Prominent CD56 expression by damaged and regenerating muscle fibers in the skin.

BACKGROUND: Antibodies to CD56 label natural killer cells as well as tissues with neural and neuroendocrine differentiation. Despite its apparently limited distribution, other conditions may unexpectedly show strong CD56 expression. METHODS: We report three cases to document another setting with strong expression of CD56 in the skin: damaged and/or regenerating muscle fibers. One case of cutaneous lupus erythematosus, one case of lymphomatoid granulomatosis, and one case of a dermal scar adjacent to cutaneous muscle fibers were evaluated with a panel of antibodies, including CD56. RESULTS: All cases showed histopathologic evidence of muscle fiber damage in the setting of lymphocytic infiltration or trauma. All cases showed prominent expression of CD56 by damaged and/or regenerating muscle fibers. The degree of CD56 expression was directly proportional to the proximity to the injury site and inversely proportional to fiber diameter. CONCLUSIONS: Even though CD56 is a useful marker for certain cytotoxic lymphomas and neural/neuroendocrine neoplasms, its expression is not limited to these conditions. Our cases highlight another unexpected example of strong CD56 expression in the skin: damaged and/or regenerating muscle fibers. The growing list of CD56-positive conditions suggests that this marker may not be as specific as initially assumed.

[Pulmonary lymphomatoid granulomatosis: an immunohistochemical and gene rearrangement study].

OBJECTIVE: To study the immunophenotype and gene rearrangement pattern of pulmonary lymphomatoid granulomatosis. METHODS: Nine cases of pulmonary lymphomatoid granulomatosis, included 5 cases of open lung biopsy, 3 cases of lobectomy specimen and 1 case of autopsy, were retrospectively analyzed by immunohistochemistry, in-situ hybridization for Epstein-Barr virus-encoded RNA, immunoglobulin and T-cell receptor gene rearrangement studies. RESULTS: The age of patients ranged from 3 to 59 years. The male-to-female ratio was 3: 6. Histologically, all cases showed lymphocytic infiltration surrounding the blood vessels and in the perivascular areas. Most of these lymphoid cells expressed T-cell marker CD3. There were also variable numbers of CD20-positive B cells. The staining for CD56 was negative. According to the WHO classification, there were 4 cases of grade I , 1 case of grade II and 4 cases of grade III lesions. Six cases had gene rearrangement studies performed and 3 of them demonstrated clonal immunoglobulin gene rearrangement (including 1 of the grade II and 2 of the grade III lesions). No T-cell receptor gene rearrangement was detected. CONCLUSIONS: Pulmonary lymphomatoid granulomatosis may represent a heterogeneous group of lymphoproliferative disorders. Some of the cases show B-cell immunophenotype and clonal immunoglobulin gene rearrangement, especially the grade II and grade lesions. They are likely of lymphomatous nature.

Variation in IL7R predisposes to sarcoid inflammation.

Sarcoidosis is a chronic granulomatous disorder characterized by a massive influx of Th1 lymphocytes. Both naive and memory T cells express high levels of interleukin 7 receptor-alpha (IL7R alpha), encoded by the IL7R gene. The purpose of this study was to investigate the role of the IL7R gene region in susceptibility to sarcoidosis. Six common single-nucleotide polymorphisms (SNPs) spanning IL7R were genotyped and analyzed in 475 sarcoidosis patients and 465 healthy controls. Replication of one significant associated SNP was carried out in 206 independent sarcoidosis patients, 127 controls and 126 patients with Löfgren's disease. The rs10213865 SNP was associated with sarcoidosis (P=0.008), and in silico analysis showed a complete linkage (r(2)=1, D'=1) with a functional nonsynonymous coding SNP in exon 6 (rs6897932, T244I). Combined analysis of 663 individuals with sarcoidosis and 586 controls (homozygous carriers of risk allele, P=5 x 10(-4), odds ratio=1.49 (1.19-1.86)) provided strong statistical support for a genuine association of IL7R with the risk of sarcoidosis. In addition, we report the same trend between variation in the IL7R gene and patients with Löfgren's disease, suggesting that variation in IL7R may confer general risk for developing granulomatous lung disease.

Traumatic Ulcerative Granuloma with Stromal Eosinophilia: CD30 analysis and clonality for T cell receptor gene re-arrangement.

INTRODUCTION: Traumatic Ulcerative Granuloma with Stromal Eosinophilia (TUGSE) is a rare oral ulcerated lesion of uncertain etiology, showing eosinophil-rich granulation tissue, with occasional large atypical CD30 positive mononuclear cells. It had been suggested that it may represent an oral counterpart of cutaneous lymphomatoid papulosis, with a potential to evolve into CD30 + T cell lymphoma OBJECTIVES: To compare TUGSE and non-specific oral ulcers (NSU) clinically, histopathologically and by clonality analysis for T-cell receptor re-arrangement, aiming to determine whether TGUSE with atypical cells is a lymphomatous premalignant condition, and whether therapeutic approach should be radical or conservative. MATERIALS AND METHODS: Retrospective archival analysis included 17 TUGSE and 8 NSU cases. Histopathological parameters included mean eosinophil number per high power field (HPF), presence of infiltration of deep soft tissues and presence of atypical cells. Immuno-morphometry comprised of the mean number of CD30+ atypical cells per HPF. T-cell receptor (TCR) gene rearrangement by polymerase chain reaction (PCR) was performed in all cases showing atypical cells. Clinical and follow up data were retrieved from files. RESULTS: TUGSE showed a significantly higher mean eosinophil number/HPF in comparison to NSU (7.0 + 4.2 cells and 2.3 + 1.72, respectively; p < 0.001). Atypical cells were found in 9 (53%) cases of TUGSE and in only 1 (11%) case of NSU. CD30+ atypical cells were found in 7 (41%) cases of TUGSE and only in 1 (11%) case of NSU. Mean number of CD30+ cells/HPF was 0.23 + 0.19 (range 0 - 0.54 cells/HPF) for TUGSE. In the only NSU case with CD30+ cells, their density was 0.52/HPF. All lesions with atypical cells were polyclonal for TCR. All cases were self-limiting, with no recurrences, after 3-9 years (mean 4.6 years) follow up. CONCLUSIONS: Analysis found no support to the suggestion that TUGSE with atypical cells represents the oral counterpart of lymphomatoid papulosis or predisposes the lesions for a hematolymphoid malignancy. Suggestions for radical therapeutic approach and long-term follow-up are probably unjustified, with no recurrences or malignancy recorded following conservative treatment alone for a period of up to 9 years of follow-up. Staining for CD30 and PCR for TCR gene rearrangement should be reserved only for rare cases with abundant large atypical cells and/or unusual clinical behavior.

Lymphomatoid granulomatosis mimicking interstitial lung disease.

Lymphoid granulomatosis is a rare form of pulmonary angiitis. This case report presents a patient with lymphoid granulomatosis in whom the clinical presentation, radiological features and the partial response to corticosteroid therapy mimicked interstitial lung disease. Lymphoid granulomatosis was only diagnosed at post-mortem examination. The range of reported clinical presentations, diagnostic approaches and outcomes are described.

Proliferation and cellular phenotype in lymphomatoid granulomatosis: implications of a higher proliferation index in B cells.

Pulmonary involvement by lymphomatoid granulomatosis (LYG) is characterized by nodules of a polymorphous lymphoreticular infiltrate with necrosis, angioinvasion, and variable numbers of large, atypical cells. Using combined immunohistochemistry, the authors compared the expression of a marker of proliferation (DNA topoisomerase IIalpha) between B cells, T cells, and histiocytes. Sixteen cases of LYG were stained by combined immunohistochemistry for DNA topoisomerase IIalpha and CD-20, CD-3, CD-68, and CD-57. A proliferation index was determined for B cells, T cells, histiocytes, and natural killer cells by dividing the number of cells with coexpression of DNA topoisomerase IIalpha and CD-20, CD-3, CD-68, or CD-57 by the total number of CD-20+, CD-3+, CD-68+, or CD-57+ cells, respectively. A significantly higher proliferation index was present in B cells compared to T cells, histiocytes, or natural killer cells (p < 0.002). The average proliferation index for B cells was 0.25+/-0.24 (range, 0.00-0.76), for T cells was 0.02+/-0.01 (range, 0.00-0.04), for histiocytes was 0.00+/-0.01 (range, 0-0.02), and for natural killer cells was 0.00+/-0.00 (range, 0.0-0.02). The average proliferation index of CD-20+ cells was greater in grade III LYG (0.36) than in grade II LYG (0.17) or the single case of grade I LYG (0.00). The authors conclude that (1) there is a spectrum of B-cell proliferation in LYG that roughly correlates with histologic grade, (2) T cells, histiocytes, and natural killer cells do not proliferate but are recruited, and (3) the average B-cell proliferation index in grade III LYG is similar to that observed in large cell non-Hodgkin's B-cell lymphomas. These observations provide a possible rationale for the use of chemotherapy for grade III LYG and observation or immunologic adjuvants for LYG with grade I or grade II histology.

[Granulomatous thymitis with stromal amyloidosis]. / Ganulomatoznyi timit s amiloidozom stromy.

In a surgically removed thymus of an 18 year old man granulomatous thymitis with lymphoid follicles, amyloidosis, pseudocysts were observed. Rare occurrence of this pathology, difficulty of the diagnosis, absence of the treatment concept make surgery a method of choice.

Lymphomatoid granulomatosis of the uterine cervix.

Lymphomatoid granulomatosis is an Epstein-Barr virus-driven lymphoproliferative disorder, usually with a prominent pulmonary involvement and occasional extrapulmonary manifestations. Here, we present a case of lymphomatoid granulomatosis confined to the uterine cervix at the initial diagnosis. The disease was preceded by an immunosuppressive condition, namely low-grade lymphoplasmacytic lymphoma treated with chemotherapy. This is the first report of lymphomatoid granulomatosis at this site and emphasizes that it can present at unusual sites, such as the female genital tract in immunosuppressed patients.

Adhesion molecules in lymphomatoid granulomatosis.

The expression of some adhesion molecules of the integrin family and their ligands was investigated in skin biopsies from a patient with lymphomatoid granulomatosis (LG), who at onset presented cutaneous lesions followed by lung and brain involvement. The angiocentric and angiodestructive skin infiltrate consisted mainly of T helper 'memory' cells (CD2+, CD3+, CD4+, CD5+, CD7+, CD45RO+) with a variable expression of activation antigens (CD25-, CD38+, CD71+, HLA-DR+) and 20% Ki67+ (nearly all atypical cells). T cells highly expressed alpha 3 beta 1 and alpha 5 beta 1 integrins, along with integrins of the beta 2 family. A modification of the expression pattern in laminin and collagen IV and an increased expression of tenascin and fibronectin were also observed.