Cutaneous lymphomas are clonal proliferations of neoplastic T or B cells, rarely natural killer cells or plasmacytoid dendritic cells. Cutaneous lymphomas are the second most common group of extranodal lymphomas. The annual incidence is estimated to be 1 per 100,000.
For rare conditions not dealt with in this Atlas, the reader is referred to Beyer M, Sterry W. Cutaneous lymphoma. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, eds. Fitzpatrick’s Dermatology in General Medicine. 8th ed. New York, NY: McGraw-Hill; 2012:1745-1782.
Adult T Cell Leukemia/Lymphoma
ICD-9: 204.0/208.9 ICD-10: C83/E88
Adult T cell leukemia/lymphoma (ATLL) is a neoplasm of CD4+/CD25+ T cells, caused by human T cell lymphotrophic virus I (HTLV-I).
Manifested by skin infiltrates, hypercalcemia, visceral involvement, lytic bone lesions, and abnormal lymphocytes on peripheral smears.
HTLV-I is a human retrovirus. Infection by the virus does not usually cause disease, which suggests that other environmental factors are involved. Immortalization of some infected CD4+ T cells, increased mitotic activity, genetic instability, and impairment of cellular immunity can all occur after infection with HTLV-I. These events may increase the probability of additional genetic changes, which, by chance, may lead to the development of leukemia 20–40 years after infection in some people (<5%). Most of these effects have been attributed to the HTLV-I-encoded protein tax.
ATLL occurs in southwestern Japan (Kyushu), Africa, the Caribbean Islands, and southeastern United States. Transmission is by sexual intercourse, perinatally, or by exposure to blood or blood products (same as HIV).
There are four main categories. In the relatively indolent smoldering and chronic forms, the median survival is >2 years. In the acute and lymphomatous forms, it ranges from only 4 to 6 months.
Symptoms include fever, weight loss, abdominal pain, diarrhea, pleural effusion, ascites, cough, and sputum. Skin lesions occur in 50% of patients with ATLL. Single to multiple small, confluent erythematous, violaceous papules (Fig. 21-1), ±purpura; firm violaceous to brownish nodules (Fig. 21-2); papulosquamous lesions, large plaques, ±ulceration; trunk > face > extremities; generalized erythroderma; poikiloderma; diffuse alopecia. Lymphadenopathy (75%) sparing mediastinal lymph nodes. Hepatomegaly (50%) and splenomegaly (25%).
Figure 21-1. Adult T cell leukemia/lymphoma A generalized eruption of small, confluent violaceous papules with a predilection for the trunk. The patient had fever, weight loss, abdominal pain, massive leukocytosis with “flower cells” in smear, lymphadenopathy, hepatosplenomegaly, and hypercalcemia.
Figure 21-2. Adult T cell leukemia/lymphoma Firm, violaceous to brownish nodules as shown here are another cutaneous manifestation of ATLL. These nodules may ulcerate.
Patients are seropositive (ELISA, Western blot) to HTLV-I; in IV drug users, up to 30% have dual retroviral infection with both HTLV-I and HIV. WBC ranges from normal to 500,000/μL. Peripheral blood smears show polylobulated lymphocytic nuclei (“flower cells”). Dermatopathology reveals lymphomatous infiltrates composed of many large abnormal lymphocytes, ±giant cells, ±Pautrier microabscesses. There is hypercalcemia–in 25% at time of diagnosis of ATLL and in >50% during clinical course; this is thought to be due to osteoclastic bone resorption.
Management consists of various regimens of cytotoxic chemotherapy; the rates of complete response are <30% and responses lack durability, but good results have been obtained with the combination of oral zidovudine and subcutaneous interferon-α in acute and lymphoma-type ATLL patients. Allogeneic hematopoietic stem cell transplantation holds some promise.
Cutaneous T Cell Lymphoma
ICD-9: 202.1/202.2 ICD-10: C84.0/C84.1
Cutaneous T cell lymphoma (CTCL) is a term that applies to T cell lymphoma first manifested in the skin, but since the neoplastic process involves the entire lymphoreticular system, the lymph nodes and internal organs become involved in the course of the disease. CTCL is a malignancy of helper T cells (CD4+).
In the classic form of CTCL, called mycosis fungoides (MF), the malignant cells are cutaneous CD4+ cells, but the clinical entity of MF has now been expanded to the spectrum of CTCL including non-MF CTCLs.
Whereas all MF is CTCL not all CTCLs are MF.
Only the classic MF form is discussed here.
Mycosis Fungoides (MF)
ICD-9: 202.1/202.0 ICD-10: C84.0/C84.1
MF is the most common cutaneous lymphoma.
Arising in mid-to-late adulthood with male predominance of 2:1.
A clonal proliferation of skin-homing CTLA+ CD4+ T cells with an admixture of CD8+ T cells (antitumor response).
Categorized as patch, plaque, or tumor stage.
Related features are pruritus, alopecia, palmoplantar hyperkeratosis, and bacterial infections.
Histologically, epidermotropism of T cells with hyperconvoluted nuclei. In the tumor stage dermal nodular infiltrates.
Prognosis related to stage.
Treatment: symptom-oriented and stage-adapted.
Epidemiology and Etiology
Age of Onset. Median age at diagnosis 55–60 years.
Sex. Male:female ratio 2:1.
Incidence. Uncommon but not rare.
Etiology. Unknown. CTCL is a malignancy of skin-homing CTLA+ CD4+ T cells.
For months to years, often preceded by various diagnoses such as psoriasis, nummular dermatitis, and “large plaque” parapsoriasis. Symptoms: pruritus, often intractable, but may be none.
Skin Findings. Skin lesions are classified into patches, plaques, and tumors. Patients may have simultaneously more than one type of lesions.
Patches. Randomly distributed, scaling or non-scaling patches in different shades of red (Fig. 21-3). Well- or ill-defined; at first superficial, much like eczema or psoriasis (Figs. 21-3 and 21-4) or mimicking dermatophytosis (“mycosis”), and later becoming thicker.
Figure 21-3. Mycosis fungoides In early stages, lesions consist of randomly distributed, well-, and/or ill-defined patches and later plaques as shown here in a 37-year-old male. They may be scaly and appear in various shades of red. They mimic eczema, psoriasis, or dermatophytosis.
Figure 21-4. Mycosis fungoides: patches/plaque stage More advanced stages show confluence of patches and plaques with irregular configuration. This patient had been treated unsuccessfully for psoriasis for 2 years. Morphologically, he could also have extensive, confluent dermatophytosis (see Section 26), but a negative KOH preparation ruled out this diagnosis. Only after a biopsy had been done was the correct diagnosis of MF made.
Plaques. Round, oval, but often also arciform, annular, and of bizarre configuration (Figs. 21-3 and 21-5). Lesions are randomly distributed but in early stages often spare exposed areas.
Figure 21-5. Mycosis fungoides Plaque and early nodular stage with reddish-brownish scaly, and crusted plaques and flat nodules.
Tumors. Later lesions consist of nodules (Figs. 21-5 and 21-6) and tumors, with or without ulceration (Fig. 21-7). Extensive infiltration can cause leonine facies (Fig. 21-8). Confluence may lead to erythroderma (see Section 8). There is palmoplantar keratoderma and there may be hair loss. Poikiloderma may be present from the onset or develop later (Fig. 21-9).
Figure 21-6. Mycosis fungoides: tumor stage Scaly and crusted eczema-like plaques seen on the arm and chest have turned nodular on the shoulder. This patient had similar lesions elsewhere and was staged IIB (T3 N1 M0).
Figure 21-7. Mycosis fungoides: tumors Two large ulcerated tumors on the lower leg of 58-year-old man. These lesions indeed look like mushrooms.
Figure 21-8. Mycosis fungoides: leonine facies In this 50-year-old patient, the disease had started with extremely pruritic, generalized eczema-like plaques on the trunk that had been treated as eczema over a course of 4 years. Massive nodular infiltration of the face occurred only recently leading to a leonine facies.
Figure 21-9. Mycosis fungoides: poikilodermatous lesions (A) Small reticulated, confluent papules mixed with superficial atrophy give the impression of poikiloderma. This patient had patches elsewhere on the body similar to those shown in Fig. 20-3. (B) Poikiloderma in MF can also result from treatment. This patient had been treated with electron beam.
General Examination. Lymphadenopathy, usually after thick plaques and nodules have appeared.
Dermatopathology. Bandlike and patchy infiltrate in upper dermis of atypical lymphocytes (mycosis cells) extending to epidermis and skin appendages. The classic finding is the epidermotropism of this T cell infiltrate, which will form microabscesses in the epidermis (Pautrier microabscesses). In the plaque and tumor stage, the infiltrate extends deep into the dermis and beyond. Mycosis cells are T cells with hyper-chromatic, irregularly shaped (cerebriform) nuclei. Mitoses vary from rare to frequent.
Mycosis cells are activated monoclonal CTLA+ CD4+ T cells. However, lesions of MF often have a CD8+ T cell component, and these cells are considered to reflect an antitumor response.
Hematology. Eosinophilia, 6–12%, can increase to 50%. Buffy coat: abnormal circulating T cells (mycosis cell-type) and increased WBC (20,000/μL). Bone marrow examination is not helpful in early stages.
Chemistry. Lactic dehydrogenase isoenzymes 1, 2, and 3 increased in erythrodermic stage.
Chest X-Ray. Search for hilar lymphadenopathy.
Imaging. In stage I and stage II disease, diagnostic imaging (CT, gallium scintigraphy, liver–spleen scan, and lymphangiography) does not provide more information than biopsies of lymph nodes.
CT Scan. With more advanced disease, to search for retroperitoneal nodes in patients with extensive skin involvement, lymphadenopathy.
Diagnosis and Differential Diagnosis
In the early stages, the diagnosis of MF is a problem. Clinical lesions may be typical, but histologic confirmation may not be possible for years despite repeated biopsies. Immunophenotyping of infiltrating T cells by use of monoclonal antibodies and T cell receptor rearrangement studies. Lymphadenopathy and the detection of abnormal circulating T cells in the blood appear to correlate well with internalorgan involvement.
Differential Diagnosis. Mainly scaling plaques. High index of suspicion is needed in patients with atypical or refractory “psoriasis,” “eczema,” and poikiloderma. MF often mimics psoriasis in being a scaly plaque and disappearing with exposure to sunlight.
Patient Evaluation in MF and Staging. This has to focus on an evaluation of tumor burden, the degree of atypia of malignant cells, and the state of immunocompetence of the patient. Table 21-1 shows a flow sheet of patient evaluation, and Table 21-2 shows the TNM classification and staging of MF.
TABLE 21-1 PATIENT EVALUATION IN MF
TABLE 21-2 TNM STAGING OF MYCOSIS FUNGOIDES
Course and Prognosis
Unpredictable; MF (pre-MF) may be present for years. Course varies with the source of the patients studied. At the NIH, there was a median survival time of 5 years from the time of the histologic diagnosis, while in Europe a less malignant course is seen (survival time, up to 10–15 years). This, however, may be due to patient selection. Prognosis is much worse when (1) tumors are present (mean survival, 2.5 years), (2) there is lymphadenopathy (mean survival, 3 years), (3) >10% of the skin surface is involved with pretumor-stage MF, and (4) there is a generalized erythroderma. Patients <50 years have twice the survival rate of patients >60 years.
Therapy is symptom-oriented and extent of disease- and stage-adapted. In the pre-MF stage, in which the histologic diagnosis is only compatible, but not confirmed, PUVA photochemo-therapy or narrowband UVB treatment is most effective. For histologically proven plaque-stage disease with no lymphadenopathy and no abnormal circulating T cells, PUVA photochemotherapy is also the method of choice, either alone or combined with oral isotretinoin or bexarotene or subcutaneous interferon-α. Also used at this stage are topical chemotherapy with nitrogen mustard in an ointment base (10 mg/dL), topical carmustine (BCNU) (for limited body surface area involvement), and total-body electron-beam therapy, singly or in combination. Isolated tumors are treated with local x-ray or electron-beam therapy. For extensive plaque stage with multiple tumors or in patients with lymphadenopathy or abnormal circulating T cells, electron-beam plus chemotherapy is probably the best combination for now; randomized, controlled studies of various combinations are in progress. Also, extracorporeal PUVA photochemotherapy is being evaluated in patients with Sézary syndrome.
Mycosis Fungoides Variants
Folllculotroplc MF: With preferential involvement of head and neck, with or without mucinosis, degeneration of hair follicles (previously “mucinosis follicularis,” “alopecia mucinosa") (Fig. 21-10).
Figure 21-10. Folliculotropic MF Multiple small follicular papules. This is called “mucinosis follicularis.”
Hypopigmented MF: Hypopigmented patches in patients with dark skin.
Pagetoid reticulosis (Woringer–Kolopp disease) This is a special variant of MF consisting of localized patches and plaques (Fig. 21-11), with a proliferation of neoplastic T cells that expand intraepidermally following a pattern similar to Paget disease. Extracutaneous dissemination has not been observed, and there is an excellent prognosis.
Figure 21-11. Pagetoid reticulosis This singular plaque in the groin of a 53-year-old woman looks like psoriasis with minimal scale. It was asymptomatic and had been present for 10 months. Histopathology revealed intraepidermal T cells in a pagetoid pattern.
Granulomatosus slack skin: Rare subtype of MF with folds of lax skin in the major skin folds (Fig. 21-12).
Figure 21-12. Granulomatous slack skin Firm, platelike infiltrates on the neck and anterior chest and lax skin folds of the axillary and scapular region.
Sézary syndrome: A leukemic variant, see below page 472 and Section 8.
Sézary Syndrome ICD-9: 202.2 ICD-10: L84.1
Sézary syndrome is a rare special variant of MF characterized by universal erythroderma, peripheral lymphadenopathy, and cellular infiltrates of atypical lymphocytes (Sézary cells) in the skin and in the blood.
The disease may arise de novo or, less commonly, result from extension of a preexisting circumscribed MF. It usually occurs in patients >60 years and more commonly in males than in females.
Patients appear sick, shivering, and scared and there is generalized scaling erythroderma with considerable thickening of the skin. Because of the bright red color, the syndrome has been called the “red man syndrome” (see Section 8 and Fig. 8-3). There is diffuse hyperkeratosis of palms and soles, diffuse hair loss that can lead to baldness, and generalized lymphadenopathy.
Dermatopathology: the same as MF. The lymph nodes may contain nonspecific inflammatory cells (dermatopathic lymphadenopathy) or there can be a complete replacement of the nodal pattern by Sézary cells. The cell infiltrates in the viscera are the same as are present in the skin. Immunophenotyping: CD4+ T cells; T cell receptor rearrangement: monoclonal process. There may be a moderate leukocytosis or a normal WBC. The buffy coat contains from 15% to 30% atypical lymphocytes (Sézary cells).
Diagnosis rests on three features: erythroderma, generalized lymphadenopathy, and presence of increased numbers of atypical lymphocytes in the buffy coat.
Note that any exfoliative dermatitis can mimic Sèzary syndrome (see Section 8).
Without treatment, the course is progressive and patients die from opportunistic infections. Management is as in MF, plus appropriate supportive measures required for erythroderma (see Section 8).
Lymphomatoid Papulosis ICD-9: 709.8 ICD-10: L41.2
Lymphomatoid papulosis is an asymptomatic, chronic, self-healing, polymorphous eruption of unknown etiology.
It is a low-grade, self-limited T cell lymphoma with a low but real risk of progression to more malignant forms of lymphoma.
Incidence is 1.2–1.9 cases per million, occurring sporadically in both sexes from childhood to old age; average age 40 years.
Characterized by recurrent crops of lesions that regress spontaneously, with histologic features of lymphocytic atypia.
Pathogenesis unknown; considered to be a low-grade lymphoma perhaps induced by chronic antigenic stimulation and controlled by host mechanisms. It belongs in the spectrum of primary cutaneous CD30+ lymphoproliferative disorders.
Close clinical resemblance to pityriasis lichenoides et varioliformis acuta (see Fig. 3-24). Erythematous to red-brown papules (Fig. 21-13) and nodules, 2–5 mm in diameter, which are initially smooth and hemorrhagic, later hyperkeratotic, with central, black necrosis, crusting (Fig. 21-13), and ulceration. Few to hundreds of lesions, asymptomatic or pruritic, arranged at random and often grouped, recurrent, primarily on trunk and extremities; rarely, oral and genital mucosa. Individual lesions evolve over a 2- to 8-week period and resolve spontaneously. Atrophic hyper- or hypopigmented scarring following ulcerated lesions.
Figure 21-13. Lymphomatoid papulosis Crops of reddish-brown papules appear in waves involving the entire body. Lesions are asymptomatic, become hyperkeratotic, crusted, and necrotic in the center. Since lesions arise asynchronously, all stages in this evolution are present simultaneously.
Other organ systems are uninvolved.
Dermatopathology: Superficial or deep, perivascular or interstitial mixed cell infiltrate, wedge-shaped. Atypical cells may comprise 50% of infiltrate. Type A: large CD30+, atypical histioid lymphocytes with abundant cytoplasm and convoluted nucleus. Type B: smaller CD30–, atypical lymphocytes with cerebriform nuclei. Type C: large CD30+ cells form sheets resembling cutaneous anaplastic large cell lymphoma (CALCL)
Differential diagnosis: Based on typical histology and immunohistochemistry, lack of systemic involvement by history and physical examination.
Course: May remit in 3 weeks or continue for decades. In 10–20% of patients, lymphomatoid papulosis is preceded by, associated with, or followed by another type of lymphoma: MF, Hodgkin disease, or CD30+CALCL. May persist despite systemic chemotherapy for concurrent lymphoma.
No treatments have proved consistently effective. Topical agents include glucocorticoids and carmustine (BCNU). Electron-beam irradiation, PUVA. Retinoids, methotrexate, chlorambucil, cyclophosphamide, cyclosporine, and interferon-α2b, none with lasting effect
Cutaneous Anaplastic Large Cell Lymphomas (CALCLs)
ICD-9: M9714/3 ICD-10: 84.43
CALCLs are cutaneous lymphomas consisting of large tumor cells that express CD30 antigen and have no evidence or history of lymphomatoid papulosis, MF, or other types of CTCL.
They occur in adults and present as solitary, reddish to brownish nodules and tumors, which frequently tend to ulcerate (Fig. 21-14).
Figure 21-14. Anaplastic large cell lymphoma A solitary violaceous, reddish nodule on the forearm of a 46-year-old male patient. Histopathology revealed nonepidermotropic anaplastic mononuclear cells, most of which were of the CD4+, CD30+ phenotype. The lesion was excised and there was no recurrence.
The nodular infiltrates are nonepidermotropic, and neoplastic cells show an anaplastic morphology. At least 75% of the neoplastic cells are CD30+ and additionally express the CD4+ phenotype.
CALCLs have a favorable prognosis with a disease-related 5-year survival rate of 90%.
Treatment is radiotherapy, but successful treatment with PUVA in combination with interferon-α has been reported.
Cutaneous B Cell Lymphoma ICD-9: 202.80 ICD-10: C85.1
A clonal proliferation of B lymphocytes can be confined to the skin or more often is associated with systemic B cell lymphoma. Rare. Comprise 20% of all cutaneous lymphomas.
Occurs in individuals >50 years.
Crops of asymptomatic nodules and plaques, red to plum color (Fig. 21-15) with a smooth surface, firm, nontender, cutaneous, or subcutaneous.
Figure 21-15. Cutaneous B cell lymphoma Smooth, cutaneous, and subcutaneous nodules on the lower leg. One is ulcerated. They were asymptomatic and firm and were the first signs of B cell lymphoma.
Primary cutaneous follicle center cell lymphoma, primary cutaneous marginal zone lymphoma, and primary cutaneous large B cell lymphoma of the leg are special defined entities.
Dermatopathology: Dense nodular or diffuse monomorphous infiltrates of lymphocytes usually separated from the epidermis by a zone of normal collagen (“grenz zone”). B cell-specific monoclonal antibody studies facilitate differentiation of cutaneous B cell lymphoma from pseudolymphoma and CTCL and permit more accurate classification of the cell type. Most cases react with CD19, 20, 22, and 79A. Gene-typing studies confirm diagnosis with immunoglobulin gene rearrangement.
Patients should be investigated thoroughly for nodal and extracutaneous disease; if found, bone marrow, lymph node, and peripheral blood studies will show morphologic, cytochemical, and immunologic features similar to those of the cutaneous infiltrates.
Management: Consists of x-ray therapy to localized lesions and chemotherapy for systemic disease.
Kaposi Sarcoma (KS) ICD-9: 176 ICD-10: C46
KS is a multifocal systemic tumor of endothelial cell origin.
Invariably linked with human herpesvirus type 8 (HHV-8) infection.
Four clinical variants: classic KS, endemic African KS, immunosuppressive therapy-related KS and HIV/AIDS-related KS.
Stage- and variant-dependent localized and/or generalized disease: patches, plaques, and nodules.
Systemic involvement: mainly GI tract.
Responds to radiation and chemotherapy.
DNA of HHV-8 has been identified in tissue samples of all variants of KS. There is seroepidemiologic evidence that this virus is involved in the pathogenesis.
Classification and Clinical Variants
Classic or European KS. Occurs in elderly males of eastern European heritage (Mediterranean and Ashkenazi Jewish). Not so uncommon in eastern and southern Europe; rare in the United States. Males > females. Predominantly arises on the legs but also occurs in lymph nodes and abdominal viscera; slowly progressive.
African-Endemic KS. Between 9% and 12.8% of all malignancies in Zaire. Two distinct age groups: young adults, mean age 35; and young children, mean age 3 years. Males > females. No evidence of underlying immunodeficiency. Four clinical patterns (see below).
Iatrogenic Immunosuppression-Associated KS. Rare. Most commonly in solid-organ transplant recipients as well as individuals treated chronically with immunosuppressive drugs. Arises on average 16.5 months after transplantation. Resolves on cessation of immunosuppression.
HIV/AIDS-Associated KS. In HIV-infected individuals, the risk for KS is 20,000 times than that of the general population, 300 times than that of other immunosuppressed individuals. Despite a decline in recent years, KS is still the most common tumor in male homosexual patients with AIDS. Rarely women may have HIV/AIDS-associated KS. Associated with HIV infection, rapid progression, and extensive systemic involvement. At the time of initial presentation, one in six HIV-infected individuals with KS have CD4+ T cell counts of <500/μL.
KS cells likely are derived from the endothelium of the blood/lymphatic microvasculature. Initially not a true malignancy but rather a widespread reactive polyclonal proliferation in response to angiogenic molecules. Later becomes monoclonal. KS lesions produce factors that promote their own growth as well as the growth of other cells, but it is not known how HHV-8 induces/promotes proliferation of endothelial cells.
Mucocutaneous lesions are usually asymptomatic but are associated with significant cosmetic stigma. At times lesions may ulcerate and bleed easily. Large lesions on palms or soles may impede function. Lesions on the lower extremities that are tumorous, ulcerated, or associated with significant edema often give rise to moderate-to-severe pain. Urethral or anal canal lesions can be associated with obstruction. GI involvement rarely causes symptoms. Pulmonary KS can cause bronchospasm, intractable coughing, shortness of breath, and progressive respiratory failure.
Skin Lesions. KS most often begins as an ecchymotic-like macule (Figs. 21-16 and 21-19). Macules evolve into patches, papules, plaques (Figs. 21-16 to 21-18), nodules, and tumors that are violaceous, red, pink, or tan and become purple-brownish (Figs. 21-16 and 21-17) with a greenish hemosiderin halo as they age. Almost all KS lesions are palpable, feeling firm to hard even when they are in a patch stage. Often oval initially, and on the trunk often arranged parallel to skin tension lines (Fig. 21-20). Lesions may initially occur at sites of trauma, usually in the acral regions (Fig. 21-18). In time, individual lesions may enlarge and become confluent, forming tumor masses. Secondary changes to larger nodules and tumors include erosion, ulceration, crusting, and hyperkeratosis.
Figure 21-16. Classic Kaposi sarcoma Ecchymotic purple-brownish confluent macules and a 1-cm nodule on the dorsum of the hand of a 65-year-old male of Ashkenazi-Jewish extraction. The lesion was originally mistaken for a bruise as were similar lesions on the feet and on the other hand. The appearance of brownish nodules together with additional macules prompted a referral of this otherwise completely healthy patient to a dermatologist who diagnosed Kaposi sarcoma, which was verified by biopsy. There is also onychomycosis of all fingernails.
Figure 21-17. Classic Kaposi sarcoma Black confluent papules on the lower leg that are reminiscent of hyperpigmented stasis dermatitis in chronic venous insufficiency. Involvement of lymphatics has led to pronounced edema of the calf, reminiscent of lipodermatosclerosis. This indicates that the disease process is further advanced.
Figure 21-18. Classic Kaposi sarcoma of the feet Brownish to blue nodules and plaques, partially hyperkeratotic on the soles and lateral aspects of the feet. This is a typical localization of early classic KS.
Figure 21-19. HIV/AIDS-associated Kaposi sarcoma Bruiselike purplish macules, and nodules are present in the face of this 25-year-old male homosexual with AIDS. Early involvement of the face is typical for HIV/AIDS-associated KS.
Figure 21-20. HIV/AIDS-associated Kaposi sarcoma Multiple purplish plaques and nodules on the back of a homosexual AIDS patient. The patient had CD4+ T cell counts <200/μL and marked mucous membrane involvement, Pneumocystis carinii pneumonia, and Candida.
Lymphedema usually occurs on the lower extremities (Fig. 21-17) and results from confluent masses of lesions due to deeper involvement of lymphatics and lymph nodes. Distal edema may initially be unilateral but later becomes symmetric and involves not only the lower legs but also the genitalia and/or face.
Distribution. Widespread or localized. In classic KS, lesions almost always occur on the feet and legs or the hands and slowly spread centripetally (Figs. 21-16 and 21-17). Tip of nose (Fig. 21-19), periorbital areas, ears, and scalp as well as penis and legs may also be involved, but involvement of the trunk is rare. In HIV/AIDS-associated KS, there is early involvement of the face (Fig. 21-19) and widespread distribution on the trunk (Fig. 21-20).
Mucous Membranes. Oral lesions are the first manifestation of KS in 22% of cases; in HIV/AIDS-associated KS often a marker for CD4+ T cell counts of <200/μL. Very common (50% of individuals) on hard palate, appearing first as a violaceous stain, which evolves into papules and nodules with a cobblestone appearance (see Section 33). Lesions also arise on soft palate, uvula, pharynx, gingiva, and tongue. Conjunctival lesions uncommon.
Special Features of African-Endemic KS (non-HIV associated). Four clinical patterns are recognized:
• Nodular type: Runs a rather benign course with a mean duration of 5–8 years and resembles classic KS.
• Florid or vegetating type: Characterized by more aggressive biologic behavior; is also nodular but may extend deeply into the subcutis, muscle, and bone.
• Infiltrative type: Shows an even more aggressive course with florid mucocutaneous and visceral involvement.
• Lymphadenopathic type: Predominantly affects children and young adults. Frequently confined to lymph nodes and viscera, but occasionally also involves the skin and mucous membrane.
General Examination. Viscera KS lesions of the viscera, though common, are often asymptomatic. This is particularly true for classic KS. At autopsy of HIV-infected individuals with mucocutaneous KS, 75% have visceral involvement (bowel, liver, spleen, lungs).
Lymph Nodes. Lymph nodes are involved in half of cases of HIV/AIDS-associated KS and in all cases of African lymphadenopathic type KS.
Urogenital Tract. Prostate, seminal vesicles, testes, bladder, penis, and scrotum.
Lung. Pulmonary infiltrates, particularly in HIV-associated KS.
GI Tract. GI hemorrhage, rectal obstruction, protein-losing enteropathy can occur.
Other. Heart, brain, kidney, and adrenal glands.
Skin Biopsy. Vascular channels lined by atypical endothelial cells among a network of reticulin fibers and extravasated erythrocytes with hemosiderin deposition. In the nodular stage: Spindle cells in sheets and fascicles with mild-to-moderate cytologic atypia, single cell necrosis, trapped RBCs within an extensive network of slitlike vascular spaces.
Imaging. For internal organ involvement.
Diagnosis and Differential Diagnosis
Confirmed on lesional skin biopsy.
Differential Diagnosis. Includes single pigmented lesions: dermatofibroma, pyogenic granuloma, hemangioma, bacillary (epithelioid) angiomatosis, melanocytic nevus, ecchymosis, granuloma annulare, insect bite reactions, and stasis dermatitis.
Course and Prognosis
Classic KS. Average survival, 10–15 years; death usually from unrelated causes. Secondary malignancies arise in >35% of cases.
African-Endemic KS. Mean survival in young adults, 5–8 years; young children, 2–3 years.
Iatrogenic Immunosuppression-Associated KS. Course may be chronic or rapidly progressive; KS usually resolves after immunosuppressive drugs are discontinued.
HIV/AIDS-Associated KS (see also Section 32). HIV-infected individuals with high CD4+ T cell counts can have stable or slowly progressive disease for many years. Rapid progression of KS can occur after decline of CD4+ T cell counts to low values, prolonged systemic glucocorticoid therapy, or illness such as Pneumocystis carinii pneumonia. KS of the bowel and/or lungs is the cause of death in 10–20% of patients. Patients with only a few lesions, present for several months, without history of opportunistic infections, and CD4+ T cell counts >200/μL tend to respond better to therapy and have a better overall prognosis. At time of initial diagnosis, 40% of KS patients have GI involvement; 80% at autopsy. Reduced survival rate in patients with GI involvement. Pulmonary KS has high short-term mortality rate, i.e., median survival <6 months.
The goal of therapy for KS is to control symptoms of the disease, not cure. A number of local and systemic therapeutic modalities are effective in controlling symptoms. Classic KS responds well to radiotherapy of involved sites. African-endemic KS, when symptomatic, responds best to systemic chemotherapy. Immunosuppressive drug-associated KS regresses or resolves when drug dosages are reduced or discontinued. HIV/AIDS-associated KS usually responds to a variety of local therapies; for extensive mucocutaneous involvement or visceral involvement, chemotherapy is indicated. Of course, all this in addition to HAART.
Radiotherapy. Indicated for tumorous lesions, confluent lesions with a large surface area, large lesions on distal extremity, and large oropharyngeal lesions. Cryosurgery. Indicated for deeply pigmented, protruding nodules. Laser Surgery. Pulsed-dye laser effective for small superficial lesion. Photodynamic Therapy. For small superficial lesions.
Electrosurgery. Effective for ulcerated, bleeding nodular lesion. Excisional Surgery. Effective for selected small lesions. Intralesional Cytotoxic Chemotherapy Vinblastine, Vincristine, and Bleomycin.
Single-Agent Chemotherapy with adriamycin, vinblastine, lipid formulations of daunorubicin and doxorubicin. Paclitaxel (Taxol), thalidomide, col-3. Combination Chemotherapy. Vincristine + bleomycin + adriamycin or interferon-α + zidovudine.
• Classic KS: Any of the above.
• African KS: Any of the above.
• Immunosuppression-related KS: Reduction in immunosuppression, replacement of calcineurin inhibitors by rapamycin.
• HIV/AIDS-related KS: Any of the above, preferably liposomal anthracyclines intravenously plus HAART.