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Cutaneous Peripheral T-Cell Lymphoma Associated With a Proliferation of B Cells

Ingerlisa W. Mattoch MD, Regan Fulton MD, PhD, Youn Kim MD, Richard Hoppe MD, Roger A. Warnke MD, Uma N. Sundram MD, PhD
DOI: http://dx.doi.org/10.1309/AJCP5W0VOCSVOBRA 810-819 First published online: 1 June 2009

Abstract

Although the new World Health Organization-European Organization for Research and Treatment of Cancer classification focuses on providing uniformity in the diagnosis of cutaneous lymphomas, cutaneous peripheral T-cell lymphoma (PTL) remains a poorly defined subgroup. As follow-up to a study of systemic PTL complicated by a proliferation of B cells, we studied 16 cases of cutaneous PTL that contained morphologically atypical T cells associated with a significant infiltrate of B cells (about 20%–50%). A clonal T-cell receptor γ chain gene rearrangement was present in all cases. In contrast, a clonal immunoglobulin heavy chain gene rearrangement was present in only 1 case. Clinical staging in 14 cases identified systemic involvement in 2. At last follow-up, both patients with systemic involvement had died of disease, and the majority of patients with primary cutaneous disease were alive (11/12). The presence of numerous atypical B cells and T cells caused diagnostic confusion in these cases. Comprehensive pathologic studies, coupled with clinical staging, are necessary for the accurate diagnosis of this unusual manifestation of cutaneous PTL.

Key Words:
  • Peripheral T-cell lymphoma
  • B-cell lymphoma
  • Cutaneous
  • B cells
  • Epstein-Barr virus

The diagnosis of cutaneous T-cell lymphoma (CTCL) is difficult and remains one of the most complex tasks a pathologist or dermatopathologist encounters.1 This complexity is due, in part, to the continual evolution and controversy surrounding the lymphoma classification systems13 and the fact that, in many cases, a correct diagnosis requires adequate clinical correlation and staging.1 The joint World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas resolves much of this quandary by putting forth a uniform and systematic scheme for approaching cases of cutaneous T-cell lymphomas24; however, shortcomings exist even in this comprehensive report. In particular, primary cutaneous peripheral T-cell lymphoma (PTL), which constitutes about 10% of all CTCL, remains a poorly defined and heterogeneous subgroup.5

We describe 16 cases of cutaneous PTL that contained a significant infiltrate of B cells (cutaneous PTL-B). The mixed nature of the infiltrate caused a majority of cases to be diagnosed as B-cell lymphoma, lymphoma not otherwise specified (NOS), or a mixed reactive infiltrate; only 1 case was diagnosed as T-cell lymphoma. The treatment and prognostic implications in making this distinction underscore the importance of recognizing this uncommon histologic manifestation of cutaneous PTL. The purpose of this study was to analyze the clinicopathologic, immunohistochemical, and molecular features of cutaneous PTL-B.

Materials and Methods

Cases

The Stanford University Medical Center Institutional Review Board (Stanford, CA) approved the study. Cases were obtained from the dermatopathology and hematopathology consultation services in the Division of Surgical Pathology, Stanford University Medical Center. The reports of all cases of cutaneous PTL were reviewed, and cases that contained numerous CD20+ B cells were included in the series. Cases in which patients had a diagnosis of mycosis fungoides or angioimmunoblastic T-cell lymphoma (AITL) were excluded. In addition, cases in which the patient was known to have a history of systemic lymphoma at the time of diagnosis of skin lesions were excluded. Clinical follow-up information was obtained from the Stanford University Medical Center Cutaneous Lymphoma Clinic patient files and/or from the patient’s outside treating clinician. Clinical follow-up information was available for 14 of 16 cases Table 1. Standard staging evaluation included complete history and physical examination; computed tomography scans of the thorax, abdomen, and pelvis; bone marrow biopsy or aspirate (if performed); CBC; and laboratory studies, including lactate dehydrogenase. The preliminary findings of these cases were reported previously in abstract form.6

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Table 1

Light Microscopic and Immunohistochemical Studies

Histologic sections were prepared from tissue fixed in 10% formalin, embedded in paraffin, cut at 3- to 4-μm-thick sections, and stained with H&E. Sections were stained for immunohistochemical analysis on a Ventana BenchMark instrument (Ventana Medical Systems, Tucson, AZ) using the biotin-avidin technique in which diaminobenzidine was used as a chromogen.7 The following primary antibodies were used: CD2 (clone AB75, Leica/Vision Biosystems, Bannockburn, IL), CD3 (polyclonal, Cell Marque, Hot Springs, AR), CD4 (clone 1F6, Novocastra [Vector], Newcastle upon Tyne, England), CD5 (clone 4C7, Novocastra), CD7 (clone CD7-272, Novocastra), CD8 (clone C8/144B, DAKO, Carpinteria, CA), CD20 (clone L26, DAKO), CD30 (clone Ber-H2, DAKO), κ light chain (polyclonal, DAKO), λ light chain (polyclonal, DAKO), βF1 (clone 8A3, DAKO), and CXCL13 (clone 53610, R&D Systems, Minneapolis, MN). In cases in which immunohistochemical studies for light chains were not informative, κ and λ in situ hybridization (ISH) studies were performed (Ventana; cases 4, 6, and 12–16). Positive internal or external controls were present for all antibodies. Limited unstained slides precluded a full antibody panel in all cases.

ISH for Epstein-Barr Viral RNA

Epstein-Barr viral (EBV)-encoded small RNA (EBER) was detected from 3- to 4-μm-thick, formalin-fixed, paraffin-embedded tissue sections by ISH using a Ventana BenchMark instrument running a standardized program incorporating deparaffinization, hybridization to the Inform EBER probe cocktail, and staining with ISH iVIEW nitroblue tetrazolium (Ventana Medical Systems). Cases were evaluated for EBV-labeled cells under visible light microscopy, and the number of cells with blue nuclei was visually estimated. In approximately two thirds of the cases studied for EBV (depending on availability of sample), a control hybridization was performed with an oligo-deoxythymidine probe to detect polyadenylated messenger RNA. In addition, an external positive control sample consisting of an EBV+ malignancy (NK/T-cell lymphoma or nasopharyngeal carcinoma) was run with each set of hybridizations.

ISH Analysis for κ/λ Light Chains

When slides were available, κ and λ ISH was performed on formalin-fixed, paraffin-embedded sections. A cocktail of oligonucleotide probes labeled with a fluorescein conjugate (prediluted; Inform Cytoplasmic Immunoglobulin κ and λ, Ventana Medical Systems) was used in the Ventana BenchMark immunostainer. Positive internal or external control samples were used in all assays.

Isolation of DNA

DNA was obtained from formalin-fixed, paraffin-embedded tissue blocks by cutting four to eight 20-μm-thick sections followed by deparaffinization by extracting 3 times in 1.0 mL of xylene or Histoclear (National Diagnostics, Atlanta, GA). The extracted tissue was washed 2 times in 1.0 mL of 100% ethanol and then dried at 65°C. The tissue was resuspended in 2 vol (30 to 250 μL) of a mixture of 200 mmol/L potassium chloride, 40 mmol/L Tris [Tris(hydroxymethyl) aminomethane]-hydrochloride (pH 8.5), 0.1% sodium dodecyl sulfate, and 0.6 mg/mL Proteinase K and incubated at 55°C to 65°C overnight. The sample was then boiled for 8 minutes and centrifuged at 15,000g for 10 minutes, and the DNA-containing supernatant was collected. To evaluate the yield of DNA, a 5-μL aliquot of supernatant was separated by electrophoresis on a 0.8% agarose gel (Invitrogen, Carlsbad, CA), stained with ethidium bromide, and visualized by UV illumination. Based on an estimate of the DNA concentration, the crude extract was diluted with an appropriate volume of reagent-grade water (Teknova, Hollister, CA) and used directly in a polymerase chain reaction (PCR) experiment. Typically, a 1:10 to 1:20 dilution was prepared, and 5 μL was used for the PCR experiment.

T-Cell Receptor γ and Immunoglobulin Heavy Chain PCR Analysis

Cases were evaluated for B- and T-cell clonality using 2 commercially available PCR-based kits that detect clonal rearrangements in the immunoglobulin heavy chain gene (IGH) and T-cell receptor γ chain gene (TCRG), respectively (InVivoScribe Technologies, San Diego, CA). These multiplex PCRs are based on a European collaborative study (BIOMED-2 Concerted Action).8

The PCRs were performed according to the manufacturer’s protocols. Briefly, a 5-mL aliquot of DNA sample was added to 45 mL of each reaction mixture and 1.25 U of AmpliTaq Gold (Applied Biosystems, Foster City, CA). Amplification was carried out in a Perkin-Elmer 9700 thermocycler (Perkin-Elmer Applied Biosystems, Foster City, CA) by initially heating at 95°C for 7 minutes, followed by 35 cycles of 95°C for 45 seconds, 60°C for 45 seconds, and 72°C for 90 seconds. The final step was incubation at 72°C for 10 minutes. Following amplification, 1 mL of PCR product was added to 10 mL of HI-Deionized Formamide (Applied Biosystems) and 1 mL of ROX-250 internal size standard (Applied Biosystems). The mixture was then denatured at 95°C for 5 minutes, chilled on ice for 5 minutes, and resolved by capillary electrophoresis on an ABI 3100 instrument using performance optimized polymer-4 (Applied Biosystems). The data were stored electronically and analyzed using GeneScan analysis software (Applied Biosystems).

The criteria for assigning a clone were as follows: a clone was required to show a distinct peak within the expected size range for a given primer set, with a height exceeding that of the polyclonal background by at least 2-fold. When an IGH primer set yielded 3 or more distinct peaks in the expected size range with heights at least 2-fold greater than the polyclonal background, the results were classified as oligoclonal. Cases with a clonal peak demonstrated by 1 or multiple primer sets were scored as positive. For TCRG, the presence of more than 2 peaks in any combination of primer sets was considered oligoclonal. Cases with polyclonal and/or oligoclonal results were scored as negative.

Results

Clinical Information

The clinical details are summarized in Table 1. Information about clinical manifestations was available for all patients. The mean age at diagnosis was 57.5 years (range, 37–86 years). There was a male predominance (11 men and 5 women). The clinical manifestations were varied and included cutaneous and subcutaneous nodules, plaques, and skin discoloration. Patients had single (12 patients) or multiple (4 patients) lesions; 1 patient had a single lesion, and multiple lesions subsequently developed (case 2). The most common sites involved included the head and neck, trunk, and upper extremities (14/16).

Full clinical staging in 13 of 16 cases identified systemic involvement in 2 patients; staging was not performed in 1 patient (case 13), and staging details are not known for 2 patients (cases 9 and 16). Treatment details were available for 14 of 16 patients. Chemotherapy and/or radiation therapy regimens were pursued for patients with systemic disease and 3 of 11 patients with primary cutaneous involvement. The remaining patients with primary cutaneous involvement were managed as follows: excision and observation, 1; subcutaneous injection/oral modalities, 1; or observation alone, 7.

Follow-up information was available for 14 of 16 patients, with a mean duration of follow-up of 29.5 months (range, 6–61 months). Both patients with systemic involvement died of disease, with a mean follow-up of 8.5 months (6 and 11 months). All 11 patients with primary cutaneous involvement were alive, 8 in clinical remission and 3 with persistent disease. The patient without clinical staging was alive with persistent disease. Follow-up was not available for the 2 cases that also lacked staging details.

Histologic, Immunophenotypic, ISH, and Molecular Studies

The histologic features are summarized in Table 2 and shown in Image 1. The results of immunohistochemical studies, ISH studies for κ and λ light chains and EBV, and molecular studies for B- and T-cell gene rearrangements, are summarized in Table 3.

Image 1

(Case 16) Histologic appearance of cutaneous peripheral T-cell lymphoma with a significant infiltrate of B cells. A, Low-power view showing partly diffuse, partly nodular dense lymphocytic infiltrate occupying full thickness of the dermis (H&E, x4). B, The lymphoid infiltrate shows minimal epidermotropism and folliculotropism; note background increase in small-caliber vasculature (H&E, x20). C and D, High-power views show cytologically pleomorphic lymphoid cells with a range in cell size; many cells contain abundant clear cytoplasm and nuclear membrane irregularities (H&E, C, x60; D, x90).

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Table 2
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Table 3

Histologically, the lymphoid infiltrate in 4 cases showed a superficial and/or deep perivascular/periadnexal pattern, reminiscent of marginal zone lymphoma. Although Uherova et al9 described 8 cases of nodal PTL that morphologically mimicked marginal zone lymphoma, to our knowledge, no one has described this mimicry in skin. In 12 cases, there was a dense, diffuse, or nodular pattern sometimes in a periadnexal distribution, more akin to large B-cell lymphoma (Image 1A). Significant infiltration of the subcutaneous fat was seen in 4 cases, 7 showed focal subcutaneous fat involvement, and 5 showed no subcutaneous fat extension. In the 4 cases with significant subcutaneous fat involvement, 2 cases involved the dermis and 2 cases were based in subcutaneous tissues without evaluable epidermis or dermis. No cases showed fat necrosis or appreciable karyorrhexis. Very focal epidermo-tropism and/or folliculotropism was noted in 5 cases (Image 1B). A vascular proliferation was seen in all cases. All cases contained large lymphoid cells characterized by vesicular chromatin, prominent nucleoli, nuclear membrane irregularities, and a moderate to abundant amount of clear to lightly eosinophilic cytoplasm (Images 1C and 1D). The background cellularity was mixed in most cases, consisting of eosinophils, histiocytes, and/or plasma cells.

By immunohistochemical analysis, all cases showed a mixed population of T cells that expressed CD3 Image 2A and B cells that expressed CD20 Image 2B. Both lineages demonstrated a range in cell size including a subset of large, cytologically atypical cells Image 2C and Image 2D. All cases contained a significant proportion of B cells (ranging from 20% to 50% of the infiltrate) that were not confined to follicles. Comprehensive T-cell immunophenotypic evaluation was possible in 4 cases, with staining for CD2, CD3, CD4, CD5, CD7, and CD8; given the lack of sufficient materials in the remaining cases, only a subset of these markers was tested. Two cases (cases 1 and 13) showed aberrant loss of CD2 and CD5 (minority subset) and CD7 (majority subset). Case 1 represents secondary cutaneous involvement and the disease status for case 13 is not known; based on these results, we postulate that case 13 may represent secondary cutaneous involvement. In the remaining cases tested, only CD7 expression was lost, with cases showing loss in both a minority and majority of the T-cell population. There was a marked increase in T cells that expressed CD4 compared with those that expressed CD8 in a majority of cases tested (12/13). CD30+ large cells ranged from rare numbers of cells (<1%) up to 10% of the infiltrate. The significant numbers of large CD30+ cells, as is usually seen in CD30+ lymphoproliferative disorders, were not present in these cases. βF1+ cells were identified in all 10 cases tested and highlighted the range in T-cell size, marking large cells in all cases. No CXCL13+ cells were identified in 10 cases tested.

Image 2

(Case 16) Immunophenotype of cutaneous peripheral T-cell lymphoma with a significant infiltrate of B cells. A, The lymphoid infiltrate is mostly composed of CD3+ T cells extensively infiltrating full thickness of the dermis (immunoperoxidase, x4). B, A significant infiltrate of CD20+ B cells is admixed (~40% of infiltrate) (immunoperoxidase, x4). C and D, High-power examination shows that the atypical cells of varying size represent CD3+ T cells and CD20+ B cells (C and D, immunoperoxidase, x90).

Amplification and heteroduplex analysis for TCRG and IGH gene rearrangements were performed on all cases. All 16 cases were positive for TCRG gene rearrangements, whereas only 1 of 15 cases tested was positive for IGH gene rearrangements (case 1). Analysis for κ and λ light chains was performed on all cases, 9 by immunohistochemical analysis and 7 by ISH. Of these, 1 case showed κ light chain restriction; these cells showed concentration in B cell–rich areas, and we postulate that they likely represent B cells. No λ light chain restriction was seen. The case with κ light chain restriction was negative for IGH gene rearrangements (case 12).

ISH studies for EBV RNA were positive in 3 of 16 cases, and the number of positive cells showed marked variation, from rare numbers to sheets of positive cells. All positive cells were large. One of the EBV+ cases was also positive for IGH gene rearrangements (case 1). Although materials were not available for double-labeling studies to confirm the lineage of EBV+ cells, the presence of highest EBV expression in B cell–predominant areas suggested that the EBV+ cells were, in fact, B cells. Data were not available to assess whether the EBV+ patients were from EBV-endemic areas or whether they had immunodeficient comorbidities.

Discussion

We report 16 cases of cutaneous PTL complicated by a proliferation of B cells. The diagnosis of T-cell lymphoma was made on morphologic grounds, based on the cytologic atypia of the T-cell population, and was further supported by positive TCRG gene rearrangements in all cases. The diagnostic difficulty of our cases is underscored by the fact that only 1 case was initially suspected to be a T-cell lymphoma (case 16). The presence of a B-cell proliferation resulted in an initial diagnosis of B-cell lymphoma in 3 cases and in indeterminate diagnoses such as “lymphoma, NOS” (5 cases) and “atypical lymphoid infiltrate” favoring a reactive process (7 cases).

The proliferation of numerous large B cells in nodal PTL was previously reported by Higgins et al.10 They studied 14 lymph node cases that exhibited the morphologic appearance of PTL and contained substantial numbers of polytypic large B cells. EBV was present in a majority of cases (10/14). PCR analysis confirmed a clonal rearrangement of the TCRG in 12 of 13 cases tested. Few other authors have described the presence of B cells in CTCL, many of which represented cases of mycosis fungoides.1115 Similar to our findings, the presence of numerous B cells complicated the diagnosis and resulted in misdiagnoses such as a reactive process or T cell–rich B-cell lymphoma. Golembowski et al12 and Förste et al11 examined the nature of the B cells in cases of T-cell lymphoma and demonstrated a polyclonal infiltrate. Based on these results, they suggested a bystander role for the B cells with the possibility that the clonal expansion of T cells in CTCL stimulates emigration of B cells to the skin. The polyclonal nature of the B cells in the majority of our cases supports this hypothesis.

The mixed infiltrates in our cases, with a range in cell size in both B- and T-cell lineages, raises a differential diagnosis that includes T cell–rich large B-cell lymphoma or benign cutaneous lymphoid hyperplasia (CLH). In terms of the subtype of T-cell lymphoma, our cases raise the following differential diagnoses: cutaneous involvement by AITL, subcutaneous panniculitis-like T-cell lymphoma (SPTCL), γδ T-cell lymphoma, and, in confirmed primary cutaneous cases, primary cutaneous CD4+ small to medium-sized pleomorphic T-cell lymphoma.

Primary cutaneous T cell–rich large B-cell lymphoma is rare and not well described.16 Similar to the criteria for lymph nodes, the diagnosis of cutaneous T cell–rich large B-cell lymphoma requires a paucity of large B cells (<10% of the infiltrate) within an abundant background of reactive T lymphocytes. Because all of our cases had more than 20% B cells, none would have met the World Health Organization criteria for this diagnosis. In difficult cases, the diagnosis of cutaneous T cell–rich large B-cell lymphoma can be suggested when the lesion is positive for IGH gene rearrangements and/or shows light chain restriction. Although less sensitive PCR methods have been used in the past, when these lesions have been tested, they have been shown to be negative for TCRG (when performed), making this diagnosis less likely in our cases.1719

CLH may be B-cell rich or T-cell rich (B-CLH and T-CLH, respectively), mimics lymphoma histologically and clinically, and results from entities such as drugs, foreign agents (ie, tattoo, insect bites, and acupuncture), infections, and photosensitivity.18 In the current series, consideration for a reactive process, such as T-CLH or B-CLH, is warranted in many of the cases, especially those with solitary lesions that resolved spontaneously without therapy (cases 5, 7, 10, 12, 14, and 15).18 We concluded that these latter cases represented lymphomas based on the presence of morphologically atypical T cells in combination with positive clonality studies for TCRG.17,18 The indolent clinical course in these cases is akin to other indolent T-cell lymphomas, including mycosis fungoides and primary cutaneous CD4+ small to medium-sized pleomorphic T-cell lymphoma.3,5,13

CXCL13, a marker of germinal center T cells, is useful in separating nodal AITL from nodal PTL, unspecified.20 This is an important diagnostic point, as significant overlap can exist, at least in nodal disease, between PTL and AITL, and both can be complicated by proliferations of large B cells.9,10,21 This marker has also recently been shown to be accurate in the diagnosis of cutaneous involvement by AITL.22 In our study, it proved to be useful to exclude cutaneous involvement by AITL, as all cases tested with this marker were negative.

The finding of fat involvement in some cases raised the possibility of SPTCL. However, in the cases with this finding, the infiltrate also extended to involve the papillary dermis, arguing against this diagnosis.23 In addition, no cases showed fat necrosis or appreciable karyorrhexis, which are findings that are usually present in cases of SPTCL.23

Immunostaining for βF1, a monoclonal antibody to the T-cell β chain antigen receptor, was positive in large cells in all of our cases, further confirming the T-cell phenotype of cutaneous PTL-B.2426 This result also argues against γδ T-cell lymphoma, a provisional entity separated from the general category of cutaneous PTL, which is negative for βF1 in lesional cells.5

The distinction between cutaneous PTL-B and primary cutaneous CD4+ small to medium-sized pleomorphic T-cell lymphoma is the most difficult to make.13 The latter entity contains a dense, diffuse, or nodular infiltrate of small to medium-sized pleomorphic T cells. The lesions typically occur on the face, neck, or upper part of the trunk, and the entity shows a favorable prognosis (estimated 5-year survival, 60%–80%).3,5,13 As a subset of our cases showed clinical and histologic features similar to this entity, we conclude that this subset may indeed represent examples of primary cutaneous CD4+ small to medium-sized pleomorphic T-cell lymphoma, with a concurrent B-cell proliferation, which has recently been reported as a common feature in that entity.13

Comprehensive T-cell immunophenotypic evaluation in our cases revealed mixed results. Only 2 cases demonstrated a clear aberrant immunoprofile, with loss of CD2, CD5, and CD7 expression, a finding that has been described in PTL.27 The remaining cases tested all showed preservation of CD2 (3 cases) and CD5 (6 cases); CD7 expression was lost in 5 of 7 cases tested. The significance of this latter finding is unclear, in the absence of other antigen loss, as loss of CD7 expression can be seen in reactive T-cell infiltrates.28 Based on these results, we conclude that complete immunophenotyping should be pursued in all cases, as the resultant immunoprofile in a subset of cases may be sufficient to raise suspicion for T-cell lymphoma. However, the majority of cases will require molecular diagnostic characterization to confirm the diagnosis.

The presence of dual-lineage rearrangements in cutaneous lymphoproliferative disorders is a documented but rare phenomenon, estimated at approximately 1% of cases.21,29 The significance of this finding is undetermined and may represent a bigenotypic lymphoma, with one result due to lineage infidelity. The other possibility is the presence of 2 distinct monoclonal populations.10,29 All of our cases tested positive for TCRG. However, only 1 case tested positive for IGH (1/16 [6%]). Although information about the accurate interpretation of clonality studies in this context is scant, work from our laboratories10,21 and others19 indicates that while positive B-cell clonality studies are not necessarily unusual in T-cell lymphoma, the reverse (ie, a positive T-cell clonality study in a B-cell lymphoma) is a highly unusual finding. Thus, we believe that the presence of cytologically atypical T cells with a positive TCRG study supports a diagnosis of T-cell lymphoma, even in the setting of a positive IGH result.

Although we did not perform specific double-staining experiments, given limited materials, because EBV expression seemed to be strongest in areas of B-cell predominance, we postulate in our cases that the large EBV+ cells are B cells. This is similar to cases of nodal PTL-B reported by Higgins et al,10 who did perform double-staining experiments. They showed that EBV+ cells also expressed CD20. Of our 3 EBV+ cases, 2 represented secondary cutaneous involvement. This finding is similar to the findings by de Bruin et al,30 which suggested that the presence of EBV+ cells favors a diagnosis of secondary cutaneous involvement by systemic lymphoma, rather than primary cutaneous disease.

Our study highlights the fact that the clinical course and treatment approach of cutaneous PTL, in general, remains heterogeneous (Table 1); other authors have reported this same finding.31,32 Our cases also demonstrate that the distinction between primary cutaneous and systemic disease cannot be made on histologic grounds alone, and correlation with clinical features and staging remains a necessity. This distinction is important because, as our cases show, secondary cutaneous involvement portends a worse prognosis compared with primary cutaneous disease.

The actual incidence of cutaneous PTL-B is not known. We received 230 cases of cutaneous PTL, NOS within the period of case selection. Thus, approximately 7% of our consultation cases represented cutaneous PTL-B. Although this number likely overestimates the percentage of these cases that would be seen on a general pathology service, it may provide some insight into the likelihood of encountering this diagnosis on other consultation services.

We have characterized an unusual histologic manifestation of cutaneous PTL, both primary and secondary, associated with a proliferation of B cells. We believe these cases represent T-cell lymphoma and not B-cell lymphoma based on the cytologic atypia of the T cells present, the positive TCRG, and our experience that a positive T-cell clonality study in a B-cell lymphoma is a highly unusual finding. We concede that a subset of these cases may represent primary cutaneous CD4+ small to medium-sized pleomorphic T-cell lymphoma in patients who had solitary lesions that resolved without therapy. We recommend that a systemic workup be pursued for all patients who receive a diagnosis of cutaneous PTL-B because, as our study shows, patients with secondary cutaneous involvement can have a solitary lesion that is morphologically and immunohistochemically indistinguishable from cases of primary cutaneous disease. To arrive at a secure diagnosis in the setting of a mixed, cytologically atypical B- and T-cell infiltrate, comprehensive pathologic analysis is required, including molecular studies for IGH and TCRG. Furthermore, a complete clinical staging workup and correlation of the histopathologic and ancillary findings with clinical information is necessary.

Acknowledgments

We thank Daniel Arber, MD, for expert review of our manuscript and Anet James for outstanding technical assistance with our photos.

Notes

Upon completion of this activity you will be able to:

  • recognize complex cases of cutaneous peripheral T-cell lymphoma associated with a proliferation of B-cells (cutaneous PTL-B).

  • define the clinical and pathologic features of cutaneous PTL-B.

  • discuss the diagnostic algorithm to arrive at a correct diagnosis of cutaneous PTL-B.

The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit™ per article. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module.

The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Questions appear on p 896. Exam is located at www.ascp.org/ajcpcme.

Footnotes

  • Supported in part by the Department of Pathology, Stanford University.

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