Journal of Surgical Oncology 19: 145-150 (1982)

Oat Cell Carcinoma of the Esophagus

DEBA P. SARMA, MD From the Department of Pathology, Veterans Administration Medical Center and Louisiana

State University Medical School, New Orleans

An oat cell carcinoma occurring in the esophagus of a 59-year-old man is described. A review of another 22 cases of such a tumor from the English literature is made. These tumors may have three histologic patterns: pure oat cell carcinoma, oat cell carcinoma with squamous cell carcinoma, and oat cell carcinoma with adenocarcinoma. They appear to arise from enterochro- maffin cells; the neoplastic cells show argyrophilia and neurosecretory-type granules on electron microscopy. Resection has been the principal mode of therapy. Overall survival for these patients is about 6 months, with most patients dying of extensive metastatic disease.

KEY WORDS: esophageal cancer, esophageal oat cell cancer, oat cell carcinoma

INTRODUCTION Oat cell carcinoma of the esophagus is an unusual and

rare neoplasm. Considerable controversy still exists as to its histogenetic classification, even to its existence as a spe- cific entity. Meaningful information to assist in the clinical management of patients with oat cell carcinoma of the esophagus is not available. The literature contains a suffi- cient number of case reports to permit a comprehensive review and analysis of the lesion.

The present communication is a report of a case of oat cell carcinoma of the esophagus and a review and analysis of 22 cases collected from the English literature.

CASE REPORT A 59-year-old man presented with a 2-week history of

hematemesis and a 20-pound weight loss over several weeks. He gave a history of having smoked two packs of cigarettes a day for 40 years. A lesion in the middle third of the esophagus was found on esophagoscopy, and ex- amination of the biopsy of the lesion revealed small cell anaplastic carcinoma. Examination of a bone marrow biopsy showed metastatic carcinoma. The patient expired within 4 weeks of admission before any therapy could be admin- istered.

Postmortem Examination A 3 X 1.5 x 1.5-cm hemorrhagic and ulcerated mass

was found in the midportion of the esophagus. The tumor invaded the entire thickness of the esophageal wall in an

expansile fashion. The paratracheal and peripancreatic lymph nodes contained secondary deposits, and there were metastases in the liver, adrenals, kidneys, and vertebral marrow. There were two subpleural metastatic nodules in the left lung. The bronchial trees of both lungs were free of lesions.

Histology (Figs. 1-3) The esophageal tumor was composed of sheets of pleo-

morphic anaplastic cells with intensely hyperchromatic nu- clei and little cytoplasm. An alveolar pattern was present in some areas due to fibrous septae traversing the sheets of neoplastic cells. There were areas of spindle cells and giant cells and mitotic figures were numerous. The overall ap- pearance of the tumor was similar to that of oat cell car- cinoma of the lung. There was no differentiation into squa- mous cell carcinoma or adenocarcinoma. No benign or malignant squamous pearls were seen. The metastatic de- posits in various tissues had similar histologic appearances as the esophageal primary.

With the Grimelius silver impregnation method the neo- plastic cells showed intracytoplasmic argyrophil granules, but with the Fontana-Masson method no argentaffin granules were observed in the tumor cells.

Ultrastructural studies revealed extremely poor preser- vation of the morphological details of the tumor cells due

Accepted for publication July 7, 1981. Address reprint requests to D. Sarma, MD, Department of Pathology, VA Medical Center, 1601 Perdido Street, New Orleans, LA 70146.

0022-4790/82/1903-0145$02.00 0 1982 Alan R. Liss, Inc.

146 Sarma

Fig. 1. An elevated tumor mass occupying mucosa, submucosa, and invading muscle coats of the esophagus (H&E, x 10).

to post mortem autolysis and were not considered satisfac- tory.

DISCUSSION The table lists the essential features of 22 cases reported

in the English literature and one additional case report from the present communication.

Definition McKeown (1952) first described two cases of oat cell

carcinoma of the esophagus [ 11. Since then various reports have described this entity, calling them by different names such as “anaplastic carcinoma,” “argyrophil cell carcinoma (Apudoma),” and “small cell carcinoma.” It appears that the following three morphologic patterns are seen in oat cell carcinoma of the esophagus:

1. Oat cell carcinoma in which the primary tumor as well as the metastases show morphologic features like that of oat cell carcinoma of the lung.

2. Oat cell carcinoma with squamous cell carcinoma in which typical oat cell carcinoma is associated with inter- mingling invasive squamous cell carcinoma or intraepithe- lial squamous cell carcinoma.

3. Oat cell carcinoma with adenocarcinoma in which typ- ical oat cell carcinoma is mixed with adenocarcinoma.

Histogenesis Earlier suggestions as to the origin of oat cell carcinoma

of the esophagus included embryonal tracheobroncial “rests” [l], submucosal glands [2], and squamous mucosa [3,4]. After the recognition that oat cell carcinoma of the lung is apparently derived from cells of the enterochromaffin sys- tem, Tumbull et al [S] suggested that similar cells probably give rise to oat cell carcinoma of the esophagus. The nature of the oat cells was further clarified by the demonstration of cytoplasmic argyrophilia [6 ] , the ultrastructural obser- vation of neurosecretory-type granules in the tumor cells (7-101, and the finding of ACTH activity in the tumor tissue by bioassay or radioimmunoassay 171.

Incidence Approximately 23 of these rare tumors have been reported

in the English literature. Most have been reported as single cases, and it is difficult to estimate their incidence. Whereas American authors [5 ] reported an incidence of less than 1 %, Japanese authors [ 111 reported a much higher incidence, up

Fig. 2. Typical microscopical field Showing oat cell carcinoma invading submucosa and muscle coat (H&E, X 100).

Fig. 3. Higher magnification shows darkly staining round and ovoid cells with scanty cytoplasm (HBrE, ~ 2 0 0 ) .

148 Sarma

to 9%. The tumor occurs about twice as often in men as in women, and ages range from 52 to 76 years, with most patients in their fifth and sixth decades.

Gross Oat cell carcinomas are mostly fungating or polypoid

lesions with or without ulceration. Stricture was present in one case. About half of the reported lesions were located in the lower third of the esophagus and the other half were in the middle third.

Microscopic About half of the reported cases showed a pure oat cell

carcinoma pattern simulating that of the lung. The tumor consisted of uniform round, oval, polygonal, or spindle cells with intensely hyperchromatic nuclei. The cells were ar- ranged in sheets; and occasionally rosettes, duct-like struc- tures, or an alveolar pattern were noted. The cytoplasm was very scanty in most of the tumor cells. Occasional neoplastic giant cells were seen and mitoses were numerous.

More than four reported cases showed squamous cell carcinoma intermingled with oat cell carcinoma or intrae- pithelial squamous cell carcinoma of the overlying esoph- ageal mucosa [ 1,3,6,9].

Three reported cases exhibited gland-like lumina con- taining proteinaceous material that stained positive for PAS and Alcian blue in one case [7,8].

Histochemistry The tumor cells were uniformly argentaffin negative

(Masson-Fontana) but contained varying amounts of intra- cytoplasmic argyrophilic granules (Grimelius and/or Sevier Munger) [6-8,101.

In a few cases the proteinaceous material that occurred in varying quantity between the tumor cells and in the stroma stained positively for amyloid (Congo red) [7].

TABLE I. Reported Cases of Oat Cell Carcinoma of the Esophagus

Using bioassay or radioimmunoassay, ACTH activity in the tumor tissues was detected in three cases [7].

Ultrastructure The tumor cells were elongated or polygonal with fusi-

form or irregularly shaped nuclei. There were interlocking cytoplasmic processes between the tumor cells, and occa- sional desmosome-like thickenings were noted. Rough en- doplasmic reticulum was relatively sparse; however, mi- crofilaments and microtubules were abundant. A distinguishing feature in these tumors was the occurrence of neurosecretory-type granules in the cytoplasm. The gran- ules were round, oval, or pleomorphic ranging in size from 80 to 450 nm and had electron dense cores of 70 to 750 nm in diameter usually enclosed by a limiting membrane [7,9,101.

Ultrastructural observations in a case of oat cell carcinoma with squamous cell carcinoma showed features of squamous cell carcinoma, such as desmosomes and tonofilaments, in the tumor cells from the epidermoid areas in addition to the previously described features of oat cell carcinoma in the other areas [9].

The lining cells of the gland-like lumina of a case of oat cell carcinoma with glandular differentiation showed many microvilli but no neurosecretory-type granules [8 1.

Treatment and Prognosis Nine patients had undergone esophagectomy. Two pa-

tients were treated with chemotherapy alone [6,12], and one patient was treated by chemotherapy followed by resection [81.

The overall survival was about 6 months after diagnosis and/or treatment. Twenty-four months has been the longest reported survival period in a patient treated by resection 171. The longest survival period among the patients treated with chemotherapy alone was 11 months [12]. Most of the patients had widely disseminated metastatic disease at death.

Authors1 year Agelsex Locationigross Microscopic Course Metastases at autopsy

McKeown, 1952 (2 cases)

Morson et al, 1972 (1 case)

Tmbull et al, 1975 (1 case)

Rosen et al, 1975 (1 case)

68iM Lower 1/3, fungating

60IM Mid 113, ulcerating

551F ?

551F Lower 113

671F Mid 113, elevated, ulcerated

~ ~~~

Oat cell ca Died 5 days Lymph nodes, liver, after admission adrenal, and bone

marrow Squamous cell ca Died in hospital Lymph nodes with oat cell ca

Oat cell ca ? ?

Oat cell ca

Oat cell ca with squamous cell ca

Died 18 months postoperatively lymph nodes, and pleura

Died on the fifth hospital

Liver, pancreas, adrenals,

Liver, ribs, vertebrae, lymph nodes, and pleura

day

Esophageal Oat Cell Carcinoma 149

TABLE I. Continued

73lF Lower 113, stricture

Oat cell ca and squamous cell ca

Died immediately postoperatively

Died 1 month after diagnosis Died 3 months after admission

Lymph nodes Cook et al, 1976 (1 case)

Matsusaka et al, 1976 (3 cases)

Oat cell ca Liver, lungs, vertebrae, and lymph nodes Liver, lungs, brain, adrenals, and kidneys

Liver and lymph nodes

67lM

62lM

Lower 113, polypoid Mid 113, elevated ulcer

Oat cell ca with squamous cell ca in situ Oat cell ca 70fM Mid 113, polypoid Died soon after

admission

Tateishi et al, 1976 (6 cases)

58lF Mid 113, fungating, ulcerated Lower 113, elevated ulcer

Oat cell caa Died 4 months postoperatively

Pleura, liver, and lung

57lF Oat cell ca" Died 8.5 months postoperatively Died 3.5 months postoperatively Died 8 months postoperatively

Lymph nodes and vertebrae

62lM Lower 113, fungating polypoid

Oat cell caa Lymph nodes, peritoneum, pleura, liver, lung, and kidney Lymph nodes, liver, kidneys, pleura, diaphragm, skin, and spleen

58iM Mid 113, ulcerating

Oat cell can

71lM

56lM

Oat cell caa

Oat cell caa

Lower 113, fungating

Alive 24 months postoperatively Alive with tumor recurrence 14 months postoperatively

Lower 113, fungating ulcer

Imai et al, 1978 (1 case)

60lM Mid 113, polypoid Oat cell ca with glandular differentiation

Died 6 months after diagnosis

Liver, sternum, vertebrae, spleen, and lymph nodes

Horai et al, 1978 (4 cases)

64lM ? Oat cell ca ? ?

54lM 72lM 52lM

Oat cell ca Oat cell ca Oat cell ca

'1

? ?

Kelsen et al, 1980 ( 1 case)

761F Mid 113, lobulated mass

Oat cell ca Patient died 11 months after diagnosis. Clinical metastases to bone

No autopsy

Oat cell ca

Oat cell ca

Died 8 months postoperatively

Liver and peritoneum Reid et al, 1980 (1 case)

60lF Lower 113, ulcer

Sarma, 1981 (Present case)

591M Mid 113, elevated ulcer

Died 1 month after diagnosis

Liver, adrenals, kidneys, vertebrae, pleura, and lymph nodes

T w o cases showed glandular differentiation and an unspecified number of cases showed squamous cell carcinoma in situ of the esophageal mucosa.

150 Sarma

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2. Morson BC, Dawson IMP “Gastrointestinal Pathology.” Oxford & Edinburgh: Blackwell Scientific Publication, 1972.

3. Rosen Y, Moon S , Kim B: Small cell epidermoid carcinoma of the esophagus: An oat-cell-like carcinoma. Cancer 361042-1049, 1975.

4. Ming S: Tumors of the esophagus and stomach. Atlas of tumor pa- thology. Fascicle 7. Washington, DC, Armed Forces Institute of Pa- thology, 1973.

5. Tumbull AD, Rosen P, Goodner T, Beattie EJ: Primary malignant tumors of the esophagus other than typical epidermoid carcinoma. Ann Thorac Surg 15463473, 1973.

6. Matsusaka T, Watanabe H, Enjoji M: Anaplastic carcinoma of the esophagus: Report of three cases and their histogenetic consideration. Cancer 37:1352-1358, 1976.

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8.

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12.

Tateishi R, Taniguchi K, Horai T, Iwanaga T, Taniguchi H, Kabuto T, Sano M, Ishiguro S, Wada A: Argyrophil cell carcinoma (apudoma) of the esophagus: A histopathologic entity. Virchows Arch A Pathol Anat and Histol 371:283-294, 1976. Imai T, Sonnohe Y, Okano H: Oat cell carcinoma (apudoma) of the esophagus: A case report. Cancer 41:358-364, 1978. Cook MG, Eusebi V, Betts CM: Oat-cell carcinoma of the esophagus: A recently recognized entity. 1 Clin Pathol 29:1068-1073, 1976. Reid HAS, Richardson WW, Corrin B: Oat-cell carcinoma of the esophagus. Cancer 45:2342-2345, 1980. Horai T, Kobayashi A, Tateishi R, Wada A, Taniguchi H, Taniguchi K, Sano M, Tamura H: A cytologic study on small cell carcinoma of the esophagus. Cancer 41:1890-1896, 1978. Kelsen DP, Weston E, Kurtz R, Cvitkovic E, Lieberman P, Golbey RB: Small-cell carcinoma of the esophagus: Treatment by chemo- therapy alone. Cancer 45:1558-1561, 1980.