RESUMO
We report 21 cases of trichogerminoma harbouring previously undescribed FOXK1::GRHL1/2 or GPS2::GRHL1/2/3 in-frame fusion transcripts. Microscopic examination of a preliminary set of five cases revealed well-delimitated tumours located in the dermis with frequent extension to the subcutaneous tissue. Tumours presented a massive and nodular architecture and consisted of a proliferation of basaloid cells. A biphasic pattern sometime resulting in tumour cell nests ('cell balls') was present. Immunohistochemistry demonstrated the expression of cytokeratins (CKs) 15, 17, and PHLDA1. In addition, numerous CK20-positive Merkel cells were detected. RNA sequencing (RNA-seq) revealed a FOXK1::GRHL1 chimeric transcript in three cases and a FOXK1::GRHL2 fusion in two cases. In a second series for validation (n = 88), FOXK1::GRHL1/2 fusion transcripts were detected by RT-qPCR or FISH in an additional 12 trichogerminomas and not in any other follicular tumour entities or basal cell carcinoma cases (n = 66). Additional RNA-seq analysis in trichogerminoma cases without detected FOXK1::GRHL1/2 rearrangements revealed GPS2::GRHL1 fusion transcripts in two cases, GPS2::GRHL2 in one case, and GPS2::GRHL3 fusion transcript in one case. Therefore, our study strongly suggests that GRHL1/2/3 gene rearrangements might represent the oncogenic driver in trichogerminoma, a subset of follicular tumours characterized by immature features and numerous Merkel cells. © 2022 The Pathological Society of Great Britain and Ireland.
Assuntos
Neoplasias Cutâneas , Fatores de Transcrição Forkhead/genética , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Reino UnidoRESUMO
Two cases of malaria related chronic splenomegaly, one with tropical splenic lymphoma with villous lymphocytes (TSLVL) and the other with hyperreactive malarial splenomegaly (HMS) were analyzed by cytology, histology, karyotyping, immunophenotyping, and polymerase chain reaction (PCR) for detection of bcl-2/JH and FR3/JH rearrangements on blood and bone marrow samples, at diagnosis and 12 months after malarial prophylaxis. The reported data suggest that the detection of FR3/JH rearrangement might contribute to the diagnosis of TSLVL in patients with malaria related chronic splenomegaly, for whom bcl-2/JH rearrangement may be a common molecular event.
Assuntos
Genes de Imunoglobulinas/genética , Linfoma/diagnóstico , Malária/complicações , Proteínas Proto-Oncogênicas c-bcl-2/genética , Esplenomegalia/genética , Esplenomegalia/parasitologia , Idoso , Linfócitos B , Doença Crônica , Feminino , Rearranjo Gênico , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Imunofenotipagem , Linfoma/genética , Linfoma/parasitologia , Masculino , Pessoa de Meia-Idade , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/parasitologiaRESUMO
Dieulafoy's ulcer is a particular form of gastric ulcer confined to a persistent caliber artery and may lead to severe hemorrhage. We report a case of fatal gastric bleeding in a woman with benign biclonal gammapathy. Autopsy found a typical Dieulafoy's ulcer centered by a persistent caliber artery which wall was thickened by AL-amyloid deposits. Amyloidosis involved the gastric wall, but also middle caliber arteries of the liver, the lung, the pancreas, the kidney and the myocardium. AL-amyloidosis is a rare and late complication of monoclonal gammapathy and may be asymptomatic. Pathogenesis of Dieulafoy's ulcer remains unclear. In our case, local ischemia may have facilitated gastric ulceration, and amyloid deposits may have contributed to arterial rupture.
Assuntos
Amiloidose/etiologia , Artérias/anormalidades , Hemorragia Gastrointestinal/etiologia , Paraproteinemias/complicações , Gastropatias/etiologia , Úlcera Gástrica/complicações , Idoso , Amiloidose/patologia , Artérias/patologia , Evolução Fatal , Feminino , Hematemese/etiologia , Humanos , Isquemia/complicações , Estômago/irrigação sanguínea , Gastropatias/patologia , Úlcera Gástrica/patologiaRESUMO
Myeloid sarcoma (MS) of the prostate is very uncommon with only 17 reported cases in the literature. Here, a singular case of a MS of the prostate discovered through investigations for urinary retention and revealing an acute leukaemia classified as an acute myeloid leukaemia (AML) with inversion 16 (inv16) according to the World Health Organization (WHO) classification (AML-M4 with inv16 in the French-American-British (FAB) classification) in a 65-year-old man is presented. None of the previously reported and reviewed cases of prostatic MS were of AML-M4 type. Moreover, a translocation t(3;7) was identified in our case. Such a translocation was recently described in some acute myeloid processes. MS treatment consists of combining surgical intervention and chemotherapy. Radiation therapy could be beneficial for the localised disease of the prostate. Allogenic haematopoietic stem cell transplantation is also a promising therapy for MS.
RESUMO
Adenomyoma and adenomyomatous hyperplasia of the Vaterian system are consistently benign lesions. Clinically, adenomyoma mimics frequently ampullary adenoma or carcinoma, and biopsy analysis is often difficult. The histogenesis of ampullary adenomyoma and adenomyomatous hyperplasia is still subject to debate. We present a retrospective study of clinicopathological features of 13 cases of surgically resected ampullary adenomyoma. The age of our patients was between 38 and 78 years (mean: 63 y). The preoperative diagnosis was ampullary tumor or tumor of the head of the pancreas. On macroscopy, a white, firm lesion of the ampullary wall was observed; its size ranged between 10 and 30 mm. Histologically the lesion consisted of multiple glandular structures surrounded by a fibroblastic/myofibroblastic proliferation, resulting in a "pseudo-hypertrophy" of the Vaterian system. The immunophenotype of the epithelial component was cytokeratin 7+/cytokeratin 20-, similar to that of the normal biliary and pancreatic duct system. The epithelial cells exhibited low proliferative activity. The hyperplastic myofibroblastic cells expressed smooth muscle actin. A complete pancreatic heterotopy contiguous with the adenomyoma was noted in three cases. Adenomyoma and adenomyomatous hyperplasia of the Vaterian system are benign lesions frequently treated by extensive surgery because of long-term biliary obstruction. The clinicopathological characteristics suggest either a reactive and/or a malformative, nonneoplastic nature for this lesion, which could, in some cases, develop from heterotopic pancreas. The immunophenotype of epithelial cells may be a useful tool for differentiating it from ampullary adenoma on biopsy specimens.
Assuntos
Adenomioma/patologia , Ampola Hepatopancreática/patologia , Neoplasias do Ducto Colédoco/patologia , Hiperplasia/patologia , Adenomioma/metabolismo , Adenomioma/cirurgia , Adulto , Idoso , Ampola Hepatopancreática/metabolismo , Ampola Hepatopancreática/cirurgia , Biomarcadores Tumorais/metabolismo , Neoplasias do Ducto Colédoco/metabolismo , Neoplasias do Ducto Colédoco/cirurgia , Feminino , Humanos , Hiperplasia/metabolismo , Hiperplasia/cirurgia , Imuno-Histoquímica , Proteínas de Filamentos Intermediários/metabolismo , Queratina-20 , Queratina-7 , Queratinas/metabolismo , Masculino , Pessoa de Meia-Idade , Pancreaticoduodenectomia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We tested the ability of human cells from different hematopoietic tissues to generate graft versus host disease-like syndrome (GVHD) in sublethally irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Tissue sources of human hematopoietic cells were: (1) bone marrow (BM), (2) nonmobilized peripheral blood (PB), (3) mobilized peripheral blood stem-progenitor cells (PBSC), and (4) cord blood (CB). To avoid interindividual donor variation, part of this study was done using BM, PB, and PBSC donated by a single healthy adult volunteer. A total of 179 NOD/SCID mice received graded human hematopoietic cell doses [5-500 x 10(6) mononuclear cells (MNC), containing 2-325 x 10(6) CD3(+) T cells, per mouse] from individual donors. Mice were observed for the development of GVHD and sacrificed 60 days after transplantation (earlier if ill). Mice were analyzed quantitatively by flow cytometry for human hematopoietic cell types and histologically, especially for human T lymphocytes infiltrating BM. No mouse transplanted with the tested doses of human CB or BM cells developed GVHD (experimentally defined as >10% human T lymphocytes infiltrating the mouse BM). For PB and PBSC, the frequencies of death, death with GVHD, and GVHD were directly related to the dose and source of human cells. Because PB cells contaminate harvested BM, the results from infused BM and PB were next combined for further analysis (BM/PB). The relative risks (hazard ratios estimated from the proportional hazards model) for death with GVHD, for each 10 human T cell dose increase, were 1.15 for BM/PB (p < 0.0001) and 1.47 for PBSC (p < 0.0001). In this in vivo xenogeneic model, the average T cell from human PBSC generated GVHD more potently than did the average T cell from human BM/PB, and the average CB T cell had a much lower GVHD potential. These results suggest that the potential for clinical GVHD from an HLA-disparate donor graft is likely to be quantitatively dependent both on the total number of T lymphocytes in the donor graft and the tissue source of the graft. Quantitative criteria for optimal T cell content of allogeneic donor hematopoietic grafts from different sources are discussed.
Assuntos
Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco/métodos , Animais , Células Sanguíneas/transplante , Transplante de Medula Óssea/métodos , Transplante de Medula Óssea/normas , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/normas , Humanos , Incidência , Contagem de Linfócitos , Camundongos , Camundongos SCID , Transplante de Células-Tronco de Sangue Periférico/métodos , Transplante de Células-Tronco de Sangue Periférico/normas , Risco , Transplante de Células-Tronco/normas , Taxa de Sobrevida , Linfócitos T , Transplante Heterólogo/métodos , Transplante Heterólogo/normasRESUMO
STUDY OBJECTIVE: To describe the histologic appearance of deep endometriosis infiltrating the uterosacral ligaments (USL). DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: One hundred forty-nine women with pain due to endometriosis. INTERVENTION: Resection of one or both USL. MEASUREMENTS AND MAIN RESULTS: One hundred seventy-two USL were examined by histology after unilateral resection in 126 patients (84.6%) and bilateral resection in 23 (15.4%). Two-thirds of women (122, 70.9%) had a classic appearance of endometriosis. Lesions of myoproliferative endometriosis with a histologic appearance of so-called adenomyotic nodules were observed in 25 (14.5%). Associated fibrosis was most frequent in patients with positive compared with negative histology (85, 69.7% vs 18, 36.0%). CONCLUSION: Anatomicopathologic lesions of deep endometriosis infiltrating the USL are heterogeneous. Adenomyotic nodules are not frequently observed.