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Biomedical subjects

Cynthia M Magro

Publications and source records attributed to Cynthia M Magro.

At least 19 recordsLinked to original sources

Cribriform tumors of the skin: CD38 expression distinguishes from histologic mimics in a multi-institutional series.

Cribriform tumor of the skin (formerly primary cutaneous cribriform carcinoma/primary cutaneous cribriform apocrine carcinoma) is a rare adnexal neoplasm of uncertain malignant potential. Recent studies have identified recurrent co-deletion of the long arm of chromosomes 6 and 9 and CD38 overexpression as potential diagnostic features, but their sensitivity and specificity remain incompletely defined. We identified 11 cribriform tumors with classic morphologic features, including several previously reported molecular characterized cases and additional unpublished cases, from multiple institutions. CD38 immunohistochemistry was performed on all tumors and compared with a panel of morphologic mimics, including adenoid cystic carcinoma (n = 8), digital papillary adenocarcinoma (n = 8), eccrine/apocrine adenomas (n = 7), hidradenoma (n = 2), and endocrine mucin-producing sweat gland carcinoma (n = 3). SNP array analysis was available in nine cases. Patients had a median age of 47 years with a slight female predominance (64%). Tumors commonly involved the extremities and ranged from 0.3 to 2.0 cm. Histologically, all cases demonstrated a well-circumscribed dermal neoplasm of bland epithelial cells arranged in cribriform architecture with characteristic thread-like intraluminal bridging, without high-grade features. CD38 expression was identified in 9/11 cases (82%), typically with moderate-to-strong diffuse cytoplasmic staining. All morphologic mimics (n = 28) were CD38 negative. Recurrent chromosomal deletions involving 6q and/or 9q were identified in 7/8 (88%) successfully tested cases. Two morphologically classic cribriform tumors lacked CD38 expression, including one with confirmed 6q/9q codeletion, while one CD38-positive case lacked detectable genomic copy number alterations. These findings further support cribriform tumors as a molecularly distinct, low-grade adnexal neoplasm characterized by recurrent 6q/9q deletions and frequent CD38 expression. CD38 appears to be a useful adjunctive diagnostic marker with high specificity among the selected mimics tested, although its sensitivity is incomplete, and absence of staining does not exclude the diagnosis.

Adnexal tumors↗

Cutaneous vascular deposition of C5b-9 and its role as a diagnostic adjunct in the setting of diabetes mellitus and porphyria cutanea tarda.

BACKGROUND: The cutaneous lesions of diabetes mellitus (DM) and porphyria cutanea tarda (PCT) exhibit distinctive microvascular changes including basement membrane zone thickening and lamellation, morphologically appearing as hyaline-like alterations of the vessel wall. Immunofluorescence demonstrates homogeneous mantles of immunoglobulin in the microvasculature. The staining intensity is variable and in some cases can closely approximate those immunofluorescent changes seen in photoaged skin. OBJECTIVE: The purpose of this study was to establish an association between the microvascular changes seen in the skin from patients with DM and PCT and the presence of C5b-9 deposition, potentially defining the C5b-9 assay as an additional diagnostic adjunct. METHODS: Routine light microscopy and immunofluorescence studies were conducted on skin biopsy specimens from 14 patients with cutaneous manifestations of DM and 17 patients with PCT. The immunofluorescence profile included IgG, IgM, IgA, C3, C3d, C4d, and C5b-9. RESULTS: Fourteen of 14 DM and 17 of 17 PCT skin biopsy specimens revealed extensive granular and homogeneous vascular deposition of C5b-9; a similar pattern was observed for C3d and C4d. Control specimens from patients without DM and PCT, where C5b-9 was not an expected immunoreactant, were negative. Positive controls were cases of vasculitis, scleroderma, and dermatomyositis without DM and PCT where C5b-9 deposition was expected. C5b-9 deposition was observed and was of lesser magnitude than that encountered in patients with PCT or DM. LIMITATIONS: We were unable to obtain detailed clinical information on some of the diabetic patients in regards to significant extracutaneous vascular complications. In addition, a correlation between hemoglobin 1 Ac levels and the extent of C5b-9 deposition could not be ascertained as the serum levels for hemoglobin 1 Ac were unknown. CONCLUSION: Granular and homogeneous deposits of C5b-9 in vessels, along with homogeneous deposits of immunoglobulin within the blood vessels, are characteristic immunofluorescence findings in patients with DM and PCT. In regards to potential mechanisms of C5b-9 deposition, decreased metabolism of C5b-9 due to glycosylation of CD59 in the setting of DM and activation of complement by irradiated porphyrins in PCT are proposed. The extent of C5b-9 deposition suggests that this complex may play a pathogenetic role in the evolution of microvascular injury in patients with DM and PCT.

Adult↗

The role of anti-endothelial cell antibody-mediated microvascular injury in the evolution of pulmonary fibrosis in the setting of collagen vascular disease.

We encountered 16 patients with connective tissue disease in whom pulmonary fibrosis developed. Routine light microscopic, ultrastructural, and direct immunofluorescent analyses were conducted, and circulating antibodies, including those of endothelial cell derivation, were assessed using indirect immuno-fluorescence and Western blot assays. Underlying diseases were dermatomyositis, scleroderma, mixed connective tissue disease, sclerodermatomyositis, Sjögren syndrome, rheumatoid arthritis, and anti-Ro-associated systemic lupus erythematosus. Antibodies to one or more Ro, RNP, Jo 1, OJ, and/or nucleolar antigens were seen in all cases and antiphospholipid antibodies in half. All biopsies revealed microvascular injury in concert with intraparenchymal fibrosis; in some cases, there were corroborative ultrastructural findings of microvascular injury. Patterns of fibroplasia represented nonspecific interstitial pneumonitis and usual interstitial pneumonitis. We noted IgG, IgA, and/or complement in the septal microvasculature. In 6 cases with available serum samples, indirect immunofluorescent endothelial cell antibody studies were positive and Western Blot studies showed reactivity of serum samples to numerous endothelial cell lysate-derived proteins. Pulmonary fibrosis, a recognized complication of systemic connective tissue disease, develops in connective tissue disease syndromes with pathogenetically established immune-based microvascular injury at other sites. A similar mechanism of antibody-mediated endothelial cell injury may be the basis of the tissue injury and fibrosing reparative response.

Animals↗

Cytomegalovirus-associated cutaneous vasculopathy and scleroderma sans inclusion body change.

Viruses have long been held to be of pathogenetic importance in the evolution of autoimmune connective tissue disease. We describe 7 adults who developed cutaneous connective tissue disease stigmata in temporal association with recent cytomegalovirus (CMV) infection but without the classic cytopathic changes of CMV infection. We examined 7 adults with clinical presentations encompassing cutaneous vasculitis in 4 and scleroderma in 3. In all 7 patients, there was either IgM seropositivity for CMV and/or CMV DNA isolation from peripheral blood. Although no CMV inclusions were seen, in situ hybridization studies revealed very focal CMV RNA transcript expression with localization mainly to the endothelium. The patients with vasculitis treated with ganciclovir had improvement or resolution of symptoms, whereas only 1 patient with scleroderma received antiviral therapy, without benefit. Another scleroderma patient responded to infliximab therapy. Abortive/partial CMV reactivation can be associated with a syndrome complex mimicking and/or triggering a primary immune-based cutaneous microvascular injury syndrome. Antiviral therapy appears to be of therapeutic value in those cases associated with active necrotizing vasculitic changes. The role of tumor necrosis factor alpha blockers in scleroderma cases temporally associated with CMV infection requires further evaluation.

Adult↗

Idiopathic pulmonary fibrosis related to endothelial injury and antiendothelial cell antibodies.

Mechanisms underlying idiopathic pulmonary fibrosis are not well understood. This paper presents data supporting the hypothesis that microvascular endothelial cell injury and antiendothelial cell antibodies play roles in human idiopathic pulmonary fibrosis. Serologic and pathologic features of 40 patients diagnosed with idiopathic pulmonary fibrosis were evaluated. All patients had open lung biopsies indicating either usual or nonspecific interstitial pneumonitis. All biopsies had morphologic evidence of microvascular injury to the endothelium, and direct immunofluorescence testing revealed variable deposition of IgG, IgM, or IgA within septal microvasculature suggestive of humorally mediated microvascular injury. Ultrastructural studies revealed changes of endothelial cell injury and necrosis and evidence of repetitive episodes of microvascular injury characterized by basement membrane zone collagen deposition and lamellation. Serum samples demonstrated reactivity to multiple endothelial cell antigenic epitopes, and indirect immunofluorescent testing demonstrated a prominent pattern of fluorescence in pulmonary endothelial cell preparations. Serum samples were positive in 37/40 patients for antiphospholipid antibodies with one fourth having positive lupus anticoagulant tests accompanied by thrombotic episodes. In patients with idiopathic pulmonary fibrosis, Factor VIII levels and C-reactive protein levels were also elevated, supporting the presence of endothelial cell injury and inflammation. These data underscore a potential role for immune-based microvascular injury in the evolution of usual or nonspecific interstitial pneumonitis and indicate that those patients have evidence of microvascular injury and endothelial cell necrosis. The high prevalence of antiphospholipid antibodies in these patients may lead to an inherent thrombophilic tendency.

Adult↗

C3d and the septal microvasculature as a predictor of chronic lung allograft dysfunction.

Studies have shown a potential role for humoral rejection in the evolution of lung graft dysfunction, apparently based on antibodies without human leukocyte antigen specificity. The correlation between extent of C4d deposition with clinical status further illustrates the importance of humoral immunity. Our study examines the potential value of C3d as a further diagnostic adjunct. C3d deposition was examined in lung allograft specimens using frozen tissue indirect direct immunofluorescence (IIF) and avidin biotin immunohistochemical applied to paraffin embedded tissue. Intermediate/extensive amounts of C3d using IIF and immunohistochemical (IH) methodologies correlated with chronic graft dysfunction; IIF C3d deposition was associated with septal and bronchial wall fibrosis (p < 0.0001). Weak/absent amounts of IIF and IH C3d correlated with clinical stability (p < 0.0001). Higher levels of C3d by IH were more sensitive than by IIF as a bronchiolitis obliterans syndrome determinant. C3d and C4d deposition using immunofluorescence and IH were correlated (p < 0.00001). C3d deposition appears prognostically significant. Higher tissue expression of C3d mark chronic graft dysfunction/persistent graft failure following transplantation. The close correlation between C3d and C4d lends credence to the role of humoral allograft rejection as a pulmonary graft dysfunction contributing factor. C3d by IH manifests higher sensitivity but similar specificity compared to C3d by IIF.

Capillaries↗

The application of photodynamic therapy in the treatment of metastatic endobronchial disease.

BACKGROUND AND OBJECTIVE: We utilized photodynamic therapy (PDT) for palliation of metastatic endobronchial tumors employing sensitization with synthetic porphyrin, application of non-thermal light, and endoscopic debridement of necrotic tumor. STUDY DESIGN/MATERIALS AND METHODS: Nine patients with symptomatic endobronchial metastasis from carcinomas of the colon(3), breast(3), kidney(2), and tongue(1) received PDT. RESULTS: After two PDT treatments, patients showed substantial response, which was complete in all but one. One patient had perioperative complications and expired 2 days after developing massive hemoptysis during tumor debridement. Patient survival was 6.38 months (mean) and 4.2 months (median). Most patients died from advanced metastatic disease. One patient with metastasis limited to the airway is still alive 24 months following endobronchial presentation. CONCLUSIONS: PDT ameliorates symptoms of metastatic airway obstruction, is easy to apply, has low morbidity and improves the quality of life.

Adult↗

T-cell prolymphocytic leukemia: an aggressive T cell malignancy with frequent cutaneous tropism.

BACKGROUND: T-cell prolymphocytic leukemia (T-PLL), formerly categorized as T-cell chronic lymphocytic leukemia, is a rare and aggressive hematologic malignancy. Although the skin is characteristically involved, it is not a well-recognized entity in the dermatologic literature. METHODS: Six cases of cutaneous T-PLL are presented from a clinical, light microscopic, and phenotypic perspective. RESULTS: The patient population comprised 2 women and 4 men, with a mean age of 69.8 years. The disease was associated in all with skin involvement with facial preference; edema, purpura, and lesional symmetry were characteristic. The skin biopsies demonstrated a largely non-epidermotropic angiocentric lymphocytic infiltrate with accompanying hemorrhage. The cells showed irregular- to reniform-shaped nuclei with small nucleoli and eosinophilic rims of cytoplasm. Phenotypic studies revealed three prevailing profiles: CD4 dominant in 4, CD8 dominant in one, and co-expression of CD4 and CD8 in one. CD3 loss was seen in one case. All expressed T-cell leukemia 1 (TCL-1) and CD7; cutaneous lymphocyte antigen expression was discernible in a dot-like perinuclear array. All cases tested excluding one expressed TCL-1 and CD52. In two cases tested, T-cell receptor beta rearrangements were observed. Cytogenetic studies demonstrated a paracentromeric chromosome 14 inversion. Polysomy 8 and MYC amplification was seen in one case, manifesting an aggressive clinical course. Four patients died from their disease within 18 months of diagnosis. LIMITATIONS: Cytogenetic MYC amplification, FISH, and TCR beta studies were conducted on each of 2 cases, respectively, due to limitations of tissue block samples and/or peripheral blood. cMYC translocation studies were conducted on 3 of the 6 cases, again due to limitations imposed by the tissue samples on the cases. The last case was recently diagnosed and, therefore, long-term follow-up is not possible. CONCLUSION: T-PLL is a distinctive post-thymic T-cell malignancy with frequent cutaneous tropism. A diagnosis is possible in almost all cases based on characteristic clinical, light microscopic, phenotypic, and cytogenetic features. While a chromosome 14 inversion is highly characteristic, additional inherent cytogenetic differences, such as trisomy 8 with CMYC over-amplification, may account for some case to case variation in clinical course.

Aged↗

Malignant adnexal neoplasms.

Malignant cutaneous adnexal neoplasms are one of the most challenging areas of dermatopathology. Tumors of the pilosebaceous apparatus can occur as single-lineage neoplasms or may manifest as complex proliferations with multilineal differentiation patterns including not only the germinative component of the hair bulb, the inner or outer root sheath epithelium and the sebaceous gland and duct, but also the sweat duct components that relate to the apocrine secretory apparatus which empties into the follicle near the follicular bulge. Eccrine and apocrine neoplasms present a bewildering array of morphologies, which often defy precise classification. The purpose of this review is to discuss in detail the malignant neoplasms of the cutaneous adnexae and their benign and prognostically indeterminate mimics.

Diagnosis, Differential↗

Unusual variants of malignant melanoma.

A potential diagnostic pitfall in the histologic assessment of melanoma is the inability to recognize unusual melanoma variants. Of these, the more treacherous examples include the desmoplastic melanoma, the nevoid melanoma, the so-called 'minimal-deviation melanoma,' melanoma with prominent pigment synthesis or 'animal-type melanoma,' and the malignant blue nevus. Also problematic are the unusual phenotypic profiles seen in vertical growth phase melanomas; these include those tumors whose morphological peculiarities mimic cancers of nonmelanocytic lineage and those melanomas that express aberrant antigenic profiles not commonly associated with a melanocytic histogenesis. Metaplastic change in melanoma, balloon cell melanoma, signet-ring cell melanoma, myxoid melanoma, small cell melanoma and rhabdoid melanoma all have the potential to mimic metastatic and primary neoplasms of different lineage derivations. Abnormal immunohistochemical expression of CD 34, cytokeratins, epithelial membrane antigen, and smooth muscle markers as well as the deficient expression of S100 protein and melanocyte lineage-specific markers such as GP100 protein (ie HMB-45 antibody) and A103 (ie Melan-A) also present confusing diagnostic challenges. In this review, we will discuss in some detail certain of these novel clinicopathologic types of melanoma, as well as the abnormal phenotypic expressions seen in vertical growth phase melanoma.

Antigens, Neoplasm↗

Prognosticators of melanoma, the melanoma report, and the sentinel lymph node.

Since the 1960s, the clinical characteristics of melanoma, its histopathology and its biological basis have been the subject of intense study at pigmented lesion clinics in North America, Europe, and Australia. More recently, the immense database of the Melanoma Committee of the American Joint Committee on Cancer (AJCC) has been exploited through complex mathematical models to measure the impact of various histologic features of primary melanomas and of sentinel lymph node deposits and to correlate these parameters with patient survival. The wealth of modern information available to pathologists and clinicians has become of vital interest to the prognostication of the individual patient with melanoma. The purpose of this review is to bring to the attention of anatomic pathologists the essential characteristics of the pathology report for primary cutaneous melanoma in the modern era.

B7-1 Antigen↗

Primary cutaneous lymphoproliferative disorders with dual lineage rearrangement.

We present a series of 15 cases of cutaneous lymphoma and pseudolymphoma with dual lineage rearrangement identified among approximately 1200 cases of cutaneous lymphoproliferative disorders assessed in our 4 institutions during the last 8 years in which the results of both T-cell receptor and immunoglobulin heavy chain rearrangement investigations were available. On the basis of the clinicopathologic information, the cases were retrospectively subdivided into 2 categories: (1) cases with definite features of cutaneous lymphoma or pseudolymphoma (n = 11) and (2) cases with unclassifiable disease (n = 4). The detection of dual genotype in the first group did not influence the final diagnosis; 7 cases represented cutaneous B-cell lymphomas, 3 pseudolymphomas, and 1 case lymphomatoid papulosis. The presence of monoclonal T-cell receptor-gene rearrangements in these cases may be explained either by monoclonal or oligoclonal expansion of exuberant T cells (or B cells in case of lymphomatoid papulosis) or by lineage infidelity. Three patients with unclassifiable disease had several clinical and histopathologic features in common. They were elderly, presented with solitary lesions, were in good general health and histopathologically demonstrated a dense multinodular infiltrate containing approximately an equal number of T and B cells and a high number of histiocytes forming granulomas, with prominent granulomatous features in 2 cases. B cells were either scattered with the infiltrate or formed collections vaguely resembling follicles; Reed-Sternberg-like cells were seen in 2 cases. B cells showed expression neither of immunoglobulin light chain. The T-cell component was represented mainly by small, well-differentiated lymphocytes or slightly pleomorphic cells, with some medium-sized convoluted cells. Epstein-Barr virus was not detected by polymerase chain reaction. The exact classification of these cases is unknown; they differ histopathologically from previously published cases of bigenotypic cutaneous lymphomas. They may merely represent a growth or reactive pattern, but, on the other hand, may be low-grade lymphomas. If so, they may be histopathologically related to cutaneous Hodgkin disease, T-cell/histiocyte-rich large B-cell lymphoma, or composite lymphomas. Further reports are needed to identify these lesions to clarify their nature and biologic potential.

Adult↗

Primary cutaneous CD30+ large cell B-cell lymphoma: a series of 10 cases.

BACKGROUND: White CD30 expression is described in extracutaneous diffuse large B-cell lymphomas, a primary cutaneous B-cell lymphoma (PCBCL) equivalent is not well defined. METHODS: Between June 1999 and July 2002 the authors encountered 10 patients with CD30+ PCBCLs of the large cell type. RESULTS: The patients comprised seven women and three men; five patients were over 80 years of age, all except one presenting with solitary plaques. With the exception of one death from myocardial infarction and one recurrence, all patients are well at a mean follow-up of 23.4 months. Skin biopsies showed a background of T-cell-rich reactive lymphoid hyperplasia in 7 of 10 patients, with variable granulomatous inflammation in 5 cases. The neoplastic large cells were immunoblastic in appearance. In four patients the infiltrate was dominated by large cells. In the remaining patients the reactive infiltrate defined the dominant cell population. The neoplastic cells expressed CD20, CD30, CD43, and BCL-2. In two cases associated with methotrexate therapy, Epstein-Barr virus expression was observed amid the neoplastic cell populace. CONCLUSIONS: CD30+ PCBCL is a distinctive form of B-cell lymphoma presenting in elderly patients and can be associated with a very good prognosis. In some patients the intensity of reactive inflammation obscures the diagnosis. In the authors' experience almost a third of the cases were associated with Epstein-Barr virus infection and methotrexate therapy, suggesting a distinctive association.

Adult↗

Autoimmune-like pulmonary disease in association with parvovirus B19: a clinical, morphologic, and molecular study of 12 cases.

Parvovirus B19, the agent responsible for fifth disease, has been emerging as a significant pathogenetic factor in various acute vasculitic syndromes such as Wegener's granulomatosis, Henoch-Schönlein purpura, and Kawasaki disease. It has also been implicated in more chronic vasculopathic syndromes, specifically in the context of scleroderma and dermatomyositis. The basis of this association is likely multifactorial; implicated mechanisms include the virus's affinity for endothelium, resulting in a state of neoantigenicity through varied mechanisms as well as the induction of tumor necrosis factor alpha, a factor involved in the propagation of ANCA-positive vasculitic syndromes. The authors present a series of 12 patients with interstitial lung disease including idiopathic pulmonary fibrosis, scleroderma-associated pulmonary fibrosis, lymphocytic interstitial pneumonitis, and septal capillaritis. In all cases there was evidence of chronic parvovirus B19 infection based on serologic assessment and the isolation of B19 DNA on lung samples in all patients. Furthermore, in two cases there was in situ localization of B19 RNA and tumor necrosis factor alpha to endothelium and stromal cells. On pathologic examination, there were varying degrees of both septal fibrosis and inflammation along with evidence of septal capillary injury. In those cases categorized as representing either scleroderma or idiopathic pulmonary fibrosis, the immunofluorescent studies showed evidence of anti-endothelial cell antibody formation. The ANCA-associated syndromes were, as expected, negative by fluorescent analysis. Significantly elevated factor VIII levels, a standard serologic index of endothelial cell injury, were seen in four of the six patients tested. The antiphospholipid profile revealed antiphospholipids in 7 of the 11 patients tested. This report highlights a possible causal role for parvovirus B19 in the pathogenesis of select pulmonary disorders.

Adult↗

Subclinical chronic lymphocytic leukaemia associated with a 13q deletion presenting initially in the skin: apropos of a case.

INTRODUCTION: B-cell chronic lymphocytic leukaemia (B-CLL) represents a low-grade B-cell lymphoproliferative disease that is the most common leukaemia in adults. The neoplastic cell is an autoreactive CD5 CD23 B lymphocyte. B-CLL may involve the skin, typically in the context of known disease. We present a case of subclinical B-CLL presenting initially in the skin. CASE REPORT: A 73-year-old male developed a lesion on his right cheek in April 2003 compatible with basal cell carcinoma. The re-excision specimen contained a well-differentiated atypical lymphocytic infiltrate consistent with B-CLL along with residual carcinoma. Subsequent laboratory studies revealed peripheral blood lymphocytosis with smudge cells. A diagnosis was made of Rai stage 0 CLL. Chromosomal studies on peripheral blood showed a deletion at 13q14.3. Excision of a second primary skin carcinoma revealed a squamous cell carcinoma in association with B-CLL that was identical to his previously diagnosed skin involvement. CONCLUSION: This case identifies a cutaneous presentation of subclinical B-CLL. There are two prior reports describing B-CLL presenting initially in the skin. In one case, the infiltrates were incidental on a re-excision specimen. The second report suggests 16% of B-CLL patients have cutaneous manifestations as the first sign of disease.

Aged↗

Lichenoid and granulomatous dermatitis associated with atypical mycobacterium infections.

BACKGROUND: Lichenoid and granulomatous dermatitis defines a distinctive pattern of cutaneous inflammation that may be part of the morphologic spectrum of idiopathic lichenoid reactions such as lichen planus and as well may be seen with lichenoid drug reactions, endogenous T-cell dyscrasias and as a feature of certain systemic diseases especially Crohn's disease and rheumatoid arthritis. RESULTS: We encountered three cases of lichenoid and granulomatous dermatitis in which the basis was one of primary cutaneous Mycobacterium infection. In all three cases acid fast stains revealed pathogenic organisms and as well cultures were positive for Mycobacterium kansasii in one case and Mycobacterium marinum in another. Other features included a prominent perineural and periadnexal lymphocytic infiltrate. CONCLUSIONS: The differential diagnosis of lichenoid and granulomatous dermatitis should also encompass primary cutaneous Mycobacterium infection in addition to the other more characteristic entities associated wtih this distinctive reaction pattern. Infection with Mycobacterium induces a TH1 dominant response which would hence produce an infiltrate.

Adolescent↗

Cutaneous marginal zone B-cell lymphoma in the setting of fluoxetine therapy: a hypothesis regarding pathogenesis based on in vitro suppression of T-cell-proliferative response.

INTRODUCTION: Drugs may be an important cause of atypical lymphocytic infiltration. Oftentimes, these infiltrates are in the context of pseudolymphomata. We report a patient who developed lymphocytoma cutis temporally associated with initiation of fluoxetine therapy that later went on to develop cutaneous marginal zone B-cell lymphoma. The response of peripheral blood lymphocytes to fluoxetine and other drugs was examined in an attempt to ascertain the potential role for drugs in the propagation of these infiltrates. MATERIALS AND METHODS: Routine light microscopic analysis and phenotypic studies were performed on tissue obtained from a skin biopsy. Lymphocyte mitogenic studies were carried out using increasing concentrations of fluoxetine, bupropion, and two anticonvulsants. RESULTS: An initial biopsy was consistent with lymphocytoma cutis. The patient stopped fluoxetine associated with lesional regression. The lesions recurred despite being off fluoxetine; a repeat biopsy was compatible with marginal zone lymphoma. Lymphocyte proliferation assays revealed a suppressive effect on T-lymphocyte proliferation at physiologic concentrations. Other tested drugs did not have a similar suppressive effect. CONCLUSIONS: Fluoxetine may be associated with pseudolymphomata and marginal zone lymphoma. The inhibitory effects on T-lymphocyte function and more specifically T-suppressor function may lead to excessive antigen-driven B-cell proliferation.

Anticonvulsants↗