4.
3.4.
Diagnosis: Peripheral T-cell Lymphoma, unspecified
Cytologically atypical lymphocytes were present in the basal layer of the epidermis in a non confluent pattern (Fig. 3). Extending from the superficial dermis to the base of the biopsy were sheets and infiltrative rows of small and medium sized lymphocytes with complex nuclear irregularities (Fig. 4). Immunohistochemical staining showed these cells to be predominantly T lymphocytes (CD2, 3, 5 and 7 positive) which cross-reacted with both CD4 and CD8. (While there was no loss of surface markers, the cross reactivity with CD4 and CD8 is an aberrant immunophenotype.) Epidermal lymphocytes did not mark with either CD4 or CD8. Scattered CD20 positive B lymphocytes comprised less than 5% of the lymphocyte population. There were two separate foci of strong and definite CD30 staining but in neither of these areas did there appear to be large cell transformation, nor did the cells have the "chunk of coal" appearance of the CD30 positive lymphocytes of lymphomatoid papulosis.
Discussion:
Peripheral T-cell lymphomas are a heterogeneous group of lymphomas that originate from T cells that have completed thymic maturation and are TdT negative. Multiple subtypes of peripheral T-cell lymphoma have been recognized including the cutaneous T-cell lymphoma (CTCL) mycosis fungoides. Additional well-defined subtypes include large cell CD30+ CTCL and large cell CD30- CTCL. However, the majority of patients with T-cell lymphoma cannot be currently classified and are designated as having "peripheral T-cell lymphoma, unspecified" (1). This is a heterogenous group of lymphomas, some of which behave rather aggressively while others are indolent (1).
Cutaneous T-cell lymphoma is a non-Hodgkin's lymphoma characterized by localization of neoplastic T lymphocytes to the skin without evidence of systemic involvement at the time of presentation (2). Mycosis fungoides (MF) and the Sézary syndrome (SS) make up the majority of cases of CTCL. The incidence of CTCL is estimated at 0.5-1 per 100,000 (3) with the incidence of MF at 0.29 cases per 100,000 population per year (4) while the incidence of Lymphomatoid Papulosis (LyP) is 1.2-1.9 cases per 1,000,000 (5). The etiology of CTCL remains unknown, but several causative factors have been proposed including chronic antigen stimulation, viral infections (HTLV-1 and EBV), smoking, medications, and chronic sun exposure (6).
The histologic diagnosis of MF is characterized by an epidermotropic and band-like infiltrate involving the papillary dermis consisting of small, medium and sometime large-sized mononuclear cells with hyperchromatic, cerebriform nuclei (6). Immunohistologically, the malignant cells in MF are usually CD3+, CD4+, CD8-, CD30- and CD45RO+ (6). In this case, neither the histologic features nor the immunophenotype support a diagnosis of mycosis fungoides.
Primary cutaneous CD30+ large T-cell lymphoma presents with one or a few clustered skin lesions consisting of >75% CD30+ blast cells, with no clinical evidence of LyP, no history of MF, and no evidence of extracutaneous disease (6). Patients with primary cutatneous CD30- large T-cell lymphoma rapidly develop plaques or tumors consisting of nodules or diffuse infiltrates of large to medium sized pleomorphic T-cells. Clinically or histologically, this case does not resemble either CD30+ or CD30- large T-cell lymphoma because there were far fewer than 75% CD30+ cells and the CD30- cells were not large lymphocytes.
Lymphomatoid papulosis is a chronic, recurrent, papulonodular eruption that spontaneously resolves with a benign clinical course (2). Histologically, there is superficial and deep dermal invasion by a heterogeneous population of lyphocytes, histiocytes, eosinophiles and atypical small and large-sized lymphocytes. Type A lesions consist of large cells, which resemble Reed Sternberg cells, while type B lesions are made up of smaller lymphoid cells that resemble the atypical lymphocytes in MF (6). While the clinical history is certainly suggestive of lymphomatoid papulosis, neither type-A nor type-B histology to support that diagnosis is seen in the current biopsy material.
This particular patient has a novel presentation of a peripheral T-cell lymphoma that does not fit easily into the classifications of MF, primary cutaneous CD30+ large T-cell lymphoma, primary cutaneous CD30- large T-cell lymphoma, or lymphomatoid papulosis. Clinically, this patient's clinical presentation best resembles that of LyP with erythematous plaques that resolve spontaneously to hyperpigmented patches over the course of weeks to months. However, the clinical appearance of the lesions and the histologic appearance of the biopsy does not support a diagnosis of LyP. Thus, we favor a diagnosis of peripheral T-cell lymphoma, unspecified. This patient was referred to a Hematologist/Oncologist and underwent a staging CT that showed no evidence of systemic involvement and a bone marrow biopsy that showed no evidence of disease. The patient elected to defer treatment and opted to follow the lesions clinically. Six months after diagnosis the lesions continue to spontaneously resolve.
1. Hematology, Basic Principles and Practice 3rd edition. Hoffman R, Benz EJ Jr., Shatill SJ, Furie B, Cohen NJ, Leslie SE, McGlave P, eds., Philadelphia, Churchill-Livingstone, 2000, pg 1319-1320.
2. Willemze R, Kerl H, Sterry W, et al.: EORTC classification for primary cutaneous lymphomas. A Proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer (EORTC). Blood 90:354371, 1997.
3. Willemze, R: Primary cutaneous lymphomas. Curr Opin Oncol 12: 419-25, 2000.
4. Weinstock MA, Horm JW: Mycosis fungoides in the United States: Increasing incidence and descriptive epidemiology. JAMA 260: 42-46, 1988
5. Color Atlas and Synopsis of Clinical Dermatology. 4th edition. Fitzpatrick TB, Johnson RA and Wolff, K, eds., New York, McGraw-Hill, 2001, pg 522.
6. Siegel RS, Pandolfino T, Guitart J, Rosen S, Kuzel TM,: Primary Cutaneous T-Cell Lymphoma: Review and Current Concepts. J Clin Oncol 18(15):2908-2925, 2000.
My thanks to Drs. Paul A. Klekotka, Pamela Kirschner Weinfeld Michael
H. Heffernan for their assistance in the preparation of this case
