leo suhmitte<i ara ~ i'r~egulc fras;v,eo.te Q!· · pul~:~onary t iss ue which &re ateleetstic with focal n.odular i..ndt:Nt i ona. S<m~e of the r.odular a.rees have a W.ic\ eh color, with bulging above the cut surface. Cronly,­this baa the 4!-.Ppea:ranco of bronchopneumonia. On &lec t i on:i.ng, s ome _pf. the ~;mall ­bronchioles appea·r ~o ·be filled <O,>i.th grayisb-yel.lo•N purul.e.nt -plugs , -Sections are submitted aa follows : -A, liver; - il. ver tebral body; -c, lung. C::rar 2) ( I.i~J;·

~ - ~~~

" ' MICROSCOPIC: Sections of 1ive r show numerous metaatati e t:Ul<Or nodules' C01!1Jloaed ·of· l arge sn~ets of ep~thelioid cells admixed with fo&mf hietiocyt es , a few lympho~ : cyt e a, _:ana plasma ce lls. The .epithelioid cells have roun-d to ovd r ather u11ifoiia nuclei with i nconspicuous s111all b asophilic nucleoli and a oderate ~amounts of" acidophilic granular cy toplasm. Rare mitose.s are seen in the sections, w:i thou(. atypical fo1~s. The cumor nodules shov fecal necrosis . ~e capsule of th~ liver· ahous 1!!8:-ke d fibrous thielter.i.ng ri!:h entr apll'.ent of eb:ophi c: hepatic patenc. hymal­tiaau~ an~ bile ducts. Th& bistol ogic appear3nce ia consi stent with metaat3ti~ trullienant epi thelioi d thymOIUa. Se.ctionf of the vertebra show patchy replacement of . the bone l!ll!ri.'OW sp ace by a neoplasm whi ch it composed of a mixture of cell.s similar . · to those ·seen in the· liver. The bony tu!Jecul'ae ahow no pathological changes • • Sections · of lung shcwnumer ou& dilated b ronch i oles f il l ed with purul ent debris ana. murlted squamous me taplasia of the bronch1.11l epithelium. The adjacent pulmonary ' parenchyma shows Qtelectaais, f c;al fibrosis, and organi~ing pneumor.i.a. !here i s no evidence of metastatic tumor . (Lin/Itosai)

~

DIAGNOSIS: Livor ;-autopsy - Metar,;tntl ..: :nallgnan::: thyn1ottlCll . . . . 560o-80l6(980D-8583){3)

Bone, vertchra l body , autopsy - ~tas:atic malignant tb~. 1143-8016(9800-8583)(3}

Lung, site not statec! , autopsy - llroneb,pMut;.t>nia , 2800-4001(3) -

ALl slg .• 1/ 30 2/1.

~ichard : . ~eed , ~ .D . Dermatol ogy P&thology l.abor~tory 1430 TulanP. Ave11•;e Nev Orlenns , LA 70112

E.M. N UM8Cfll 0 X-AAY(I)

'

·. SPECIMEN IN AS.POAT O VT

OIMMU N OP'L o ···" n 8 .. 'W PAINTS

.ta•

...... ~t ...

/ ~~.J

~ !UDE CHILDREN'S RESEARCH 1: :)SPITAl.-Ill L•tld<•rdal~. P.O. /Jox J18, is. TMn<><sec J8101 l5-8J81

r TitOII'k'lS. Founder

Lauren V. Ackerman, H.D. Professor, Department of PatJ!clogy State University of New York at Stony Brpok

Stony Brook, New York 11794

Dear Dr. Ackerman :

September 7 , 1976

•

Re: Lee Ann Oglesby, 11 yr. W-F our ace. no. 576-348; S76-534

We in Pathology ansi the attendant clinicians would greatly appreciate your review and opinion in this case. The patient presented vith a lar ge anterior medias t inal mass which was biopsied (576-348) i n another institution (May, 1976). Fixative ,;.as not formaJ;.,but one found suited to lymph nodal tissues by the pathologi~ts there . Stain was a modified Giemsa. We borrowed the paraffi n blocks and performed. H&E stains which were disastrous . Two referred sections and the latter are enclosed. U1e referring diagnosis was mixed cell thymoma. We consulted with Dr . Benjamin Ca stleman who concurred and the patient was handled as a malignant thymoma.

In July , evidence of widespread abdominal metastases occurred and, at laparotomy, gross tumor was f ound in both kidneys • the r ight ovary and the· mesent ery. No gross or microscopic tumor was found in the liver. H&E and some unstained sections of the se tissues are enclosed (576 -534) . Because of (1) the unusual behavior if the tumor is a thymoma, and (2) the fact that we've never seen a thymoma in the pediatric age group at St. Jude' s, we in Pathol ogy and the involved clinicians would deeply appreci nte y our reviewing th is case.

•

...

Dr. Lauren Ackerman Page 'hlo

• Thank you for your help in this case as well as for y•our invaluable assistancP. over the years.

•

. . ---·

WJ:jd enclo&uJieS

Sincerely,

Warren W. Johnson Pathologist

Department of Pathology School of Basic Health Sciences

HEALTH SCIENCES CENTER State University of New York at Stony Brook Stony Brook, New York 11794

~ 516 444-2185/6/7

Dr. Juan Rosai University of Minnesota Hosp~al Surg1:cal pathology Box 76 M:Lnneapol1s, r~. 50455

September '14, 1976

! Re: S76-348, 576-534, Lee Ann Oglesby ~ 1'\Y case fJ CS 76-486 , •

Dear J uan:

You can see that pr.. castleman has seen the above ref'er-enced case. I have enclosed a cbptf df Dr. Johnson ' s l et ter to me, arid I would Uke to have you write y.ouYOp1nion and send hiln an answer, with a copy to rre . You don't need to .return the s lides .

lolany thanks. 1-Tith kindest personal regards,

LVA:rm unn:..,n V. Ackerman, M.D. Professor of Pathology

i

,

Sl JOSEP.-t riOSPrfJ.\l EJ.\SI _li'_I_C_, __

Juan Rosai, M. D. Director of Anatomic Pathology University of Minnesota Box 76, Mayo Memorial Building Minneapolis, Minnesota 55455

Dear Dr. Rosai :

September 28, 1976

Enclosed are three (3)~ixed blocks on the malignant thymoma that you requested.~

We appreciate the opportunity of sending these to you and sharing this case.

If we may be of further service, please feel free to call on us.

Sincerely,

~~n, M. D. Pathologist

JWT:jh

5959 Park Avenue Memphis, Tennessee 38117 Reply to: P.O. Box 171247 Memphi•, Tennessee 38117

RIS!ORY: ~~7-year-old et~l t~r, with areas of

~ """ .... ' GROSS.l ~o: olide& labeled

em.) anterior euperio~ ~edia-

T

~--·~·-.r,..-- ,.. _..,.,., _ - - ... •

T

l5il SUR&GiCALPATHOLOGfA~$ LABORATORY REPORT R76-12l9 UNKNOWN

HISTORY : wh1.ch was stinotomy. time.

r 7A TION

24-yesr-old male with an asympt omatic aut e rosuperi.or media s t i nal mas s completely encapsulated a nd easily r emoved by the surgf.on a t m<!di s ­

There i s no evide nce o£ systemic dis~ase i n this pa t ien t at the pr e sent

GROSS: One microscopic elide labeled 076-3715 is submitted frolll Dr . Ni kola "Koa t ich of the Northwestern Rospital in Minneapolis, Minnesota. Tb e slide is re t ai ned .

7

MicRoSCOPIC: Sections reveal thymic tis sue with numerous llassall' s corpuscl e s . Porti~! of the thymic tissue ~ the "periphery of the lesion appear to be hyper­praatic, but " are not involved by this malignant process ~<'ilich is present in the majority oi the ~lleue ~n the sectioqs. Most of the th~ic parenchyma is replaced b~ a tlimar COlllpoaed of· highfy .. atypical small to medi-um-sized lymphocytes which · infiltrate in a lobulated fashion throughout the th)'lllic parenchyma. The tumor is not dividedjnto lobu~es b~ dense fibrous septae as seen in most thymomas of the lYlllphocytic. type. ·No perivascular spaces are present and few or no epithelial elements are noted in this tumor . The tumor is infiltrating the surrounding fibroadipoae ti .. ue as -well . The cells are highly atypical, with hyperchromatic and convoluted nuclei. Occasional prominent nucleoli are noted in these cells. Numerous mitotic figures are preaent throughout the tumor. The lobulated pattern of growth Of this lymphomatous process within the thymus is quite str iking; and the irregular lobules of darker staining cells are differentiated fl:·om the adjacent lighter staining areas only by tlte number of cells present. The cel l type appears t o be the same atypic"al proliferating lymphocytes throughout. ln one area, a Sll\811

uayelinated nerve shows fnfiltration of the endoneurium and pe.rineurium by t hese abnormal lymphocytes. No necrosis or giant cells are noted wi thi n the tumor. (Rapke/~osai)

DIAGNOSIS: Thymua, excision - Malignant" lymphoma, poorly differentia.ted lympho-

MH:slg 8/20 8/20

Nikola Koatich, M.D . Pathology Northwestern Hospital 810 E. 27th. St. Mpls . , MN 55407

OTMER P A.THOL.OGY NO, E. M, NUM8C!R

.. OIMMI.,$NOFL..

COLOR

cytic, diffuse. · 980Q-9633(3)U

JUAN ROSA , H.D.

0 X -RA Y(s)

$PG:<: IMEN IN REPORT OUT

B. W P RINTS

•

~; .

Dr. D•F.J.+Mart!nez Tello Jefe del Servieio de A. Patol5gica Miniaterio de Trabajo Instituto Nacional de Prevision

~MV)

11 de marzo de 1976

Ciudad Sanitaria de la Beguridad Social Madrid

RES su li~0476 NUESTRO #ll.7 6-355

Batimado amigo:

•

El caao del tumor mediastinal lo encontrG bastante dif!cil .. lls evidentte que se origina en el timo y me parece bien claro qua aa i:.rata de· un tumor lllllligno, tanto desde e1 punta de viata citoliSgico como t'pogr,fico . Ki 4iagn5stico di:fer~cial est& entr e lf.nfoma maligno de tip5 linfocttico po_co d;aferenCi~o del timo y timoma malnoo. Yo prdiero el prtm.r diq- .'! • noatico por el hecbo que las dllulas tumorales - . parecen linfoid~ y no . epiteliales y por qua no encontr' en el tumor ninguna caractart&tica qpe sugi-riera tilDDIIIIl, tal como espacios perivaaculares, diferenciaci6n medular, roseau, expac:ioa RBeudoglandularee, gruesoe t abiquea 'fibroaoa, dald ifioca-ci~, etc. Bate enfermo necesita r adioterapia.

Un aUudo cor dial,

Juan Bossi, M.D. Director de Aaatom1a patolSgica

.. •

..

R76-23l dPJmLEY , DRISKLE

Bl~TORY : 19-y(,ar-old ule witll a large entc:rior- superior rr.edi::: t: : nnl lllB89 , There i s no ev idence of primary tumcr elsewhere, and no evidence nf m~tcetasiB . The tumor weighed 400 6'111 · and measured 12 x 6 x 6 em. The t ucor wa& encapsulat ed and the cut surfaces revealed a grayish-,.,bite mottled appearance . '•uC'h of the tumor •·an nee>: otic, and there were areas o.f hemorrhage . A few cystic cavi ties were present, tbe lurgest measuring approximately 2 x: 1 x . 5 em. Generally , the con­s i stency of the tumor was soft and the surface.s were mucoid or slin\)1 in areas .

GROSS: Eight slides labeled 1186 ore oubmitted from the Department of Pathology, U. S.,\. F , Medical Center, Keesler Air Force Base , Mississippi .

HI::ROSC~PIC: Secticn& show a lllllllsnant. neoplasm. with. extensive necrosis. The viable portion is composed of glandular, tubular, and anastomosing channels lined by flattened, cuboidal or tall columnar plcomcrphic epithelial cells . In aome areas there is proliferation of the lining cells, forGing papi llar y intraluminal projections . Glomeruloid atructut·es and Schiller- Duvall bodies are seen fre­quently. Mitotic figures are numerous . The micros copic appearance i s that of an endodermnl sinus tumQr (yolk sac tumor). (Chen/Rosai)

DIAGNOSIS : ~lediaatinum , anterior-superior , excision - Endodennal sinus tumor.

TKC:slg 2/18 2/19

W. Robert Weber, Maj . , U.S .A. F ., M.C. U. S.A. F . ~ledical Center Keesler Air Force Base, Miss . 39534

D I MMVN OF"L.

n RAW ~NIN•Il

Y230-9079 (3)

--zcv JUAN 3.0SAI , M. D.

REPORT

I~ G H.tl ?.Q PI\ \Z: OS

' ' $ V RG , PATH HO.

76-lJ'fi.

~~r'~"J ><Os~ . "1"W'f@;l ~' /0

8 1A:T ... OAT£

1

••• 35

su I.SURG£ 0H

I'OATE l'TA TION

t! 9/3 .1 7 ~

E:;:S1'0RY : 35-yPEa·-old :.u; lp >iT'<. ,_~cprwE> ot le!t opp.-r lo:...-~ cet:::' in OcLobt>r ci 19i f or a bronchial carcinc,id wbic-;. invo1vrd tt.l' bronohus aPe E-: u nd!'d into cht at!jacent pulm011BTY part>nchyliU!. IJ~ alsO hoc; 8 BrfOTl!tl> 6 11" ~ '< J M;J , U:<'~lDStinol mars (N7.5-10230C). Ht' was tht>n nc•tf'd to ~ IJVI' p<->:uis tPn~ly hl.gh BHUOl ca l ciu~' lrvt>le , with low Sl'rum phosphorus and ••lo>VIIt.Pd pllrahormone . At M·Lk P».ploration, par &thyroid glAnde wer" removec! from tht' dgh t l o,...,..r pol~ (N76-894 7ll l und from thE' d ght upper J..>Ol~> (N76-Z947C). h. 0 . 5 cu. purRLhyroia lias sHn s t toP lc•ft upper po lt> , but was not rt>ruoved . The •urs~con di ,i no t i d!'nti £y e left lo• "r gland.

GROSS: Four slidl's (two label ,.d'-' N7 5-10230 aud two lsbt>l<'d N7~9~ 7) arP rl'ct-ivPd from Dr . Swa llen of the North M~>morial Hospi tal in MinneEpolis , kinnl'aota. Th<' slid•• are reta ined.

MICROSCOPIC: St>ctions of t l!c lung show s b ronch i aj- carcinoid i1 volving thP hronchua and extending into th!' adjacect pul monBry pf rencbyoa. This tumor is grcwing pr imarily in a ribbc~1 ike pa t tern, with scan~1 .ri tos<'s. S£ctions of the ~~~ediastinal tamar show a thymic carcine~ma gro~•ing predomi a ,;ntl) in largl' tiolid balls of cells , some of which beve c<>ntrlll punc tate nt>crosis end caldfi cat i on. Mitoses ht'rt are morl' frequent t nan in tbe pulmonary tumor , and the ribbon pattern is not promint'nt. Sections sha- th<> tumor growing around a small isl~nd of thymic tiesue with COI:'tE'X end Hassall' e corpu6Cl l'&. Se ctions of parathyroid show chief cl'll hypt't'plaoie of both glands . Ad ni. tionclly, the> gland from t h• rij;:•t upper pole (~if>-8947C) show£ 11 s;rnll locus of metaRtaric carc i noid t=or with rnsf'ttPs and lt.l.t' t i c fi guree. This bPha\'ior u morP cons i.atPnt: wi t h thP thymic p; im.t ry . The pere:hyroid mHuUsis and bot.'l t h t> pulmonary and thymic carciuo.d~ .lrP r t>pot: tl'rl to l:>P argyrophil poaiti vt>. Thi a c on:bi!'atioa of tWI!O't& i s i ndi::ativt> of a multiple i'ndocrine edt'nomatosis, hut n:~thl'r hiSCO'!')- i£ re«1ui-::t>ci to dP ternine the typl'. {i\isdd 1/Rosei)

DiAGNOSIS: Lung, lt>f~, upper lobectomy- Carc i noid tumor . 2800-C243(3)U Thymus, Pxc i eicn- Ca rcinoid tu~or . 980Q-8243(3 )U Perothyrcic , right c ppPr ~nd lo~Pr, e~cision - ChiP£ cPit bypPr-

plssin. 970G-710l())U

9.JR :slg 9/S 9/10

Dr. S;.-allen Nart.• Mf'mc l'i&1 lloepi tel >.lv lo•ry Avp . N. l!pl~ ., ~JI :>5422

tumor . - MP t astaLic <' >l'C inoid 9700-8016 (9~00 -8243){3)U

~

JUAN ROSAI, H .D . OTHE:A PA T ... OI..OOY NO. e, M, N U M6£R

D X-RAVII ) R I!POI\1' O UT

D IMMUN OF L.

'- '~ n .... ... ............ .

' r. J .. ..;; · ·~