Extensive polymorphic eruption and lymphocytosis in a 56-year-old male—A difficult diagnosis!

Abstract

A 56-year-old male presented with a 5-month history of a pruritic, papular truncal rash with partial response to oral steroids. He reported no systemic symptoms. Initial differential diagnosis included dermatitis herpetiformis, drug-induced rash, a viral exanthem and lymphomatoid papulosis. Multiple skin biopsies were inconclusive, demonstrating a normal epidermis with mixed B-cell and T-cell dermal lymphohistiocytoc infiltrate. A skin biopsy for direct immunofluorescence was negative.

Laboratory investigations revealed mild iron deficient anaemia and CT Thorax Abdomen Pelvis (CT TAP) and colonoscopy confirmed diverticulosis. The patient responded minimally to oral doxycycline, topical clobetasol proprionate and antihistamines.

After 18 months he developed rapid extensive skin involvement with atypical targetoid polymorphic plaques on his limbs, pink coalescing urticated plaques with a geographical border on his trunk (Figure 1a), and ecchymosis of the anterior shoulders (Figure 1b). Fixed, annular, scaly plaques were evident on the dorsum of his hands (Figure 2a) and bilateral thighs (Figure 2b). This was associated with severe itch, fatigue and dyspnoea. Investigations revealed a lymphocytosis (44.7 × 10̂⁹/L) thrombocytopenia (72 × 10̂⁹/L), anaemia (Hb 9.4 × 10̂⁹/L) and atypical lymphocytes on blood film. CT imaging confirmed widespread lymphadenopathy.

A skin biopsy was done (Figure 3a,b).

The rapid deterioration in our patient after 18 months with extensive cutaneous involvement, in association with systemic symptoms, widespread lymphadenopathy and lymphocytosis progressed the differential diagnosis to include Sezary syndrome or transformed mycosis fungoides (T-MF). Clinically the patient was not erythrodermic and did not meet Sezary syndrome diagnostic criteria⁴ and no Sezary cells were identified in the skin, blood, or lymph nodes. Regarding T-MF, the patient did not progress through the patch-plaque stages of MF and skin biopsy did not reveal features of MF such as epidermotropism or pautrier microabscess. There was a patchy expression of CD30+ cells but significantly less than 25% of the infiltrate required to meet the diagnostic criteria of T-MF.⁵

The atypical T-cell population and T-cell clonality identified on multiple BM, LN and skin biopsies resulted in a suspected diagnosis of leukemic dissemination of peripheral T-cell lymphoma not otherwise specified (PTCL NOS), but formal classification remained challenging. PTCL NOS is a heterogeneous group of aggressive nodal and extranodal T-cell lymphomas that are not characterized by any known clinicopathological criteria.⁶

Following expert hematopathology review the histology, molecular results and immunophenotypic studies were repeated. Among the BM, LN and skin specimens three TFH markers, namely CD10, BCL6 and PD1, were collectively identified thus confirming a diagnosis of peripheral T-cell lymphoma with a TFH phenotype of suspected cutaneous origin.

Confirmation of the identical clonal T-cell population from skin biopsies 18 months previous, when the patient had no extracutaneous findings, in addition to the positive TFH markers, confirmed the diagnosis of pcPTCL-TFH with extracutaneous dissemination.

Until recently, the clinicopathological features of pcPTCL-TFH were poorly characterized and based on case reports.^7-9 The French Study Group of Cutaneous Lymphoma Network,³ recently defined the clinical, pathological and molecular features of pcTFH-PTCL. Included in their findings of 18 patients, with male predominance and a median age of 66 years, was the potential for an aggressive clinical course with systemic involvement in a subset of patients. Cutaneous presentation is predominantly widespread nodules or papules with an absence of erythroderma that occurs without nodal or extracutaneous involvement at initial staging.³ Histological findings should include dense dermal CD4⁺ T-cell proliferations with a variable proportion of B cells and absence of epidermotropism. Immunohistochemistry studies must demonstrate at least two TFH markers CD10, CXCL13, PD1, ICOS and BCL6.³

Unfortunately, the patient's condition rapidly deteriorated and he developed primary refractory disease with minimal response to both cyclophosphamide, doxorubicin, etoposide, vincristine and prednisolone (CHOEP) and dose-dense brentuximab vedotin with ifosfamide-carboplatin-etoposide (DD-BV-ICE) chemotherapy and the patient died.

This case highlights the difficult diagnosis of pcPTCL-TFH, the potential for a protracted but aggressive evolution and the important role of dermatology in diagnosing and monitoring of such patients.

Dr. Berbie Byrne was involved in assessment, diagnostic work up and clinical management of the patient. Performed the literature review on pcPTCL-TFH, compiled the data regarding investigation of the patient's diagnostic work up. Prepared and wrote this quiz up. Replied to authors' comments and resubmitted manuscript. Dr. Marion Leahy assisted in assessment and management of the patient. Reviewed literature review. Contributed to write up and reviewed each edit of the manuscript. Obtained and summarised histology slides. Dr. Kevin Molloy reviewed patient clinical findings and diagnostic work up. Summarised key points in diagnostic work up of the patient. Professor Mary Laing primary dermatology physician in the management of the patient. Involved in analysing data regarding patient's complex diagnostic work up. Reviewed script and edited script. Corresponding author.

The authors declare no conflict of interest.

The patient in this manuscript's wife gave written informed consent for participation in the study and the use of their deidentified, anonymized, aggregated data and their case details (including photographs) for publication. Ethical approval: not applicable.