J Cutan Pathol 2010: 37: 1088–1091 Copyright © 2009 John Wiley & Sons A/Sdoi: 10.1111/j.1600-0560.2009.01389.xJohn Wiley & Sons. Printed in Singapore Journal of

Cutaneous Pathology

Anaplastic Kaposi’s sarcoma: anuncommon histologic phenotypewith an aggressive clinical courseAnaplastic Kaposi sarcoma (KS) is an uncommon histologicphenotype of Kaposi’s and one that is typically associated with alocally aggressive clinical course. We report a case of a 53-year-oldhuman immunodeficiency virus-positive male, on highly activeantiretroviral therapy 1 month prior to admission, who presented withfever, cough, respiratory distress, multiple skin lesions and cervicaland inguinal lymphadenopathy not responding to multiple antibiotics.Microscopic examination of punch biopsies from the forehead andchest revealed a spindled cell neoplasm with marked cytologic atypiaand scattered mitoses, features consistent with a diagnosis ofanaplastic KS and confirmed by immunohistochemistry with HHV-8.Biopsy of an involved lymph node also revealed involvement by KS.Despite aggressive clinical treatment, the patient rapidly deterioratedand expired 1 week after the diagnosis of anaplastic KS was rendered.Our case underscores the aggressive clinical course of this uncommonhistologic variant of KS and its recalcitrant clinical behavior.

Yu Y, Demierre M-F, Mahalingam M. Anaplastic Kaposi’s sarcoma:an uncommon histologic phenotype with an aggressive clinical course.J Cutan Pathol 2010; 37: 1088–1091. © 2009 John Wiley & SonsA/S.

Yue Yu1,2, Marie-FranceDemierre1 and MeeraMahalingam3

1Department of Dermatology, Boston UniversitySchool of Medicine, Boston, MA, USA,2Tufts University School of Medicine, Boston,MA, USA, and3Dermatopathology Section, Department ofDermatology, Boston University School ofMedicine, Boston, MA, USA

Meera Mahalingam, MD, PhD, FRCPathDermatopathology Section, Department of Dermatology,Boston University School of Medicine,609 Albany Street, J-301,Boston, MA 02118, USATel: 617-638-5574Fax: 617-638-5552e-mail: mmahalin@bu.edu

Accepted for publication June 19, 2009

Kaposi sarcoma (KS) has more recently beenclassified by the World Health Organization as aborderline to low-grade malignant vascular tumor.1,2

The reclassification from the initial malignantneoplasm is based on its reduced biologic potential formetastasis.2 The histologic appearance of cutaneousKS does not vary significantly between clinicalsubtypes as it classically progresses from patch toplaque and finally nodular stages.3,4 Where fourclinical subtypes are usually recognized, in recentdecades, there has been an increasing awareness ofa wider histologic spectrum, which has resulted ina growing number of reported histologic variantsof KS, including lymphangioma-like, telangiectatic,anaplastic, micronodular, intravascular, ecchymotic,keloidal, hyperkeratotic types.4– 6 Rare case reportson the anaplastic and lymphangioma-like variantsof KS indicate that they may be associated withan aggressive clinical course; signifying the need to

recognize these variants as failure to identify may leadto delayed diagnosis, management and increasingmorbidity.7– 10

We present a case of anaplastic Kaposi’s sarcomawith definitive involvement of the skin and lymphnodes. Unique features included the histologicphenotype and aggressive clinical course.

Case reportA 53-year-old African American male with humanimmunodeficiency virus (HIV) infection, an acquiredimmune deficiency syndrome (AIDS)-defining illnessof unknown duration and a most recent CD4 count of122 was admitted for fever, chills, productive coughand respiratory distress. He was started on highlyactive antiretroviral therapy (HAART) 1 month priorto admission. On admission, patient was noted tohave multiple 0.3–0.7 cm, red to violaceous maculesand papules, located on the face, chest (Fig 1A,B),

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(A) (B)

Fig. 1. Multiple, round to oval, red to violaceous macules and papules on the A) chest and B) forehead.

abdomen and back in addition to multiple swollen(>1.5 cm) lymph nodes in the inguinal, cervical andaxilla region. No lesions were noted in the oral mucosaor on the palms or soles. Clinical impression was thatof KS and a punch biopsy of lesions from the leftchest and forehead were performed which revealedsimilar histologic features. These included a haphaz-ard proliferation of predominantly epithelioid cellsexhibiting moderate cellular pleomorphism, markedcytologic atypia, mitoses and a stromal component ofextravasated erythrocytes with admixed plasma cells.The epithelioid cytomorphology and the absence of afrankly fascicular spindled cell component obscuredthe vasoformative nature of the tumor for which

reason immunohistochemical stains were performed.Immunohistochemical stain CD31 confirmed the vas-cular nature of the proliferation and a diagnosis ofanaplastic Kaposi’s sarcoma was rendered. Addi-tional immunohistochemical stain HHV-8 revealingdiffuse positive nuclear staining in majority of thelesional cells further confirmed the histologic diagno-sis (Fig. 2A–D).

Given the patient’s worsening lymphadenopathyand pulmonary symptoms, a biopsy of the cervicallymph node was performed, which also revealedinvolvement by KS, confirmed by immunohisto-chemical stain HHV-8 (Fig. 3A,B). Additional clinicalworkup included a bronchoscopy, revealing granular

(A) (B)

(C) (D)

Fig. 2. Punch biopsy of lesion from the left chest: A) H&E, low power; B) H&E, high power; C) immunohistochemical staining with HHV-8,low power; and D) immunohistochemical staining with HHV-8, low power.

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(A) (B)

Fig. 3. Cervical lymph node biopsy:A) H&E, low power and B) H&E, highpower.

mucosa and plaques, a computerized tomographyscan of the neck, chest, abdomen and pelvis showingdiffuse bilateral cervical lymphadenopathy as well asenlarged nodes in the mediastinum and around therenal hilar. Given this, the patient was presumedto have pulmonary parenchymal KS and staged atT1I1S1. Although he was continued on HAARTtherapy, given the widespread skin, lymph node andsymptomatic lung involvement, he was started onpegylated liposomal doxorubicin. His respiratory sta-tus, however, continued to deteriorate and he expiredwithin 1 week of the initial diagnosis of anaplastic KS.

DiscussionThe recently expanded histologic variants of KSinclude lymphangioma-like KS, telangiectatic KS,anaplastic KS, micronodular KS, intravascular KS,ecchymotic KS, keloidal KS and hyperkeratoticKS.6– 16 An uncommon histologic variant, anaplasticKS, sometimes referred to as pleomorphic KS, isclinically notable for its high local aggressiveness,along with its metastatic capacity. Our case confirmsthe clinically aggressive nature of this rare histologicvariant as our patient deteriorated and expired within1 week after the diagnosis of KS despite on HAARTand systemic chemotherapy agent. All of the fivepatients with anaplastic transformation of classicKS described in the article by Satta et al. wereHIV negative and older in age (ranging from 74to 85 years old) when compared with our patientwho was only 53 years old and HIV positive.8However, similar to our case, all five patients showedaggressive clinical course with little response despitechemotherapy.8 Satta et al. hypothesized that therapid progression of anaplastic KS was becauseof an intrinsic genetic instability of the malignantcell resulting in clonal progression of the neoplasticphenotype.8 The younger age of our patient raises theother possibility, albeit one that is speculative for now,that immune suppression secondary to HIV infectionmay actually act as a predisposing factor for anaplastictransformation in younger patients. Questioning thecontributory role of immunosuppression to rapid

clinical progression of anaplastic KS, however, is thereport by Salameire et al. of a patient who presentedwith anaplastic KS mimicking a Stewart–Trevessyndrome but responded well to the chemotherapy.17

While this patient lacked evidence of metastaticKS clinically or radiologically, the patient had a10-year history of Wegener’s granulomatosis treatedby cyclosphosphamide.

The paucity of reports of anaplastic KS in theliterature makes it difficult to correlate its preciseclinical features. While some cases appear to presentwith small nodules and papules, similar to ours,others appear to present with exophytic masses andtumors with ulceration.8 The clinical conundrum isparalleled by the histology of these lesions wheremore often than not the vasoformative nature of theneoplasm is not easily discerned and differentiationfrom other malignant tumors often requires acomprehensive panel of immunohistochemical stains.Compounding the issue even further are reportsof HHV-8-associated solid anaplastic lymphomain patients with AIDS-associated KS.18 These aretypically CD30 positive, unlike our case that wasCD30 negative. Based on findings from our caseand those previously reported in the literature,unifying histologic features of anaplastic KS include asolid/nodular proliferation of frankly anaplastic cellsexhibiting cytologic atypia, cellular pleomorphismand mitotic activity. Despite the atypia in the cellularcomponent, the stromal component, like that ofclassic KS and is plasma cell-rich and containsextravasated erythrocytes.

Using the pre-AIDS epidemic (1975–1979) USpopulation as the reference group, persons withAIDS have a risk for KS that is 100,000-foldgreater than that in the general population.19

This markedly increased risk in HIV-infectedindividuals is multifactorial and attributed to a highprevalence of coinfection with HHV-8,20 whichis etiopathologically linked to KS.21 With theintroduction of HAART therapy, a decline in theincidence of Kaposi’s sarcoma associated with HIVinfection was noted.22,23 These reductions have been

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attributed to improved immune function directlyrelating to HAART therapy.22 Patients with Kaposi’ssarcoma typically have a low CD4 cell count (<150cells per cubic millimeter) and a high viral load(>10,000 copies per millilitre).22,24 In the majorityof patients, regression of Kaposi’s sarcoma has beenreported to occur within 8 months after the initiationof antiretroviral therapy, paralleling the increasein the CD4 cell count and decrease in the viralload that mark successful therapy.25 An unusualfeature of our case is that our patient was previoushealthy and had no particular triggering events priorto this admission that he could recall. However,he was diagnosed with HIV/AIDS for unknownduration with a CD4 count less than 150, and noton HAART until 1 month prior to admission. Thisindicates that he may have been predisposed to long-term immunosuppression as a consequence of HIVinfection that this, in turn, may have contributedto the anaplastic transformation and his subsequentaggressive clinical course with multi-organ KSinvolvement and ultimately multi-organ systemfailure despite therapy with HAART, antibiotics,and 1 week course of systemic chemotherapeuticagent.

In conclusion, we report a rare histologic variantof KS with definite involvement of the skin and thelymph nodes in an HIV-infected previously healthymale. Histologic features of this variant include a solidor nodular, haphazard proliferation of predominantlyepithelioid cells exhibiting cellular pleomorphismand cytologic atypia including mitoses and astromal component of extravasated erythrocyteswith admixed plasma cells. Although the epithelioidcytomorphology and the absence of a franklyfascicular spindled cell component often obscure thevasoformative nature of the tumor, recognition ofthis uncommon variant is important as it signifies anaggressive clinical course and poor prognosis despiteaggressive therapy. This is of particular clinicalsignificance in a younger patient with KS as it suggestsadditional screening for cause of immunosuppressionincluding HIV infection.

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