RESUMEN
SMARCA4 and SMARCB1 loss of function has been implicated in many different tumors. The objective of this study was to investigate the loss of BRG1 and INI1 expression in TTF-1 negative neuroendocrine carcinomas to see if they are analogous to small-cell carcinoma of the ovary, hypercalcemic type. The potential role of these tumor suppressor genes in high-grade neuroendocrine carcinoma largely remains unknown. Cases of previously diagnosed Small cell carcinoma (SmCC), Large cell neuroendocrine carcinoma (LCNEC) and Merkel cell carcinoma (MCC) were selected. Immunohistochemical expression patterns for BRG1 and INI1 were interpreted as: intact, hybrid and complete loss of nuclear staining. SmCC and LCNEC cases were divided as TTF-1 positive and TTF-1 negative subsets. One case of TTF-1 negative SmCC (lung) showed loss of SMARCA4(BRG1) expression. Amongst TTF-1 negative LCNEC, one case (lung) showed complete loss of SMARCA4(BRG1) and partial loss of SMARCB1(INI1) and one case (lymph node) had hybrid expression of SMARCA4(BRG1) with intact SMARCB1(INI1) expression. All TTF-1 positive cases and all MCC cases showed intact expression of SMARCA4(BRG1) and SMARCB1(INI1). Our study highlights that SMARCA4(BRG1) is deficient in a subset of NEC. Inactivation of SMARCA4 in a subset of TTF-1 negative neuroendocrine carcinomas especially of pulmonary site can be further studied for their therapeutic response to targeted therapy e.g. EZH2 inhibitors. In addition, our study is the first to show that BRG1 and INI1 expression are intact in MCC and hence the biology of MCC might be completely exclusive of these two tumor suppressor genes.
Asunto(s)
Carcinoma de Células de Merkel/metabolismo , ADN Helicasas/metabolismo , Proteínas Nucleares/metabolismo , Proteína SMARCB1/metabolismo , Factor Nuclear Tiroideo 1/metabolismo , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Carcinoma de Células de Merkel/patología , Carcinoma Neuroendocrino/metabolismo , Carcinoma de Células Pequeñas/metabolismo , Neoplasias Endometriales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de TranscripciónRESUMEN
Warthin tumor is one of the most common benign salivary gland tumors. Overt lymphoma is known to occur in the lymphoid stroma of Warthin tumor. In situ follicular neoplasia is difficult to identify in routine histologic examination of lymphoid tissue and has not been reported in association with Warthin tumor. Our objective is to determine the prevalence of overt malignant lymphoma and in situ follicular neoplasia in Warthin tumor. We conducted a retrospective histological evaluation of 89 sequential Warthin tumor cases with available slides and blocks from the years 2010-2019. Of these, 84 cases were subjected to immunohistochemical testing, while 5 cases had been previously worked up for the suspicion of lymphoma. We identified two additional cases of lymphoid neoplasia associated with Warthin tumor including small lymphocytic lymphoma/chronic lymphocytic leukemia (n = 1) and in situ follicular neoplasia (n = 1) in addition to previously reported case of follicular lymphoma included in this study. The prevalence rate of first-time detected lymphoid neoplasia in Warthin tumor is 3.4%. The prevalence rate of overt lymphoma is 2.2%, while the prevalence of in situ follicular neoplasia is 1.1%. We propose histologic criteria to identify small lymphocytic lymphoma and follicular lymphoma in Warthin tumor. These include a monotonous interfollicular expansion of small lymphocytes and germinal centers composed of a monotonous population of lymphocytes without polarity or tingible body macrophages respectively. It is very important for pathologists to perform a diligent morphological examination and perform immunohistochemistry in suspected cases to identify subtle involvement of Warthin tumor by lymphoma. In patients with involvement of Warthin tumor by in situ follicular neoplasia, concurrent lymphoma in the same tissue and other sites should be considered. Patients without overt lymphoma elsewhere likely have a low risk of progression to follicular lymphoma. The low prevalence of in situ follicular neoplasia in Warthin tumor, combined with the low rate of clinical progression to lymphoma, make routine screening of Warthin tumor for in situ follicular neoplasia unnecessary.
Asunto(s)
Adenolinfoma/patología , Linfoma/epidemiología , Neoplasias Primarias Múltiples/epidemiología , Neoplasias de las Glándulas Salivales/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma/patología , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/patología , Prevalencia , Estudios RetrospectivosRESUMEN
Warthin tumor is one of the most common benign salivary gland tumors. It is unusual and difficult to diagnose follicular lymphoma within the lymphoid tissue of Warthin tumor. We present a rare case of a 69-year-old man with systemic follicular lymphoma initially diagnosed in a Warthin tumor. Lymphomas occurring within Warthin tumors are rare, however, follicular lymphoma is most commonly reported. Because these patients require further treatment depending on the stage of a disease, it is important for a pathologist to review the histology of Warthin tumors diligently to identify occult lymphomas.
Asunto(s)
Adenolinfoma/patología , Linfoma Folicular/patología , Neoplasias Primarias Múltiples/patología , Neoplasias de la Parótida/patología , Anciano , Humanos , MasculinoRESUMEN
OBJECTIVES: Data characterizing the cytogenetic landscape of intravascular large B-cell lymphoma (ILBCL) are limited. Here, we developed a comprehensive karyotypic data set to identify recurrent cytogenetic abnormalities in ILBCL. METHODS: Cases of ILBCL with complete cytogenetic analysis were identified from an institutional database and the literature. The combined data were systematically reviewed for the presence of recurrent abnormalities. RESULTS: Four new cases were identified and combined with 25 karyotypes previously published in the literature. Karyotypes were uniformly complex with a median of 10 aberrations. In total, 72.4% had abnormalities involving chromosome 1, with 31.0% involving rearrangements of 1p13 or 1q21; 58.6% had abnormalities involving chromosome 6, which in almost all cases involved 6q; 34.5% had abnormalities involving chromosome 14, with 27.6% involving rearrangements of 14q32; and 55.2% had abnormalities of chromosome 18, with 37.9% harboring trisomy 18. CONCLUSIONS: Recurrent cytogenetic abnormalities involving chromosomes 1, 6q, and 18 are present in greater than 50% of ILBCL.
Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 18/genética , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 6/genética , Linfoma de Células B Grandes Difuso/genética , Adulto , Anciano , Médula Ósea/patología , Análisis Citogenético , Femenino , Humanos , Cariotipo , Masculino , Persona de Mediana Edad , Síndrome de la Trisomía 18/genéticaAsunto(s)
Células Precursoras de Granulocitos/patología , Leucemia Mieloide/diagnóstico , Células Progenitoras Linfoides/patología , Síndromes Mielodisplásicos/diagnóstico , Enfermedad Aguda , Anciano de 80 o más Años , Linaje de la Célula , Femenino , Humanos , Leucemia Mieloide/sangre , Leucemia Mieloide/complicaciones , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/complicacionesRESUMEN
Cyclin D1 expression, usually absent in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), has been described in the proliferation centers (PC) of some CLL/SLL. The prevalence of this finding is uncertain, as is the explanation for its occurrence and whether these cases have any other unique features. Cyclin D1 immunohistochemical staining was therefore investigated in 57 extramedullary CLL/SLL biopsies. In 6 cases, cyclin D1 immunofluorescence followed by CCND1 fluorescence in situ hybridization (FISH) and PC targeted analysis was performed using a Bioview Duet system. Excluding the prospectively selected cases that had the targeted FISH studies, cyclin D1+ PC were identified in 20% of cases. The cyclin D1+ CLL did not appear pathologically or phenotypically distinctive, though 46% had an interfollicular growth pattern. The cyclin D1+ PCs were SOX11- and lacked CCND1 translocations and gains in 5 of 5 informative cases. The recognition of cyclin D1 expression in PC of a significant minority of CLL/SLL can be a diagnostic aid and should not lead to the diagnosis of focal mantle cell lymphoma.
Asunto(s)
Ciclina D1/genética , Centro Germinal/metabolismo , Leucemia Linfocítica Crónica de Células B/diagnóstico , Factores de Transcripción SOXC/genética , Anciano , Anciano de 80 o más Años , Ciclina D1/metabolismo , Femenino , Centro Germinal/patología , Humanos , Hibridación Fluorescente in Situ , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Factores de Transcripción SOXC/metabolismo , Translocación GenéticaRESUMEN
The normal counterparts of mantle cell lymphoma (MCL) are naive, quiescent B cells that have not been processed through the germinal center (GC). For this reason, although lymphomas arising from GC or post-GC B cells often exhibit plasmacytic differentiation, MCL rarely presents with plasmacytic features. Seven cases of MCL with a monotypic plasma cell (PC) population were collected from 6 centers and were studied by immunohistochemistry, fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms analysis, capillary gel electrophoresis, and restriction fragment length polymorphism of immunoglobulin heavy chain analysis of microdissections of each of the MCL and PC populations to assess their clonal relationship. The clinical presentation was rather unusual compared with typical MCL, with 2 cases arising from the extranodal soft tissues of the head. All MCL cases were morphologically and immunohistochemically typical, bearing the t(11;14)(q13;q32). In all cases, the PC population was clonal. In 5 of the 7 cases, the MCL and PC clones showed identical restriction fragments, indicating a common clonal origin of the neoplastic population. The 2 cases with clonal diversity denoted the coexistence of 2 different tumors in a composite lymphoma/PC neoplasm. Our findings suggest that MCL can present with a PC component that is often clonally related to the lymphoma, representing a rare but unique biological variant of this tumor.
Asunto(s)
Cromosomas Humanos Par 11 , Cromosomas Humanos Par 14 , Linfoma de Células del Manto/genética , Células Plasmáticas/patología , Translocación Genética/genética , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Células Clonales , ADN de Neoplasias/análisis , Femenino , Humanos , Técnicas para Inmunoenzimas , Cadenas Pesadas de Inmunoglobulina/genética , Inmunofenotipificación , Hibridación Fluorescente in Situ , Tejido Linfoide/metabolismo , Tejido Linfoide/patología , Linfoma de Células del Manto/metabolismo , Linfoma de Células del Manto/patología , Masculino , Microdisección , Persona de Mediana Edad , Células Plasmáticas/metabolismo , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
Follicular lymphomas with plasmacytic differentiation were described more than two decades ago. However, the possibility that some of these reported cases are marginal zone lymphomas or composite lymphomas must be considered. In addition, it is also uncertain whether follicular lymphomas with plasmacytic differentiation have any unique cytogenetic or other features. Therefore, fluorescence immunophenotypic and interphase cytogenetic analysis of 14 well-characterized follicular lymphomas with plasmacytic differentiation was performed using a CD138 antibody to identify the plasma cells and with BCL2, BCL6, IGH@ and MALT1 break-apart probes and a chromosome 12 centromeric probe. CD10 was expressed in 12/14 cases, BCL6 in 12/12 cases and BCL2 in 12/14 cases. At least one cytogenetic abnormality was identified in 12/14 cases. The same abnormality was present in both the plasmacytic (CD138+) and non-plasmacytic (CD138-) component in all 10 evaluable cases. BCL2 rearrangements were present in seven cases (5 IGH@ rearranged, 1 IGH@-not rearranged, 1 IGH@-not evaluable), BCL6 rearrangement in two (1 also with BCL2/IGH@ rearrangement), +12 in 1, +MALT1 without +18 in 1, IGH@ rearrangement without other abnormalities in 1 and IGH@ rearranged or partially deleted in 1 case. No cases showed +BCL6 (3q27) or a MALT1 rearrangement. All six cases with an isolated BCL2 rearrangement had predominantly interfollicular plasmacytic cells whereas, 6/7 cases without the translocation had concentrations of intrafollicular or perifollicular plasmacytic cells (P<0.005), as did the case with BCL2 and BCL6 translocations. These results support the existence of bona fide follicular lymphomas with plasmacytic differentiation and support the clonal relationship of the neoplastic lymphoid and plasma cells in at least most of these cases. The differential distribution of the plasma cells, specifically in relation to the presence or absence of an isolated BCL2 rearrangement suggests that the latter cases may be distinctive, sharing some features with marginal zone lymphomas.
Asunto(s)
Linfoma Folicular/genética , Linfoma Folicular/patología , Células Plasmáticas/patología , Adulto , Anciano , Anciano de 80 o más Años , Caspasas/biosíntesis , Caspasas/genética , Diferenciación Celular , Proteínas de Unión al ADN/biosíntesis , Proteínas de Unión al ADN/genética , Femenino , Reordenamiento Génico , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Inmunohistoquímica , Inmunofenotipificación , Hibridación Fluorescente in Situ , Linfoma Folicular/metabolismo , Masculino , Persona de Mediana Edad , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Neprilisina/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-6RESUMEN
BACKGROUND: Identification of disseminated nontuberculous Mycobacterium infection is a challenge, especially when it occurs in patients without a known cause of immunosuppression. Acid-fast organisms in the pleural fluid are rare and easily missed, especially when they occur in patients without a clinical suspicion of infection. The classical cytologic picture of tuberculous pleural fluid with lymphocytosis and paucity of mesothelial cells is not seen. CASE: A 57-year-old man presented with chronic neutrophilia of unknown etiology together with chest pain and bilateral pleural effusions. Pleural fluid cytology revealed organisms seen in the cytoplasm of numerous macrophages and neutrophils, creating a "negative image" on Diff-Quik smears. Acid-fast stains demonstrated intracellular acid-fast bacilli consistent with mycobacteria. Microbiologic studies with DNA probe technology resulted in identification of the mycobacterial organism as Mycobacterium kansasii. CONCLUSION: Nontuberculous Mycobacterium should be included in the differential diagnosis in patients with inflammatory, exudative pleural effusions.
Asunto(s)
Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Mycobacterium kansasii/aislamiento & purificación , Pleura/microbiología , Granuloma/patología , Humanos , Ganglios Linfáticos/patología , Macrófagos/microbiología , Masculino , Persona de Mediana Edad , Mycobacterium kansasii/citología , Neutrófilos/microbiologíaRESUMEN
Atypical adenomatous hyperplasia (AAH) is considered to be a precursor lesion of the lung adenocarcinoma. Several genetic abnormalities have been reported in AAH associated with adenocarcinoma, but little is known about AAH associated with benign lung lesions. To address this we compared the molecular characteristics of AAH present in benign conditions to those coexisting with carcinoma. Seven cases of AAH from resected non-neoplastic lungs (AAH-B) and 12 cases from lungs resected for primary lung carcinoma (AAH-M) were analyzed for loss of heterozygosity (LOH) using 21 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes on chromosomes 3p, 5q, 7p, 9p, 10q, and 17p. Direct DNA sequencing for K-ras mutation was also performed. There was a broad range of LOH in both groups. No LOH was identified in 3 cases (25%) of AAH-M, but all cases of AAH-B showed LOH (P=0.26). Six cases (50%) of AAH-M and 3 cases (43%) of AAH-B showed loss at 1 marker (P=0.99). LOH at 2 or more markers was identified in 3 (25%) cases of AAH-M and 4 (57%) cases of AAH-B (P=0.32). LOH was most frequently detected on chromosomes 3p and 10q in both groups. The difference in overall fractional allelic loss between the 2 groups did not reach statistical significance. K-ras mutations were not identified in either group. Our results showed a significant overlap in LOH patterns between AAH with or without coexistent lung malignancy. Therefore, AAH may represent a smoking induced low-grade neoplastic lesion that may be a precursor lesion of only a subset of invasive lung adenocarcinoma.