Cutaneous mycobacterial spindle cell pseudotumor: a potential mimic of soft tissue neoplasms.

A 55-year-old man with scleroderma treated with prednisone and etanercept presented with enlarging sporotrichoid nodules on the forearm. Microscopically, there were large circumscribed dermal and subcutaneous nodules of spindled and epithelioid cells, resembling a spindle cell neoplasm. Small foci of neutrophils were also present, and a subsequent Ziehl-Neelsen stain highlighted beaded acid-fast bacilli in the interstitium. Tissue culture demonstrated Mycobacterium chelonae. Cutaneous mycobacterial spindle cell pseudotumor is an exceedingly rare lesion, with only 6 previously reported cases. Although these included patients with autoimmune disease receiving immunosuppressive therapy, this is the first case reported in association with a tumor necrosis factor alpha inhibitor, etanercept. Furthermore, this represents the first mycobacterial spindle cell pseudotumor described in association with M. chelonae. Mycobacterial spindle cell pseudotumor should be considered in the differential diagnosis of cutaneous spindle cell proliferations, especially in immunocompromised patients.

Flow cytometric evaluation of skin biopsies for mycosis fungoides.

Multicolor flow cytometry (FC) is indispensable for lymphoma diagnosis and classification, but its utility in evaluating skin biopsies for mycosis fungoides (MF) is not well established. We describe the largest series to date of skin biopsies evaluated by FC for MF (n = 33), and we compare the flow cytometric results with the histologic, molecular, and clinical findings. Abnormal T-cell populations were identified by FC in 14 of 18 patients (78%) having histologically confirmed MF and in no patient whose histology was negative or indeterminate for MF (n = 14). One patient had histologic, flow cytometric, and molecular findings compatible with MF, but this patient's clinical course was more suggestive of a drug eruption. Fourteen of 15 abnormal T-cell populations showed definitive aberrant expression of at least 2 surface antigens, including CD2 (47%), CD3 (67%), CD4, CD5 (87%), CD7, and CD45 (67%); most cases (67%) had light scatter properties suggesting increased cell size and/or cytoplasmic complexity. The high specificity of FC suggests that it will be a useful adjunct to routine histology in the evaluation of diagnostic skin biopsies for MF.

Expression of prox1, lymphatic endothelial nuclear transcription factor, in Kaposiform hemangioendothelioma and tufted angioma.

Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare tumors mainly occurring in early childhood. Our recent results showed that ectopic overexpression of human Prox1 gene, a lymphatic endothelial nuclear transcription factor, promoted an aggressive behavior in 2 murine models of KHE. This dramatic Prox1-induced phenotype prompted us to investigate immunohistochemical staining pattern of Prox1, podoplanin (D2-40), LYVE-1, and Prox1/CD34 as well as double immunofluorescent staining pattern of LYVE-1/CD31 in KHE and TA, compared with other pediatric vascular tumors. For this purpose, we examined 75 vascular lesions: KHE (n=18), TA (n=13), infantile hemangioma (n=13), pyogenic granuloma (n=18), and granulation tissue (n=13). Overall, KHE and TA shared an identical endothelial immunophenotype: the neoplastic spindle cells were Prox1, podoplanin, LYVE-1, CD31, and CD34, whereas endothelial cells within glomeruloid foci were Prox1, podoplanin, LYVE-1, CD31, and CD34. The lesional cells of all infantile hemangiomas and pyogenic granulomas were negative for Prox1 in the presence of positive internal control. These findings provide immunophenotypic evidence to support a preexisting notion that KHE and TA are closely related, if not identical. Overall, our results show, for the first time, that Prox1 is an immunohistochemical biomarker helpful in confirming the diagnosis of KHE/TA and in distinguishing it from infantile hemangioma and pyogenic granuloma.

The molecular pathogenesis of hereditary ovarian carcinoma: alterations in the tubal epithelium of women with BRCA1 and BRCA2 mutations.

BACKGROUND: BRCA1 or BRCA2 (BRCA1/2)-mutated ovarian carcinomas may originate in the fallopian tube. The authors of this report investigated alterations in BRCA1/2 tubal epithelium to define the molecular pathogenesis of these carcinomas. METHODS: Tubal epithelium was evaluated from 31 BRCA1/2 mutation carriers with gynecologic carcinomas (BRCA CA), 89 mutation carriers who underwent risk-reducing salpingo-oophorectomy (RRSO), and 87 controls. Ki-67 expression and p53 foci (≥10 of 12 consecutive staining cells) were scored by 2 investigators who were blinded to patient designations. Expression levels of p27 and p21 were evaluated within p53 foci. Loss of heterozygosity at the BRCA1/2 mutation site was evaluated in microdissected p53 foci and tubal neoplasms. RESULTS: Background tubal proliferation as measured by Ki-67 staining was increased in the BRCA1 RRSO group (P = .005) compared with the control group. Women who had BRCA1/2 mutations had more p53 foci identified per tubal segment than women in the control group (P = .02). Levels of p27 were decreased in 12 of 28 p53 foci from women with BRCA1 mutations and in 0 of 16 p53 foci from controls (P = .002). There was no loss of the wild type BRCA1/2 allele in 5 tested p53 foci. Tubal neoplasia lost the wild type allele in 6 of 6 foci (P = .002). CONCLUSIONS: The current results suggested a model of tubal carcinogenesis in women with BRCA1/2 mutations. Increased proliferation occurred globally in at-risk tubal epithelium. A mutation in the tumor protein p53 gene TP53 with clonal proliferation and loss of p27 occurred before neoplastic proliferation. Loss of the wild type BRCA1/2 allele occurred with neoplastic proliferation and before invasion.

Expanding the clinicopathologic spectrum of palisaded encapsulated neuroma.

Palisaded encapsulated neuroma (PEN; solitary circumscribed neuroma) is a benign, morphologically characteristic cutaneous or mucosal neuroma. Most are solitary lesions on the face, neck or oral mucosa. Histologically, the majority appears as dermal nodules of Schwann cell-rich fascicles, with or without distinctive encapsulation. To further expand on the existing literature regarding this neuroma, we herein describe three PENs with unique clinical and histopathologic features. All occurred on the acral skin, a rarely described site. Furthermore, one exceptional patient presented with multiple PEN on the bilateral hands, biopsies of which showed a prominent plexiform architecture. Awareness that PEN may occur on acral skin, may rarely present as multiple lesions, and recognition of the plexiform variant is important because PEN may histologically mimic other peripheral nerve sheath tumors. Additionally, misdiagnosis may have significant clinical implications.

Atypical neurofibroma of the skin and subcutaneous tissue: clinicopathologic analysis of 11 cases.

BACKGROUND: Neurofibroma (NF) is a relatively common cutaneous tumor, which typically presents little diagnostic difficulty. Occasionally, however, pleomorphic cells may be present in NF raising consideration of other neoplasms like malignant peripheral nerve sheath tumor (MPNST). METHODS: This study examines the clinicopathologic and immunohistochemical features of 11 dermal and subcutaneous 'atypical' NF. RESULTS: 9/11 (82%) atypical NF were from females, aged 8-70 years. One patient had neurofibromatosis-1. Most presented on the extremities or trunk. The atypical cells had large hyperchromatic, irregular nuclei, and were arranged in a distinct lamellar or fibrillar pattern. Some tumors were hypercellular, but marked density characteristic of MPNST was not observed. All were nonplexiform. Mitoses were mostly absent. The pleomorphic cells expressed S-100 protein. All were negative for p53. MIB-1 was negative in 7/10 (70%) and stained only rare cells in 3 (30%). Epithelial membrane antigen (EMA) and p16 expression were variable. Of six patients with available follow-up, no tumor recurred and none developed malignancy (range 6-63, mean 33 months). CONCLUSIONS: Superficial atypical NF, while morphologically unusual, has no apparent association with neurofibromatosis-1 or short-term risk of recurrence or malignant transformation. Awareness of this variant is important in order to avoid misdiagnosis of a more aggressive neoplasm.

Histiocyte-rich pleomorphic mastocytoma: an uncommon variant mimicking juvenile xanthogranuloma and Langerhans cell histiocytosis.

An 11-year old Caucasian female with a remote history of urticaria pigmentosa presented with a neck mass. A biopsy demonstrated a large intradermal nodule composed of unusually large epithelioid mast cells, including a prominent subset with bi-lobed and multi-lobed nuclei. By immunohistochemistry, the cells expressed CD117 (C-Kit), mast cell tryptase, CD68, and CD25, and were negative for CD163, CD1a, and S-100, confirming the diagnosis of mastocytoma. Equally prominent was an admixed infiltrate of CD68 and CD163-positive xanthomatous histiocytes that included Touton-type giant cells. Eosinophils were abundant. At 7 months follow-up, there was no recurrence of the lesion following complete excision. However, given the unusual cytologic features, close clinical observation is warranted, as the long-term biologic potential of mastocytoma with this degree of cytologic atypia is uncertain. Awareness of this unusual morphologic variant is also important as the histologic features may mimic such childhood neoplasms as juvenile xanthogranuloma and Langerhans cell histiocytosis.

Diagnostic implications of podoplanin expression in peripheral nerve sheath neoplasms.

By using the D2-40 antibody, we have observed podoplanin expression in Schwann cells and perineurial cells. Podoplanin expression has not been well characterized in peripheral nerve sheath tumors. Because neoplasms of neural crest lineage, including peripheral nerve sheath and melanocytic neoplasms, may share histologic and immunohistochemical characteristics, we evaluated podoplanin and S-100 expression in these lesions to determine the usefulness of podoplanin as a diagnostic marker. Diffuse podoplanin and S-100 expression was observed in 16 (76%) of 21 classical schwannomas, 6 (100%) of 6 cellular schwannomas, and 3 (75%) of 4 epithelioid malignant peripheral nerve sheath tumors (EMPNSTs). Podoplanin was expressed in 3 (7%) of 43 neurofibromas, 16 (21%) of 75 spindle cell MPNSTs (SMPNSTs), and 1 (10%) of 10 spindle cell melanomas but was absent in conventional melanoma. Only rare neurofibromas and SMPNSTs showed strong coexpression of podoplanin and S-100. These results suggest diffuse podoplanin expression or coexpression of podoplanin and S-100 is limited to schwannoma and EMPNST and may be useful in the evaluation of these neoplasms.

Collagen-rich variant of benign epithelioid peripheral nerve sheath tumor of the skin.

Schwannoma and neurofibroma account for the majority of cutaneous benign peripheral nerve sheath tumors and usually pose little diagnostic difficulty in their classic forms. In rare instances, however, benign peripheral nerve sheath tumors may display epithelioid morphology and lack otherwise usual features of schwannoma or neurofibroma, making classification difficult. These unusual changes may prompt consideration of other benign neoplasms or a malignancy. Benign epithelioid peripheral nerve sheath tumor (BEPNST) is a somewhat non-specific term recently proposed to describe these neoplasms of imprecise histogenesis. Also diagnostically challenging, rare BEPNST with unusual arrangements of extracellular collagen have been described and reported as neuroblastoma-like schwannoma and collagenous spherulosis. We report a unique case of cutaneous BEPNST with a peculiar arrangement of abundant extracellular collagen, different than the previously observed patterns. Specifically, the neoplastic cells in this tumor were nearly obscured by the collagen, which formed large nodules and compressed the majority of the few remaining tumor cells to the periphery of the lesion. This excessive collagen production emphasizes the importance of adequate sampling to ensure a correct diagnosis.

Lymphomatoid papulosis with CD1a+ dendritic cell hyperplasia, mimicking Langerhans cell histiocytosis.

Although CD1a+ dendritic cells (DC) in cutaneous T-cell lymphomas (CTCL) have been well documented, the presence of large numbers of DC within lymphoid infiltrates can pose a diagnostic difficulty. We present a case of a 70-year-old man with a 3-year history of recurrent red papules and plaques on the extremities and trunk that was referred to our institution, with the diagnosis of Langerhans cell histiocytosis. Skin biopsies showed a wedge-shaped cellular infiltrate in the superficial and deep dermis consisting of two cell populations. Most prominent were clusters of epithelioid cells with grooved nuclei and abundant eosinophilic cytoplasm, which stained with antibodies to CD1a and S-100. A second, less prominent population of atypical lymphocytes, some with enlarged, hyperchromatic and convoluted nuclei, were intermixed. The latter were positive for CD30, CD3 and CD5 and negative for CD20, CD34, CD68, ALK-1 and TdT. T-cell receptor gene rearrangement studies confirmed a clonal T-cell population, which with the clinical history was consistent with the diagnosis of lymphomatoid papulosis. While previous studies have shown an increased density of dermal DC in CTCL, we believe that this represents the first report of an unusually florid DC proliferation mimicking Langerhans cell histiocytosis and masking a lymphoproliferative disorder.

A case of hereditary xerocytosis diagnosed as a result of suspected hypoglycemia and observed low glycohemoglobin.

Hereditary xerocytosis is a primary erythrocyte disorder in which a defect in the erythrocyte membrane leads to potassium efflux from the cell. An osmotic shift of water from the intracellular compartment follows, resulting in decreased deformability of the cell, increased membrane rigidity, hemolysis, decreased average duration of erythrocyte survival, and reticulocytosis. The condition is inherited as an autosomal dominant trait. In this publication, we report the case of a patient who presented with a vague history compatible with hypoglycemia and was found to have a low glycohemoglobin level. Further workup led to a diagnosis of hereditary xerocytosis in this patient and in other members of the family. This case illustrates the importance of understanding the underlying variables that affect the results of all commonly used glycohemoglobin assays, including determination of hemoglobin A(1C) and how primary red-cell disorders may alter its value.