Dermatologic Manifestations of Kaposi Sarcoma Workup
- Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD more...
Serum glucose levels may reflect an increased incidence of diabetes mellitus in patients with classic Kaposi sarcoma (KS). Ketoacidosis is unusual in these patients.
Immunohistochemical detection of human herpes virus-8 latent nuclear antigen-1 has been claimed as useful in the diagnosis of Kaposi sarcoma.
Hemogram in nonimmunosuppressed patients with Kaposi sarcoma tends to be within normal limits, but occasionally, monocytosis or eosinophilia has been noted. Eosinophilia is seen especially in African patients and patients who are homosexual, in whom parasitosis may be common.
In KS-AIDS, cytopenia of 1 or more cell lines is frequent.
Anemia, if present, may result from gastrointestinal bleeding or may be associated with an autoimmune hemolytic anemia or a hematologic malignancy.
Assays for HHV-8 have been challenging. At present, no universally accepted method exists.
Polymerase chain reaction often is used but may have false-positive results because of its high susceptibility to contamination.
Methods based on both lytic and latent-phase viral antigens remain promising.
Computed tomography (CT) may be valuable, especially abdominal CT scans in patients with AIDS. In AIDS-related Kaposi sarcoma, early lymphatic and hepatosplenic involvement may be evident. Consider CT-directed fine needle aspiration to provide tissue confirmation, since lymphomas and atypical mycobacterial and other infections may appear similar.
Consider endoscopic and conventional radiographic studies; however, these modalities may miss gastrointestinal Kaposi sarcoma, while selective angiography may demonstrate Kaposi sarcoma.
Radionucleotide scans may be useful in demonstrating visceral Kaposi sarcoma and associated lymphoma.
With lung nodules, the distinction between Kaposi sarcoma, lymphoma, and/or opportunistic infection may be challenging.
In both adults and children with pulmonary Kaposi sarcoma, chest radiography shows perihilar and lower zone involvement. Pleural effusions appear to be more common on radiographs in children.
Evaluation for Kaposi sarcoma should include a complete physical examination and a biopsy of suspected lesions including lymph nodes. CT scan used to guide a fine needle for tissue specimens appears promising.
The cell of origin in Kaposi sarcoma remains a subject of dispute, although the following tests may be useful:
Ultrastructural and immunohistochemical testing favor the endothelial cell.
The presence of factor VIII–related antigen, human leukocyte antigen DR (HLA-DR), von Willebrand factor, and the lectin Ulex europaeus I (which all are markers for endothelial cells) is highly suggestive.
Reactivity with 2 monoclonal antibodies (EN4 and PAL E) implies that Kaposi sarcoma is derived from endothelium of lymphatic origin; however, Kaposi sarcoma spindle cells express CD34 antigen, a glycoprotein expressed by endothelial cells of small blood vessels (but not those of lymphatic origin).
Kaposi sarcoma (KS) tends to demonstrate increased spindle cells with vascular slits and vascular structures with a predominance of endothelial cells. Extravasated erythrocytes and hemosiderin-laden macrophages often are evident. Some spindle cells may show nuclear pleomorphism. Early Kaposi sarcoma may resemble granulation tissue with a diffuse chronic inflammatory infiltrate and capillaries dilated and increased in number. This pattern also is seen in lymph nodes and viscera.
Histopathologic classification is based on relative contribution of spindle cells, fibrosis, and nuclear pleomorphism, sometimes divided into 3 histopathologic forms, which include (1) a mixed form with an equal amount of spindle cells, vascular clefts, and capillaries, (2) a mononuclear type with 1 cell type predominating, and (3) an anaplastic form with cellular pleomorphism and numerous mitotic figures. In 2007, intravascular Kaposi sarcoma was recognized as a morphological variant of Kaposi sarcoma that seems to be unassociated with an increased risk of aggressive behavior.
Cutaneous Kaposi sarcoma probably evolves through the early inflammatory or patch stage, progresses to the nodular stage, and then, to the late proliferative or plaque stage. The authors believe that the glomeruluslike vascular formations in early patch stage Kaposi sarcoma and in some later lesions may reflect the histogenesis of Kaposi sarcoma. The late plaque stage shows diffuse involvement of the dermis, exhibiting the histologic features of the nodular stage. The lesions may resolve, with involution of the vascular components and formation of scar tissue, or, occasionally, they become extremely pleomorphic and invade deeper tissues. Histologic variants have been recently emphasized. The angiomatous variant demonstrates neoplastic vessel staining with podoplanin, which is not noted with preexisting vessels.
Kaposi sarcoma specimens may be stained for iron and HHV-8. Iron staining of dermal tissue may suggest Kaposi sarcoma. Immunohistochemical stains for HHV-8 should be positive in most typical Kaposi sarcoma. Iron staining and immunohistochemical HHV-8 staining in combination may be reliable markers for Kaposi sarcoma compared with interstitial granuloma annulare.
The lymphadenopathy in Kaposi sarcoma may show marked follicular hyperplasia and hypervascularity, nonspecific inflammation in regional lymph nodes that drain ulcerated Kaposi sarcoma, and lymphomas or actual lymph node Kaposi sarcoma, with or without cutaneous involvement. More than 1 of these processes may be evident in the same node. The authors view localized lymphadenopathic Kaposi sarcoma as a type of localized nodular Kaposi sarcoma. Kaposi sarcoma in nodes shows the typical proliferation of spindle cells separated by slitlike spaces containing red blood cells and is accompanied by marked follicular hyperplasia and plasmacytic infiltration. The earliest changes occur in the subcapsular and trabecular sinuses, with extension into the entire node and, later, the perinodal tissues. Kaposi sarcoma of lymph nodes may be localized or generalized. The lymphocytic, plasmacytic, and immunoblastic proliferation may simulate a lymphoma.
The electron microscopy and immunohistochemical features of Kaposi sarcoma may be important. Staining with CD34, factor VIII–related antigen, the lectin Ulex europaeus I, and HLA-DR antigen may be useful to support or confirm the diagnosis of Kaposi sarcoma. The authors prefer CD34 antigen, which is expressed by Kaposi sarcoma cells, and find it helpful in distinguishing Kaposi sarcoma from pseudo-Kaposi sarcoma (acroangiodermatitis).
See the images below.
Oral Kaposi sarcoma biopsy specimens from 135 cases were placed into 1 of 7 categories based on the predominant pattern of growth : solid, lymphangiomalike, telangiectatic, desmoplastic, lymphangiectatic, ecchymotic, and anaplastic. Some had coexistent pathology, mainly superimposed candidiasis, but also a few had cytomegalovirus and nonnecrotizing granulomatous inflammation. With oral Kaposi sarcoma, some believe that HHV-8 immunohistochemistry is strongly advisable to confirm the diagnosis, although obtaining this immunohistochemistry study may be a challenge in resource-poor countries.
Stage the patient's disease and note any extracutaneous involvement. Staging this multicentric disorder has been a challenge.
The AIDS Clinical Trials Group classification by Krown et al in 1989 uses the following 3 categories, although the tumor/immune/system/systemic (TIS) illness grading method has limitations:
Tumor (T) - Good or bad risk signs (good when Kaposi sarcoma is confined to skin and/or lymph nodes and/or demonstrates minimal oral disease)
Immune system (I) - CD4 cell levels equal to or greater than 150/µL (good risk) versus less than 150/µL (poor risk)
Systemic illness (S) - Good or poor risk
Another classification formula developed by Mitsuyasu in 1987 divides Kaposi sarcoma into the following 4 stages:
Stage I - Localized nodular Kaposi sarcoma in elderly men in North America and Europe
Stage II - Localized, invasive, and aggressive Kaposi sarcoma (mostly seen in Africa)
Stage III - Disseminated mucocutaneous Kaposi sarcoma in African children and patients who are homosexual
Stage IV - Stage III with visceral involvement
In 1984, the authors originally proposed and currently prefer the following classification system (including new recommended modifications):
Stage I represents localized nodular Kaposi sarcoma, with more than 15 cutaneous lesions or involvement restricted to 1 bilateral anatomic site, and few, if any, gut nodules.
Stage II includes both exophytic destructive lesions and locally infiltrative cutaneous lesions as locally aggressive Kaposi sarcoma.
Stage III (generalized lymphadenopathic Kaposi sarcoma) has widespread lymph node involvement, with or without skin lesions, but with no visceral involvement.
Stage IV (disseminated visceral Kaposi sarcoma) has widespread Kaposi sarcoma, usually progressing from Stage II or Stage III, with involvement of multiple visceral organs.
The authors modify each stage as follows:
A: Associated opportunistic infection(s) is evident.
B: Patient is HIV-I seropositive.
C: Cutaneous anergy or other evidence of severe immunodeficiency is present.
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