Peripheral T cell lymphoma: not otherwise specified.

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of hematological tumors originating from mature T cells, which constitutes less than 15% of all non-Hodgkins lymphomas in adults. Primary cutaneous PTCL-not otherwise specified (NOS) represent a subgroup of PTCLs with no consistent immunophenotypic, genetic or clinical features. PTCL-NOS frequently has an aggressive course with a tendency for systemic involvement, however, a well-defined therapeutic and prognostic approach has not been outlined yet. We report a case of PTCL-NOS with multiple cutaneous lesions in a young adult male with an emphasis on the treatment modality used.

What was known?

Peripheral T cell lymphoma-NOS is a type of cutaneous T cell lymphoma primarily affecting the skin and usually seen in elderly males.

Introduction

Peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) account for 26% of all (PTCLs) and represent the largest subtype among them.[1] Skin is common site of presentation (10.1%) of an otherwise systemic disease, but very rare examples of true primary cutaneous PTCL-NOS have been reported.[2] The prognosis of PTCL-NOS presenting in skin has an unfavorable prognosis with an exception of CD3+ CD4+ CD8− phenotype presenting with localized skin lesions.[3] Our patient presented to us with multiple skin lesions without extracutaneous involvement and a similar immunophenotype. We started him on oral methotrexate 25 mg once weekly and PUVA thrice weekly and significant improvement was observed.

Case Report

A 26-year-old male patient presented to us with an 8 years history of red, scaly lesions over the body. Initially these started as small raised lesions on the right arm, which gradually increased in size and was associated with scaling and hair loss. Over a period of 5-6 months similar lesions appeared on the trunk and extremities, which were associated with occasional itching. Patient had no systemic symptoms or significant family history.

On examination, patient appeared well-built with multiple erythematous papules and plaques scattered over the abdomen, back and proximal extremities. These papules and plaques were surmounted with large adherent white scales. The involved areas showed a loss of hair with focal areas of atrophy [Figures 1 and 2]. No lymphadenopathy, organomegaly were noted on palpation.

Figure 1

Erythematous plaque with large white scales, areas showing “cigarette paper” wrinkling and loss of hair seen on the abdomen

Figure 2

Erythematous plaque with multiple areas of focal atrophy and scaling seen on the left upper arm

Pertinent laboratory tests were normal except lactate dehydrogenase (LDH), which was raised (489 U/L).

Histopathological examination revealed hyperkeratosis, epidermal atrophy with vacuolar degeneration of basal keratinocytes and melanin incontinence into the dermis [Figure 3]. Dense infiltration by atypical lymphocytes with hyperchromatic nuclei and folded nuclear membrane were seen in the upper dermis [Figure 4]. Numerous ectatic blood vessels were present amidst the lymphoid infiltrate. Mild epidermotropism was present. These features were suggestive of cutaneous T cell lymphoma. Further immunohistochemical analysis by flow cytometry confirmed it to be PTCL-NOS, as the tumor cells expressed CD3, CD2, CD5 and CD4 and were immunonegative for CD20, CD8 and CD30. Mib-1 labeling index was <5%. To rule out systemic involvement computed tomographic scans of neck, chest and abdomen were carried out, which showed normal study with no evidence of enlarged lymph nodes.

Figure 3

Photomicrograph showing hyperkeratosis, epidermal atrophy with dense infiltration by atypical lymphocytes in the upper dermis. Mild epidermotropism present (H and E, ×100)

Figure 4

Photomicrograph showing atypical lymphocytes with hyperchromatic nuclei and folded nuclear membrane were seen in the upper dermis (H and E, ×400)

Patient was treated with oral methotrexate 25 mg once weekly and PUVA thrice weekly for the past 7 months and his cutaneous lesions have flattened markedly [Figure 5a and b].

Figure 5

(a and b) Marked improvement in the lesions after 8 months of treatment with PUVA and methotrexate

Discussion

PTCL-NOS are a heterogeneous group of nodal and extranodal mature T cell lymphomas, which are not defined by any of the recognized clinico pathological entities.[4] In a large international survey, PTCL-NOS represented 4% of all NHLs and constituted the largest group of T cell neoplasms in western countries.[4] In a study carried out by Burad et al. on PTCLs in south India, they found that among the PTCLs, PTCL-NOS was the most common subtype and it was similar to the frequency observed in Far East and western countries.[1]

According to World Health Organization-European Organization for Research and Treatment of Cancer classification, PTCL-NOS is categorized under primary cutaneous lymphomas with aggressive clinical behavior. They show a higher incidence in middle aged to elderly male individuals with a male:female ratio of 2.5:1.[5] Risk factors for PTCL-NOS have not been clearly identified, however, the causative role of smoking, immunosuppression, chemical substances such as solvents, pesticides and infections with Epstein Barr virus cannot be ruled out.[4]

Primary cutaneous PTCL-NOS are clinically heterogeneous, varying from localized to generalized plaques or nodules commonly associated with constitutional symptoms (B symptoms). Mild anemia, thrombocytopenia, elevated LDH, hypereosinophilia and pruritus are common associations. On relapse, they may be associated with symptoms of systemic lymphoma.[45]

Diffuse, nodular or band like infiltrate of atypical lymphocytes occur in the dermis. Medium to large sized pleomorphic or immunoblast like T cells are present in variable numbers. Epidermotropism is generally mild or absent.[5] Immunophenotype analysis is an important diagnostic method for PTCL-NOS. Most common phenotype is CD4+, CD 8+ (CD4>CD8) and CD30±. In a study done by Bekkenk et al., they found that a favorable outcome was noticed in cases with CD3+ CD4+ CD8− phenotype and with a clinical presentation of localized skin lesions.[3] A similar phenotype was found in our patient, but clinically he had multiple skin lesions, which were asymptomatic and mimicked other common dermatological conditions. Routine investigations were not suggestive of a specific diagnosis. He was also of a younger age group and had no positive risk factors. Hence, a skin biopsy was taken, which revealed a diagnosis of PTCL-NOS and this was further confirmed by immunohistochemistry.

Our patient was treated with PUVA therapy thrice weekly in addition to methotrexate 25 mg once a week. These regimes have been individually mentioned in the literature, but are not a commonly used combination therapy in PTCL-NOS. It has proved its effectiveness in this case as significant clinical improvement was achieved within a short time. Patient is on regular follow-up since last 7 months and there is no evidence of relapse of the disease.

The proposed Prognostic Index for PTCL-NOS (PIT) uses the following four independent survival predictive factors: Age >60 years, impaired performance status, elevated LDH, bone marrow involvement. The 5 years survival rate of PTCL-NOS ranges from 25% to 45%.[6] Hence, this type of lymphoma requires prompt diagnosis and vigilant monitoring of progression since it is a life-threatening disease.[7]

What is new?

Peripheral T cell lymphoma may present in younger individuals and can mimic common dermatologic disorders. Combination of oral Methotrexate and PUVA therapy has been proven effective in our patient.