Fatal CD8+ Epidermotropic Cytotoxic Primary Cutaneous T-Cell Lymphoma with Multiorgan Involvement

Abstract

A 70-year-old woman presented with a 3-month history of two ulcerated erythematous-violaceous nodular lesions over the nose and forehead, respectively. The patient’s history included a similar cutaneous nodule on the glabella diagnosed as pseudolymphoma 2 years ago.At that time, despite the diagnosis of a benign disease, an adequate staging was performed, ruling out any extracutaneous involvement. During hospitalization, multiple purpuric papules developed over the abdomen, and the disease spread to mediastinal lymph nodes, lungs and the central nervous system. Based on the histologic, immunophenotypic and molecular biology findings, a diagnosis of CD8+ epidermotropic cytotoxic primary cutaneous T-cell lymphoma was made. Secondary skin involvement by a CD8+ extracutaneous T-cell lymphoma could not be excluded with certainty, but seemed to be unlikely because of the negativity of the initial workup. The patient died from complications of right femoral artery thrombosis before starting specific polychemotherapy 21 months after onset of the disease. Among primary cutaneous T-cell lymphomas, the CD8+ epidermotropic cytotoxic subset comprises rare, highly aggressive forms characterized by metastatic spread to unusual sites such as the oral cavity, lungs, testis and the central nervous system but usually not to the lymph nodes. These cases seem to be distinct from mycosis fungoides with CD8+ phenotype, which shows a nonaggressive clinical behavior.

Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma

“…1,2,4,8,11,20 These CD8 1 cases generally follow an indolent clinical course similar to that of the more common, classic CD4 1 variants. 1,2,5,8,20,21 The CD8 1 immunophenotypic variant of MF, for example, reported by Dummer et al, 21 is characterized by a slowly progressing course, responsiveness to initial treatment with nontoxic, conservative therapy including topical corticosteroids and UVB or PUVA, similar to cases of classic MF. 8,21 Even with recurrence of disease, response to less aggressive skin-directed treatments, including topical chemotherapeutic agents, tends to be very good.…”

“…[1][2][3][4][5][7][8][9][10][11][12][13][14][15][16][17] Clinically, the disease manifests as localized or disseminated papules, papules, nodules, and tumors, often with ulceration, hemorrhage, and necrosis, or with superficial hyperkeratotic patches and plaques. [1][2][3][4][5][7][8][9][10][11][12][13][14][15][16][17] Unlike classic MF, patients do not generally have long-standing precursor lesions and do not follow the typical progression through patch-, plaque-, and finally tumor-stage disease, but rather present from the onset with widespread plaque-and tumor-stage disease. 3,9,12 Involvement of mucosal surfaces, and acrally accentuated lesions of the palms and soles, is commonly seen.…”

“…3,4,5,8,9,12 The histologic appearance of primary cutaneous aggressive epidermotropic CD8 1 T-cell lymphoma lesions is variable. Berti et al, 3 who initially characterized the aggressive epidermotropic CD8 1 subtype, describes the histologic features as ''characteristic, if not distinct.''…”

“…[1][2][3][4]8,11 CD56 expression is variable, as is CD2, CD7, and CD5. [3][4][5]8,9,12 Epstein-Barr virus testing generally produces negative results. 1,2 T-cell origin and clonality are demonstrated by TCR-g rearrangement.…”

Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma: Proposed diagnostic criteria and therapeutic evaluation

“…1,3,6,26 Multiagent chemotherapy, particularly doxorubicinbased regimens such as cyclophosphamide, hydroxydoxorubicin, Oncovin, and prednisone (CHOP) and the hyper-cyclophosphamide, vincristine, Adriamycin (doxorubicin), and dexamethasone regimen (hyper-CVAD) that consists of alternating A cycles (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and B cycles (high-dose methotrexate and cytarabine), in 6 to 8 courses, is the most commonly used option for patients with primary cutaneous aggressive CD8 1 epidermotropic T-cell lymphoma. [6][7][8][9][10][11][13][14][15][19][20][21][22][23]25,26 Intensified regimens such as methotrexate, Adriamycin, cyclophosphamide, Oncovin, prednisone, and bleomycin (MACOP-B) have not shown a survival advantage over CHOP. 8,35 Generally, the results of multiagent chemotherapy are unsatisfactory and no available therapy seems to be curative because the response is usually partial, and if complete is associated with rapid relapse, in addition to the high incidence of toxic effects, particularly myelosuppression and opportunistic infections.…”