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Next-generation sequencing performed on peripheral blood was negative for pertinent gene alterations. In the recent fifth edition of the WHO, these subtypes are listed separately within the hierarchical structure of PCTCLs, with the term ‘pcPTCL NOS’ being reserved for rare cases that do not fit under any other described entity.1 In contrast, the 2022 International Consensus Conference (ICC) classification system does not include pcPTCL-NOS in its diagnostic framework.3 At the outset of the patient’s clinical course, MF was considered in the differential diagnosis; however, this case lacks several defining features seen in MF. According to the WHO classification, a diffuse or nodular dermal infiltrate, sometimes extending to the subcutis, is the defining histological finding in pcPTCL-NOS.1 In contrast, classic MF is characterised by epidermotrophism of small to medium-sized cells with cerebriform nuclei, sometimes forming Pautrier microabscesses.2 While some cases of transformed MF have been associated with the appearance of a CD20 component, recent studies suggest that dense CD20 component is more commonly attributable to a reactive B-cell population instead of true aberrant CD20 expression by T-lymphomatous cells.2 In contrast, aberrant CD20 expression has been documented in about a fifth of cases of pcPTCL-NOS.1 4 In our case, the neoplastic population showed true coexpression of CD3 and CD20 as well as T-cell receptor clonality, supporting the diagnosis of pcPTCL-NOS. [...]our case showed loss of pan T-cell markers CD2 and CD7 and a high Ki-67 proliferation rate, a pattern more consistent with pcPTCL-NOS. Peripheral T-cell lymphomas unspecified presenting in the skin: analysis of prognostic factors in a group of 82 patients.
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Correspondence to Dr Danielle R Rinck; [email protected]
Introduction
Primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS) is a group of T-cell lymphomas that does not fit the criteria of other primary cutaneous T-cell lymphomas (PCTCLs) defined by the WHO. The immunophenotype of the neoplastic T-cells can vary, with some cases showing aberrant expression of CD20. The diagnosis is exceedingly rare, and the prognosis is poor.1
Case report
An elderly female patient with a complex medical history, including peripheral artery disease and chronic wounds secondary to venous stasis, presented with worsening right lower extremity wounds despite outpatient antibiotic treatment (figure 1). She developed hypotension, hypoxia and leukocytosis concerning for sepsis and was admitted for intravenous antibiotic therapy. She was noted to have a generalized rash during her admission consisting of fixed, discrete pink plaques on her trunk and extremities. A skin biopsy was recommended; however, the patient was discharged with a plan for close outpatient follow-up. Unfortunately, she missed her outpatient visit and then presented a month later with acute kidney injury, worsening rash and multipressor shock requiring intubation and sedation. Her rash had coalesced and focally ulcerated; she had also developed discrete tumours (figure 2). Punch biopsies were obtained for more definitive evaluation.
Histopathology revealed a superficial to deep dermal sheet-like infiltrate composed of medium to large abnormal lymphoid cells with irregular nuclear contours. The neoplastic cells extended to the subcutis (figure 3). By immunohistochemistry, the neoplastic cells were positive for CD3, CD5 and CD43 and showed aberrant CD20 expression. They stained dim/subset variable for CD25 and PD-1, subset dim granular for perforin and scattered (rare positive cells) positive for BCL6 (5%). The neoplastic cells stained negative for CD2, CD4, CD7, CD8, CD10, CD19, CD21, CD23, CD30, CD56, CD79a, PAX-5, TCR-delta, TIA-1 and granzyme B. Ki-67 proliferation index was high (approximately 90%) (figure 4). In situ hybridization for Epstein-Barr virus encoded RNA was negative. The immunohistochemical positivity for both CD3 and CD20 was unexpected and raised the differential of both a T-cell and a B-cell neoplasm. T-cell receptor (TCR) gamma gene rearrangement was positive in peripheral blood and skin, confirming T-cell origin. B-cell receptor immunoglobulin heavy chain (IGH) gene rearrangement PCR was negative. Concurrent cytogenetics of the peripheral blood showed an abnormal complex female karyotype with several numerical and structural aberrations including an unbalanced translocation between chromosomes 1 and leading to gain of 1q, and gain of odd chromosome numbers such as trisomies 5, 7 and 15.
The diagnosis of pcPTCL-NOS was made after excluding other entities, as described by the investigations performed above. Concurrent flow cytometry of the peripheral blood was significant for a population of T-cells (3% analyzed events) coexpressing CD5, CD26 and CD279 and showing aberrant CD20 expression. These neoplastic T-cells were negative for CD2, CD7, CD4, CD8, CD13, CD33, CD34, CD56, CD117, CD25, CD30 and TRBC1. These results were consistent with minimal involvement in peripheral blood by the patient’s primary cutaneous T-cell lymphoma. Next-generation sequencing performed on peripheral blood was negative for pertinent gene alterations. The patient received systemic therapy with one cycle of liposomal doxorubicin but unfortunately passed away 2 weeks after admission due to complications of sepsis.
Discussion
Mycosis fungoides (MF) is the most common form of PCTCL worldwide, associated with a favorable prognosis.2 Other forms of PCTCLs are rare and can carry unfavorable prognoses with aggressive clinical courses. In the recent fifth edition of the WHO, these subtypes are listed separately within the hierarchical structure of PCTCLs, with the term ‘pcPTCL NOS’ being reserved for rare cases that do not fit under any other described entity.1 In contrast, the 2022 International Consensus Conference (ICC) classification system does not include pcPTCL-NOS in its diagnostic framework.3
At the outset of the patient’s clinical course, MF was considered in the differential diagnosis; however, this case lacks several defining features seen in MF. Histopathologically, the presence of large pleomorphic lymphoid cells with high-grade cytology arranged in sheets more strongly favors pcPTCL-NOS. According to the WHO classification, a diffuse or nodular dermal infiltrate, sometimes extending to the subcutis, is the defining histological finding in pcPTCL-NOS.1 In contrast, classic MF is characterised by epidermotrophism of small to medium-sized cells with cerebriform nuclei, sometimes forming Pautrier microabscesses.2
While some cases of transformed MF have been associated with the appearance of a CD20 component, recent studies suggest that dense CD20 component is more commonly attributable to a reactive B-cell population instead of true aberrant CD20 expression by T-lymphomatous cells.2 In contrast, aberrant CD20 expression has been documented in about a fifth of cases of pcPTCL-NOS.1 4 In our case, the neoplastic population showed true coexpression of CD3 and CD20 as well as T-cell receptor clonality, supporting the diagnosis of pcPTCL-NOS. Moreover, our case showed loss of pan T-cell markers CD2 and CD7 and a high Ki-67 proliferation rate, a pattern more consistent with pcPTCL-NOS.
Clinicopathological correlation is essential in establishing the diagnosis of pcPTCL-NOS. Our patient’s focal lower extremity wounds rapidly progressed to diffuse plaques and ulcerating tumors over a matter of weeks, a clinical course that aligns with pcPTCL-NOS.1 4 In comparison, MF usually follows an indolent progression with slowly growing lesions over years to decades.2 While pcPTCL-NOS most often presents in the sixth decade of life, cases have been documented in the pediatric population.1 5 The prognosis of pcPTCL-NOS is generally poor with a mean survival rate of 27 months to 5.6 years.1 6 7 Rituximab has been administered as a chemotherapeutic agent in rare cases with aberrant expression of CD20.4 There were plans to add rituximab to our patient’s treatment, but given her overall critical illness, she passed away prior.
In conclusion, this case highlights an exceedingly rare instance of pcPTCL-NOS with aberrant CD20 expression and an aggressive clinical course. Aberrant expression of B-cell markers in T-cell lymphomas presents diagnostic challenges to pathologists and highlights the importance of integrating histopathologic, immunophenotypic, molecular, clonality and clinical data to make an accurate diagnosis. Greater awareness of such atypical presentations may aid in making earlier diagnoses which can guide prompt management.
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References1 World Health Organization. Primary cutaneous peripheral t-cell lymphoma, nos. In: WHO classification of tumours: haematolymphoid tumours. 5th edn. 11. International Agency for Research on Cancer, 2022. Available: https://tumourclassification.iarc.who.int/chaptercontent/63/216
2 Jullié M-L, Carlotti M, Vivot A, et al. CD20 Antigen May Be Expressed by Reactive or Lymphomatous Cells of Transformed Mycosis Fungoides. Am J Surg Pathol 2013; 37: 1845–54. doi:10.1097/PAS.0000000000000091
3 Campo E, Jaffe ES, Cook JR, et al. The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee. Blood 2022; 140: 1229–53. doi:10.1182/blood.2022015851
4 Kempf W, Mitteldorf C, Battistella M, et al. Primary cutaneous peripheral T‐cell lymphoma, not otherwise specified: results of a multicentre European Organization for Research and Treatment of Cancer (EORTC) cutaneous lymphoma taskforce study on the clinico‐pathological and prognostic features. Acad Dermatol Venereol 2021; 35: 658–68. doi:10.1111/jdv.16969
5 Bekkenk MW, Vermeer MH, Jansen PM, et al. Peripheral T-cell lymphomas unspecified presenting in the skin: analysis of prognostic factors in a group of 82 patients. Blood 2003; 102: 2213–9. doi:10.1182/blood-2002-07-1960
6 Pileri A, Agostinelli C, Fuligni F, et al. Primary cutaneous peripheral T-cell lymphoma not otherwise specified a rare and aggressive lymphoma. J Eur Acad Dermatol Venereol 2018; 32: e373–6. doi:10.1111/jdv.14942
7 Tolkachjov SN, Weenig RH, Comfere NI. Cutaneous peripheral T-cell lymphoma, not otherwise specified: A single-center prognostic analysis. J Am Acad Dermatol 2016; 75: 992–9. doi:10.1016/j.jaad.2016.06.011
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