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Histological variants of cutaneous Kaposi sarcoma
© Grayson and Pantanowitz; licensee BioMed Central Ltd. 2008
Received: 23 July 2008
Accepted: 25 July 2008
Published: 25 July 2008
This review provides a comprehensive overview of the broad clinicopathologic spectrum of cutaneous Kaposi sarcoma (KS) lesions. Variants discussed include: usual KS lesions associated with disease progression (i.e. patch, plaque and nodular stage); morphologic subtypes alluded to in the older literature such as anaplastic and telangiectatic KS, as well as several lymphedematous variants; and numerous recently described variants including hyperkeratotic, keloidal, micronodular, pyogenic granuloma-like, ecchymotic, and intravascular KS. Involuting lesions as a result of treatment related regression are also presented.
Kaposi sarcoma (KS) is a vascular lesion of low-grade malignant potential that presents most frequently with skin lesions. Most histopathologists are au fait with the histologic picture of usual (typical) cutaneous KS as it progresses from patch, to plaque and finally nodular stages [1–4]. This morphologic spectrum of "usual" KS is common to classic, African endemic, transplant-associated, and acquired immune deficiency syndrome (AIDS)-associated KS . In recent decades, however, there has been an increasing awareness of a wider histologic spectrum [5, 6]. This has resulted in a growing number of reported clinical and/or histologic variants of KS. Failure to identify a given lesion as KS could lead to delayed diagnosis or inappropriate management. It has also been suggested that certain variants, such as anaplastic KS and possibly lymphangioma-like KS, might have prognostic relevance [7–9].
Taking these factors into account, we have elected to divide KS skin lesions into four broad groups: (1) KS lesions which encompass usual variants related to disease progression, (2) KS variants alluded to in the older literature, (3) more recently described KS variants, and (4) KS lesions as a consequence of therapy. Although the apparent histogenesis of some of these morphologic variants is known, the pathogenesis of others is uncertain or subject to speculation. Hyperkeratotic KS, by way of example, frequently occurs as a result of KS-associated chronic lymphedema of the lower extremities . Intravascular KS, on the other hand, could either originate primarily as an intravascular proliferation, or alternatively develop as a consequence of intravascular extension of a lesion breaching the vessel wall . KS lesions arising in extracutaneous locations often differ histologically from their counterparts in the skin, including the recent description of "in situ" KS involving mediastinal lymphatic vessels .
Usual variants related to progression
Large cutaneous nodules may frequently undergo ulceration. Superficial shave biopsies of such lesions may be diagnostically challenging to the histopathologist, as most of the specimen may contain only an inflammatory exudate with underlying granulation tissue; this may be misinterpreted as a pyogenic granuloma . Distinguishing between spindle cells from granulation tissue and lesional KS cells from the uppermost portion of an underlying KS nodule can be difficult, if not impossible without the aid of immunohistochemistry. The commercial antibody to HHV-8 LNA-1 and the lymphatic endothelial cell marker D2-40 may prove very useful in this context. Staining with these markers is preferable to less specific vascular markers such as CD31 or CD34, as these do not facilitate recognition of the lesional and non-lesional endothelial cell populations. Rare instances of acquired immune deficiency syndrome (AIDS)-associated KS harboring a concomitant opportunistic pathogen (e.g. cryptococcosis) may also go undiagnosed in superficial biopsy material [14, 15]. Superficial shave biopsies, therefore, should be discouraged.
Lesions that may potentially be confused histologically with nodular KS include bacillary angiomatosis, other vascular tumors (e.g. spindle cell hemangioma and Kaposiform hemangioendothelioma), fibrohistiocytic tumors (e.g. cellular, angiomatoid and atypical variants of fibrous histiocytoma, and dermatofibrosarcoma protuberans), resolving dermal fasciitis, spindle cell melanoma, and several other spindle cell mesenchymal neoplasms (e.g. cutaneous leiomyosarcoma) [1, 2, 4].
Variants reported in the older literature
Anaplastic Kaposi sarcoma
Anaplastic KS, sometimes referred to as pleomorphic KS, is poorly documented in the literature, possibly because of its rarity. Malignant transformation of KS, characterized by an increase in the number of mitoses and marked cellular pleomorphism, was first described in 1959 by Cox and Helwig . A "monomorphic" variant was identified by Templeton in several cases of African KS . In a review of KS cases from Uganda (in 1971), investigators distinguished KS with a "monocellular pattern" (resembling anaplastic KS) from a so-called "anaplastic variant pattern" (resembling angiosarcoma) . Anaplastic histology has been described in the context of classic, African, and AIDS-associated KS [7, 8, 19–24]. We are unaware of a report of this rare variant following iatrogenic immunosuppression.
It is easy to appreciate why a host of other malignant spindle cell neoplasms might be entertained in the histologic differential diagnosis, including certain sarcomas (e.g. leiomyosarcoma, spindle cell rhabdomyosarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma), amelanotic spindle cell melanoma, and spindle cell carcinoma [14, 15, 20]. Angiosarcoma might also be considered, particularly if erythrocytes are identified between the markedly atypical spindled cells. A comprehensive panel of immunohistochemical stains is often required to rule out the aforementioned entities and confirm the presence of KS . It is plausible that a proportion of anaplastic KS cases reported in the earlier literature, prior to the advent of immunohistochemistry, might not have been true cases of KS after all.
There are several variants of lymphedematous KS, all of which can present clinically with a deceptive bulla-like appearance (Figures pending permission). The interchangeable terminology that has been used in the literature for these variants is confusing. An attempt to classify this issue has been made , and includes variants associated with ectatic lymphatics such as lymphangioma-like and lymphangiectactic KS, and/or due to the accumulation of superficial dermal edema such as the subepidermal and intraepidermal (lymphatic) bullous KS variants. Most of these variants usually contain an admixture of more stereotypical KS lesions. In those cases where these lymphedematous variants form the predominant or sole histological pattern, the diagnosis of KS may be problematic.
Lymphangioma-like KS (LLKS), also referred to as "lympangiomatous" KS, is an uncommon variant that may be encountered in all four major clinicopathologic groups of KS patients [27–33]. Furthermore, lymphangioma-like morphology can occur in patch, plaque or nodular stage lesions . This variant is said to account for less than 5% of KS cases . Although Ronchese and Kern in 1957 are often credited with first describing the condition, the first reported case actually appears to date back to 1923, noted in a 66-year-old woman with clinical bullous KS lesions, the histology of which was described as being analogous to lymphangioma circumscriptum [27, 34]. LLKS is most likely related to lymphedematous KS, bullous KS and hyperkeratotic (or verrucous) KS, as many of the reported patients with these clinical variants of KS have shown histopathologic features of LLKS on skin biopsy [10, 26, 27, 34–39]. In some case reports patients with LLKS manifested with widespread and pronounced lymphedema  as well as effusions .
Lymphangiectatic Kaposi sarcoma
Bullous Kaposi sarcoma
Hyperkeratotic (Verrucous) Kaposi sarcoma
Keloidal Kaposi sarcoma
Pyogenic granuloma-like Kaposi sarcoma
Ecchymotic Kaposi sarcoma
Intravascular Kaposi sarcoma
The only description of intravascular KS is limited to a report of six cases, including four patients with classic KS and two with AIDS-associated KS . Histologic examination in this small series showed an exclusively intravascular solid spindle cell KS proliferation. Immunohistochemical stains for desmin and smooth muscle actin (SMA) confirmed that this proliferation was indeed intravenous. The histologic differential diagnosis includes intravascular papillary endothelial hyperplasia, intravenous PG, intravascular fasciitis, papillary intralymphatic angioendothelioma (Dabska tumor) and intravascular myopericytoma .
Variants related to therapy
Therapy may result in KS regression, and less likely exacerbation (so-called KS flare) . The histopathology of regression in KS has been previously described and is discussed below. KS exacerbation (flare or recrudescence) can occur following therapy with corticosteroids, after treatment with rituximab, or as part of the immune reconstitution inflammatory syndrome (IRIS) seen with antiretroviral therapy in HIV-infected persons . The histomorphology of KS flare lesions has yet to be described.
Regressing Kaposi sarcoma
KS clearly has the ability to develop into lesions of varying morphologic appearance. It is important to be able recognize these variants in order to avoid potential misdiagnosis and improper management of afflicted patients. KS has been shown to be of lymphatic origin . This may explain the intimate association of abnormal lymphatics observed in several of these variants, such as lymphangioma-like and lymphangiectatic KS. KS is also intimately associated with lymphedema. Chronic lymphedema may even precede KS lesions. Some authors believe that chronic lymphedema may promote KS development due to a combination of collateral vessel formation, lympahngiogenesis and immune impairment . Hyperkeratotic and bullous KS variants can be attributed to the long standing effects of tumor-associated lymphedema on the overlying epidermis. Deep dermal fibroma-like nodules seen in cases associated with marked lymphedema could explain the origin of micronodular KS. The clinical significance of most of these KS variants has not been studied. Lymphedematous variants have been postulated to portend a poor prognosis. This is certainly plausible given the fact that significant KS-related edema carries a grave prognosis . Anaplastic KS is perhaps the only variant associated with aggressive behaviour. The reason for progressive histological dedifferentiation in some cases of KS is unknown. Studies looking at the role of HHV-8 and the host (e.g. immunity) in anaplastic cases may provide some answers.
- Ackerman AB: Histologic features of Kaposi's sarcoma and simulators of it. Kaposi's sarcoma. Edited by: Cerimele D. 1985, Spectrum Publications, Inc., New York, 71-79.Google Scholar
- Templeton AC: Pathology. Kaposi's sarcoma: Pathophysiology and clinical management. Edited by: Ziegler JL, Dorfman RF. 1988, Marcel Dekker, Inc., New York, 23-70.Google Scholar
- Ackerman AB, Gottlieb GJ: Atlas of the gross and microscopic features. Kaposi's sarcoma: A text and atlas. Edited by: Gottlieb GJ, Ackerman AB. 1988, Lea & Febiger, Philadelphia, 29-72.Google Scholar
- Sangüeza OP, Requena L: Malignant neoplasms. Kaposi's sarcoma. Pathology of vascular skin lesions. Clinicopathologic correlations. Edited by: Sangüeza OP, Requena L. 2003, Humana Press, New Jersey, 217-235.View ArticleGoogle Scholar
- Schwartz RA: Kaposi's sarcoma: an update. J Surg Oncol. 2004, 87: 146-151.View ArticlePubMedGoogle Scholar
- Jessop S: HIV-associated Kaposi's sarcoma. Dermatol Clin. 2006, 509-520.Google Scholar
- Cerimele D, Carlesimo F, Fadda G, Rotoli M, Cavalieri S: Anaplastic progression of classic Kaposi's sarcoma. Dermatology. 1997, 194: 287-289.View ArticlePubMedGoogle Scholar
- Rwomushana RJ, Bailey IC, Kyalwazi SK: Kaposi's sarcoma of the brain. A case report with necropsy findings. Cancer. 1975, 36: 1127-1131.View ArticlePubMedGoogle Scholar
- Liebowitz MR, Dagliotti M, Smith E, Murray JF: Rapidly fatal lymphangioma-like Kaposi's sarcoma. Histopathology. 1975, 4 (5): 559-566.View ArticleGoogle Scholar
- Hengge UR, Stocks K, Goos M: Acquired immune deficiency syndrome-related hyperkeratotic Kaposi's sarcoma with severe lymphoedema: report of five cases. Br J Dermatol. 2000, 142: 501-505.View ArticlePubMedGoogle Scholar
- Luzar B, Antony F, Ramdial PK, Calonje E: Intravascular Kaposi's sarcoma – a hitherto unrecognised phenomenon. J Cuta Pathol. 2007, 34 (11): 861-864.View ArticleGoogle Scholar
- Konstantinopoulos PA, Dezube BJ, Pantanowitz L: Morphologic and immunophenotypic evidence of in-situ Kaposi's sarcoma. BMC Clin Pathol. 2006, 6: 7-PubMed CentralView ArticlePubMedGoogle Scholar
- Ackerman AB: Subtle clues to diagnosis by light microscopy. The patch stage of Kaposi's sarcoma. Am J Dermatopathol. 1979, 1: 165-172.View ArticlePubMedGoogle Scholar
- Grayson W: A re-appraisal of vascular proliferations in human immunodeficiency virus infected patients. S Afr Dermatol Rev. 2006, 6: 48-57.Google Scholar
- Grayson W: My approach to: The HIV-positive skin biopsy. J Clin Pathol. 2008, 61: 802-817.View ArticlePubMedGoogle Scholar
- Cox FH, Helwig EB: Kaposi's sarcoma. Cancer. 1959, 12: 289-298.View ArticlePubMedGoogle Scholar
- Templeton AC: Kaposi's sarcoma. Pathol Annu. 1981, 16: 315-336.PubMedGoogle Scholar
- Taylor JF, Templeton AC, Vogel CL, Ziegler JL, Kyalwazi SK: Kaposi's sarcoma in Uganda: a clinico-pathological study. Int J Cancer. 1971, 8: 122-135.View ArticlePubMedGoogle Scholar
- O'Connell KM: Kaposi's sarcoma: histopathological study of 159 cases from Malawi. J Clin Pathol. 1977, 30: 687-695.PubMed CentralView ArticlePubMedGoogle Scholar
- Owor R: Conventional Kaposi's sarcoma in Africa. Kaposi's sarcoma: A text and atlas. Edited by: Gottlieb GJ, Ackerman AB. 1988, Lea & Febiger, Philadelphia, 143-149.Google Scholar
- Ngendahayo P, Mets T, Bugingo G, Parkin DM: Kaposi's sarcoma in Rwanda: clinico-pathological and epidemiological aspects. Bull Cancer. 1989, 76: 383-394.PubMedGoogle Scholar
- Satta R, Cossu S, Massarelli G, Cottoni F: Anaplastic transformation of classic Kaposi's sarcoma: clinicopathological study of five cases. Br J Dermatol. 2001, 145: 847-849.View ArticlePubMedGoogle Scholar
- Nayler SJ, Goetsch S, Grayson W, Taylor L: Pleomorphic Kaposi's sarcoma: Characterisation of an under-recognised variant of Kaposi's sarcoma. Mod Pathol. 2000, 13: 13A-View ArticleGoogle Scholar
- Craddock KJ, Labonte S, Ghazarian D: Anaplastic Kaposi sarcoma resembling epithelioid angiosarcoma in an HIV-positive man. Eur J Dermatol. 2008, 18: 358-359.PubMedGoogle Scholar
- Weiss SW, Goldblum JR: Enzinger and Weiss's soft tissue tumors. 2008, Mosby, Philadelphia, 721-732. 5Google Scholar
- Pantanowitz L, Duke WH: Lymphoedematous variants of Kaposi's sarcoma. J Eur Acad Dermatol Venereol. 2008, 22: 118-120.PubMedGoogle Scholar
- Ronchese F, Kern AB: Lymphangioma-like tumors in Kaposi's sarcoma. AMA Arch Derm. 1957, 75: 418-427.View ArticlePubMedGoogle Scholar
- Gange RW, Jones EW: Lymphangioma-like variant of Kaposi's sarcoma. A report of three cases. Br J Dermatol. 1979, 100: 327-334.View ArticlePubMedGoogle Scholar
- Cossu S, Satta R, Cottoni F, Massarelli G: Lymphangioma-like variant of Kaposi's sarcoma: clinicopathologic study of seven cases with review of the literature. Am J Dermatopathol. 1997, 19: 16-22.View ArticlePubMedGoogle Scholar
- Davis DA, Scott DM: Lymphangioma-like Kaposi sarcoma: Etiology and literature review. J Am Acad Dermatol. 2000, 43: 123-127.View ArticlePubMedGoogle Scholar
- Ramirez JA, Laskin WB, Guirart J: Lymphangioma-like Kaposi sarcoma. J Cutan Pathol. 2005, 32: 286-292.View ArticlePubMedGoogle Scholar
- Mohanna S, Sanjez J, Ferrufino JC, Bravo F, Gotuzzo E: Lymphangioma-like Kaposi's sarcoma: report of four cases and review. J Eur Acad Dermatol Venereol. 2006, 20: 999-1032.Google Scholar
- Kalambokis G, Kitsanou M, Stergiopoulou C, Zioga A, Dimou S, Tsianos EV: Lymphangioma-like Kaposi's sarcoma with gastric involvement in a patient with lung cancer. J Eur Acad Dermatol Venereol. 2005, 19: 653-654.View ArticlePubMedGoogle Scholar
- Borroni G, Brazzelli V, Vignoli GP, Gaviglio MR: Bullous lesions of Kaposi's sarcoma: case report. Am J Dermatol. 1997, 19: 379-383.View ArticleGoogle Scholar
- Allen JA, Gillespie DL, Redfield RR, Gomez ER: Lower extremity lymphedema caused by acquired immune deficiency syndrome-related Kaposi's sarcoma: case report and review of the literature. J Vasc Surg. 1995, 22: 178-181.View ArticlePubMedGoogle Scholar
- Recht B, Nickoloff BJ, Wood GS: A bullous variant of Kaposi's sarcoma in an elderly female. J Dermatol Surg Oncol. 1986, 12: 1192-1197.View ArticlePubMedGoogle Scholar
- Ruocco V, Astarita C, Guerra V, Lo Schiavo A, Moscariello CG, Satriano RA: Kaposi's sarcoma on a lymphedematous immunocompromised limb. Int. J Dermatol. 1984, 23: 56-60.Google Scholar
- Atillasoy ES, Santoro A, Weinberg JM: Lymphedema associated with Kaposi's sarcoma. J Eur Acad Dermatol. 2001, 15: 364-365.Google Scholar
- Ramdial PK, Chetty R, Singh B, Singh R, Aboobaker J: Lymphedematous HIV-associated Kaposi's sarcoma. J Cutan Pathol. 2006, 33: 474-481.View ArticlePubMedGoogle Scholar
- Bossuyt L, Oord Van den JJ, Degreef H: Lymphangioma-like variant of AIDS-associated Kaposi's sarcoma with pronounced edema formation. Dermatology. 1995, 190: 324-326.View ArticlePubMedGoogle Scholar
- Miller RM, Leibowitz MR: The radiological features of lymphangioma-like Kaposi's sarcoma. A case report. S Afr Med J. 1979, 56: 146-148.PubMedGoogle Scholar
- Guillou L, Fletcher CD: Benign lymphangioendothelioma (acquired progressive lymphangioma): a lesion not to be confused with well-differentiated angiosarcoma and patch stage Kaposi's sarcoma: clinicopathologic analysis of a series. Am J Surg Pathol. 2000, 24: 1047-1057.View ArticlePubMedGoogle Scholar
- Snyder RA, Schwartz RA: Telangiectatic Kaposi's sarcoma. Occurrence in a patient with thymoma and myasthenia gravis receiving long-term immunosuppressive therapy. Arch Dermatol. 1982, 118: 1020-1021.View ArticlePubMedGoogle Scholar
- Caputo R, Gianotti R, Grimalt R, Monti M, Alessi E: Soft fibroma-like lesions on the legs of a patient with Kaposi's sarcoma and lymphedema. Am J Dermatopathol. 1991, 13: 493-496.View ArticlePubMedGoogle Scholar
- Sathyakumar S, Suh JS, Sharp VL, Polsky B: Images in HIV/AIDS. Elephantiasis nostras verrucosa secondary to Kaposi sarcoma: a rare case. AIDS Read. 2008, 18: 81-82.PubMedGoogle Scholar
- Schwartz RA, Spicer MS, Janninger CK, Cohen PJ, Melczer MM, Lambert WC: Keloidal Kaposi's sarcoma: Report of three patients. Dermatology. 1994, 189: 271-274.View ArticlePubMedGoogle Scholar
- Kempf W, Cathomas G, Burg G, Trueb RM: Micronodular Kaposi's sarcoma – A new variant of classic-sporadic Kaposi's sarcoma. Dermatology. 2004, 208: 255-258.View ArticlePubMedGoogle Scholar
- Urquhart JL, Uzieblo A, Kohler S: Detection of HHV-8 in pyogenic granuloma-like Kaposi sarcoma. Am J Dermatopathol. 2006, 28: 317-321.View ArticlePubMedGoogle Scholar
- Schwartz RA, Spicer MS, Thomas I, Janninger CK, Lambert WC: Ecchymotic Kaposi's sarcoma. Cutis. 1995, 56: 104-106.PubMedGoogle Scholar
- Bassioukas K, Zioga A, Hantschke M, Klouvas G, Hatzis J: Hemorrhagic Kaposi sarcoma. Successful treatment with IFN-alpha. Eur J Dermatol. 2004, 14: 37-40.PubMedGoogle Scholar
- Pantanowitz L, Duke WH: Intravascular lesions of the hand. Diagn Pathol. 2008, 3: 24-PubMed CentralView ArticlePubMedGoogle Scholar
- Pantanowitz L, Dezube BJ: Kaposi's sarcoma: progression, exacerbation and regression. Cancer Research Journal. 2008,Google Scholar
- Parra R, Leal M, Delgado J, Macias J, Rubio A, Gomez F, Soriano V, Sanchez-Quijano A, Pineda JA, Lissen E: Regression of invasive AIDS-related Kaposi's sarcoma following antiretroviral therapy. Clin Infect Dis. 1998, 26: 218-219.View ArticlePubMedGoogle Scholar
- Wit FW, Sol CJ, Renwick N, Roos MT, Pals ST, van Leeuwen R, Goudsmit J, Reiss P: Regression of AIDS-related Kaposi's sarcoma associated with clearance of human herpesvirus-8 from peripheral blood mononuclear cells following initiation of antiretroviral therapy. AIDS. 1998, 12: 218-219.PubMedGoogle Scholar
- Eng W, Cockerell CJ: Histological features of kaposi sarcoma in a patient receiving highly active antiviral therapy. Am J Dermatopathol. 2004, 26: 127-32.View ArticlePubMedGoogle Scholar
- Pantanowitz L, Dezube BJ, Pinkus GS, Tahan SR: Histological characterization of regression is acquired immunodeficiency syndrome-related Kaposi's sarcoma. J Cutan Pathol. 2004, 31: 26-34.View ArticlePubMedGoogle Scholar
- Pantanowitz L, Dezube BJ, Hernandez-Barrantes S, Tahan SR, Dabbous MK: Matrix metalloproteinases in the progression and regression of Kaposi's sarcoma. J Cutan Pathol. 2006, 33: 793-8.View ArticlePubMedGoogle Scholar
- Cheung L, Rockson SG: The lymphatic biology of Kaposi's sarcoma. Lymphat Res Biol. 2005, 3: 25-35.View ArticlePubMedGoogle Scholar
- Ruocco V, Schwartz RA, Ruocco E: Lymphedema: an immunologically vulnerable site for development of neoplasms. J Am Acad Dermatol. 2002, 47: 124-127.View ArticlePubMedGoogle Scholar
- Feller L, Masipa J, Wood N, Raubenheimer E, Lemmer J: The prognostic significance of facial lymphoedema in HIV-seropositive subjects with Kaposi sarcoma. AIDS Res Ther. 2008, 5: 2-PubMed CentralView ArticlePubMedGoogle Scholar
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