Small Nucleoli Research Articles

Piwi mutant germ cells transmit a form of heritable stress that promotes longevity

AbstractThe C. elegans Argonaute protein PRG‐1/Piwi and associated piRNAs protect metazoan genomes by silencing transposons and other types of foreign DNA. As prg‐1 mutants are propagated, their fertility deteriorates prior to the onset of a reproductive arrest phenotype that resembles a starvation‐induced stress response. We found that late‐generation prg‐1 mutants with substantially reduced fertility were long‐lived, whereas early‐ or mid‐generation prg‐1 mutants had normal lifespans. Loss of the stress response transcription factor DAF‐16 caused mid‐ or late‐generation prg‐1 mutants to live very short lives, whereas overexpression of DAF‐16 enabled both mid‐ and late‐generation prg‐1 mutants to live long. Cytoplasmic P‐bodies that respond to stress increased in long‐lived late‐generation prg‐1 mutants and were transmitted to F1 but not F2 cross‐progeny. Moreover, moderate levels of heritable stress shorten late‐generation prg‐1 mutant longevity when DAF‐16 or P bodies are deficient. Together, these results suggest that the longevity of late‐generation prg‐1 mutants is a hormetic stress response. However, dauer larvae that occur in response to stress were not observed in late‐generation prg‐1 mutants. Small germ cell nucleoli that depended on germline DAF‐16 were present in late‐generation prg‐1 mutants but were not necessary for their longevity. We propose that prg‐1 mutant germ cells transmit a form of heritable stress, high levels of which promote longevity and strongly reduce fertility. The heritable stress transmitted by prg‐1/Piwi mutant germ cells may be generally relevant to epigenetic inheritance of longevity.

CD5+ Large B cell lymphoma with IRF4 rearrangement: case report and review of the literature

Abstract Introduction/Objective Large B cell lymphoma with IRF4 rearrangement was introduced as a diagnosis by WHO in 2017. It is a rare entity that affects Waldeyer’s ring in mostly males, children and young adults. The lesional immunophenotype may be positive for CD10. FISH is positive for IRF4 rearrangement on chromosome 6p25.Among reported cases in the English literature only 6 cases have reported specifically CD5 being negative. We present review of the literature during years 2020-2024, and a case of large B cell lymphoma with IRF4 rearrangement, specifically positive for CD5. Methods/Case Report The patient is a 5 years old male, since 2017 suffering from recurring ear infections with approximately 4-5 episodes of otitis media during every 6 months. In 2019 the patient’s mother reported snoring, constant sore throat, bad breath for 2 years. On physical examination the left tonsil appeared enlarged; exudative tonsillitis was present. Later on, an asymmetric, firm mass in the location of the left tonsil with induration of the left palate was identified. CT scan showed mild asymmetric soft tissue thickening of the left aspect of the soft palate and left palatine tonsil. Mildly prominent left-sided levels IIa and IIb lymph nodes, measuring up to 1 cm were identified. H&E sections revealed an expansile proliferation of neoplastic cells, large with void to indented nuclei, vesicular chromatin, small nucleoli, visible cytoplasms. Frequent mitoses, apoptosis and individual cell necrosis were seen. Immunohistochemistry revealed CD20+ B cell neoplasm with high expression for MUM1 and high proliferation rate along with strong CD5+ and CD10-. By multicolor flow cytometric studies, an abnormal B cell population was found (40%) with increased forward scatter along with expression for CD5, CD19, CD20, CD22, CD45, CD79a (cytoplasmic), FMC7, (dim) lambda-restriction. Fluorescence In Situ Hybridization Study revealed IRF4 (DUSP22) rearrangement on chromosome 6p25. Results (if a Case Study enter NA) NA Conclusion We analyzed 24 cases reported in the English literature. The mean age of the patients is 7 years old. The majority are males (14/24 = 58%).The most common location is tonsil/ neck mass (15/24 = 62%).CD5 was negative in 6/24 cases.

Sebaceous gland epithelioma with potential malignancy in a dog

Sebaceous gland tumors consist of neoplastic proliferations of sebaceous gland cells located around hair follicles in the dermis. These tumors are subclassified as sebaceous epithelioma, sebaceous adenoma, sebaceous adenocarcinoma and nodular hyperplasia. In this case report, a nodular growth in the sacral region of an eight-year-old male Belgian Malinois dog was presented. Macroscopically, the nodular mass had a slightly soft consistency, grayish-white, and dark red-black appearance. The mass was measured in the dimension of 2x1x1 cm. Histopathologically, the tumor was observed to have a multilobular structure shaped by neoplastic cell islands. The tumor consisted mainly of eosinophilic cells with small cytoplasm resembling epithelial basaloid cells and to a lesser extent differentiated sebocytes. The parenchyma of the tumor consisted of irregular islets containing a small number of mature sebocytes. Their nuclei are oval with one to three small nucleoli. Immunohistochemically, tumor cells for Ki67 antibody showed strongly positive immunoreactivity. Based on the histopathological and immunohistochemical features, the tumor was diagnosed as sebaceous epithelioma having, a potential malignancy. Since no case of sebaceous epithelioma with malignant potential has been reported in our country, we aimed to present the case with histopathological and immunohistochemical features.

Myoepithelioma-Like Tumor of the Vulvar Region: A Clinicopathologic Study of Four Cases.

Myoepithelioma-like tumors of the vulvar region (MELTVR) are solid tumors found in the vulva of adult women. They have a similar histopathology to myoepithelioma but differ in immunohistochemical phenotype and genetic changes. In this study, we report four examples of MELTVR, occurred in the external genitalia and mons pubis of adult women aged 32 to 39 years. The tumors presented as subcutaneous masses without obvious tenderness. The tumors were composed of a mixture of myxoid and nonmyxoid components, and myxoid areas accounted for 5% to 80% of the tumor volume. The tumor cells were spindle-shaped or epithelioid, with abundant cytoplasm, vesicular nuclei, and small nucleoli. The nuclear atypia was mild to moderate, with 0 to 10 mitotic figures per 10 high-power fields. Immunohistochemically, all four tumors showed consistent positivity for EMA, calponin and ER; three tumors exhibited PR expression. All tumors were negative for S100 protein and SMA. AE1/AE3 expression was absent in all except one tumor, which showed rare positivity. SMARCB1/INI1 expression was deficient in all tumors. EWSR1 and FUS rearrangements were absent. All tumors were treated through surgery. All patients were alive without recurrence on most recent follow-up. Together, this overview of four additional tumors of MELTVR offers further insight into this rare and poorly understood disease.

Cytomorphological Features as a Subtyping Tool of Non-Small-Cell Lung Cancer in Brushing Bronchoscopic Samples.

Nowadays, the separation of adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs) is crucial given that there are new specific targeted therapies. So, the aim of this study was to examine the differences in cytomorphological features between ADC and SCC in bronchoscopic brush samples. The retrospective study was conducted over a 3-year period at Western Balkan University Hospital. All brushing samples were analysed. According to the histopathological report, patients were classified into ADC and SCC groups. The cytomorphological features analysed in 95 samples were presence of necrosis, cell distribution, nuclear atypia, size of nuclei, and visibility of nucleoli. Statistical analysis was performed in JASP, and P values <0.05 were considered significant. The necrotic background was more frequent in SCC samples. Small clusters sized ≤200 µm were found in 17.95% of samples from the SCC group and 53.57% in the ADC group. Large clusters sized >400 µm were found in 43.59% in the SCC group, while in the ADC group, it was found in 5.36%. There were no differences in nuclear atypia between groups. Nuclei that were >5x lymphocyte size were found more often in samples from ADC than in the SCC group (37.50 vs 10.25%). In 89.75% of samples from the SCC group, nuclei were ≤5x lymphocyte sizes, while in the ADC group, the percentage was 63.5%. Nucleoli were more often visible in samples from the ADC group compared to the SCC group (92.86% vs 64.10%, P < 0,05). Small clusters, large nuclei, and visible nucleoli were more frequent in the ADC group (P < 0.05), while large clusters, small nuclei, and invisible nucleoli were more frequent in the SCC group (P < 0.05).

Ewing Sarcoma of Kidney: A Rare Entity

AbstractPrimary renal origin of Ewing sarcoma/PNET (primitive neuroectodermal tumor) is a rare entity in the adult population and has an aggressive outcome. The entity was first coined by Arthur Purdy stout in 1918 and recognized under family of small round cell tumor. Radiologically it is difficult to distinguish from primary clear cell carcinoma of kidney from Ewing/PNET. Diagnosis of this requires histopathology, immunohistochemistry (IHC), and cytogenetics studies.A 40-year-old female presented with hematuria and radiology found a mass lower pole of left kidney with extension into renal hilum. Nephrectomy was done for the case and the histopathology diagnosis of small round cell tumor of left kidney was given. Followed by IHC, diagnosis of malignant round cell tumor was suggestive of Ewing sarcoma.Microscopy showed cells with small, round, hyperchromatic nuclei, scant cytoplasm, and inconspicuous nucleoli. Increased mitosis was noted (15/10 high power field). Multiple foci of pseudorosettes, areas of hemorrhage, and necrosis lymphovascular emboli were seen.IHC done outside showed NKX 2-2, synaptophysin positivity, CD99 diffuse membranous positivity, cytokeratin perinuclear dot like positivity, and negative for CD20, CD3, desmin, CD34, S100, and Pax8. Impression of malignant round cell tumor was suggestive of Ewing sarcoma.Ewing sarcoma is one of the rare yet highly aggressive tumors. This should be kept as differential diagnosis in young adults with renal mass, as on radiologically it cannot be differentiated from renal cell carcinoma. Diagnosis of Ewing sarcoma is done using histopathology, IHC, and cytogenetic study. Early diagnosis helps in initiation of surgery, chemotherapy, and radiotherapy and helps in increasing the survival rate.

Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma with significant granuloma: case report and literature review

BackgroundEpstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma (EBV+IFDCS) is a rare disease characterized by mild clinical symptoms and non-specific imaging findings. The diagnosis of the disease depends on pathological diagnosis. However, EBV+IFDCS has a very broad spectrum of histological morphology and immune phenotypes, and its histopathological features have not been fully described by pathologists.Case presentationA 59-year-old female, with no significant discomfort, was found to have a splenic mass during a routine physical examination. Microscopic examination at low magnification revealed numerous epithelioid granulomas, amidst which a substantial inflammatory response was observed. Interspersed among the dense inflammatory cells were spindle or oval-shaped cells, distributed sporadically with indistinct boundaries. Under high magnification, these spindle cells had subtle features: smooth and clear nuclear membranes, inconspicuous small nucleoli, and infrequent mitotic figures. Immunophenotypically, the spindle cells expressed CD21 and CD23, and Epstein-Barr encoding region (EBER) in situ hybridization yielded positive results. The inflammatory milieu predominantly consisted of T cells, with a minority of plasma cells expressing IgG4. The confluence of morphological and immunohistochemical findings led to the final pathological diagnosis of EBV+IFDCS in this case.ConclusionsThe presentation of EBV+IFDCS with pronounced granulomatous changes is rare. This morphological variant poses a high risk of misdiagnosis, frequently leading to confusion with other granulomatous diseases. Accurate diagnosis necessitates a comprehensive analysis, integrating immunohistochemistry and in situ hybridization. The case presented here is instrumental in raising awareness and understanding of EBV+IFDCS, with the goal of reducing misdiagnoses and unrecognized cases.

Subcutaneous Panniculitis-like T-cell Lymphoma: A Case Report of A Solved Conundrum

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma which often be very complexed to be diagnosed. Here we reported a case of a 38-year-old lady with wax and wane course of left facial swelling associated with prolonged pyrexia of unknown origin, lethargy and prominent weight loss. Multiple investigations were conducted to reach to the conclusive diagnosis. Histopathological showed infiltration of neoplastic lymphoid cells within the adipocyte clusters with hyperchromatic nuclei, small nucleoli and scant cytoplasm. Immunohistochemical analysis were immunoreactive to CD3, CD8 &amp; TIA and negative to CD20, CD4 &amp; CD56. Based on clinical findings, histopathology report and immunohistochemical analysis, the patient diagnosed with SPTCL. Hence, any suspicious maxillofacial swelling without obvious sign of infection and trauma shall be investigated until a final diagnosis is reached.

LncRNA SNHG8 regulates the migration and angiogenesis of pHUVECs induced by high glucose via the TRPM7/ERK1/2 signaling axis

This study aimed to evaluate the regulatory effect and molecular mechanism of long noncoding RNA small nucleolus RNA host gene 8 (LncRNA SNHG8) in the migration and angiogenesis of primary human umbilical vein endothelial cells (pHUVECs) under high-glucose (HG) conditions. The HG-induced endothelial injury model was established in vitro.The cell model of silencing SNHG8, overexpressing SNHG8, and silencing TRPM7 was established by transfecting SNHG8-siRNA, SNHG8 plasmid and TRPM7-siRNA into cells with liposomes.The SNHG8 level was determined through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression levels of transient receptor potential melastatin 7 (TRPM7), endothelial nitric oxide synthase (eNOS), p-eNOS, extracellular signal-regulated kinase 1/2(ERK1/2), and p-ERK1/2 were assessed through western blot. Nitric oxide (NO) levels were measured with DAF-FM. pHUVEC migration was examined through wound healing and Transwell assay, and pHUVEC angiogenesis was observed through a tube formation assay. Results showed that HG promoted the expression of lncRNA SNHG8 and TRPM7 and decreased the ratio of p-eNOS/eNOS and p-ERK1/2/ERK1/2 in pHUVECs . NO production, migration , and angiogenesis were inhibited in pHUVECs under HG conditions. Silencing lncRNA SNHG8 and TRPM7 could significantly reverse the HG-induced decrease in eNOS activation, NO production , migration, and angiogenesis . SNHG8 and U0126 (ERK pathway inhibitor) overexpression enhanced the HG effects, whereas using U0126 did not affect the TRPM7 expression. In conclusion, lncRNA SNHG8 participates in HG-induced endothelial cell injury and likely regulates NO production, migration, and angiogenesis of pHUVECs via the TRPM7/ERK1/2 signaling axis.

Synovial Sarcoma of the Descending Colon: Report of a Rare Case and Review of the Literature

Abstract Introduction/Objective Synovial Sarcoma is a mesenchymal malignancy that occurs primarily in the deep soft tissue near large joints of the extremities in young adults. Synovial sarcoma of the gastrointestinal tract is extremely rare. There is not enough literature to establish a consensus on management and treatment for colorectal synovial sarcoma. Methods/Case Report An 85-year-old male preresented with a positive cologuard test and the colonoscopy revealed a 12 mm polyp in the descending colon. Polypectomy was preformed. Histological examination exhibits spindle cell proliferation with fascicular growth pattern and with small nucleoli. There are collagen deposition, variable size of thick wall vessels and mixed inflammatory cells including lymphocytes, eosinophils and neutrophils in the background. Mitosis are identified. Immunohistochemical stains show tumor cells are negative for CD34, S100, DOG1, CD117, STAT6, Bcl-2, Desmin, and AE1/AE3, and focal positive for EMA, SMA and ALK. Immunohistochemical stain for SS18-SSX fusion protein is positive. Archer fusionplex targeted RNA sequencing (M23-1377) showed SS18:SSX2 fusion. A structural genomic alteration between the SS18 and SSX2 genes is detected [t(18;X)(q12.1;p11.22)]. These findings confirmed the diagnosis of synovial sarcoma. Results (if a Case Study enter NA) NA Conclusion Here we report a rare case of descending colon primary synovial sarcoma. Synovial sarcoma is generally considered as an aggressive and high-grade lesion with metastatic potential and its management is different from other colorectal neoplasms. This case report emphasies a wide differential diagnosis for colorectal lesions and prompt diagnosis and early management is important for better patient outcome.

Clinicopathological features of olfactory carcinoma

Objective: To investigate the clinicopathological features and differential diagnosis of olfactory carcinoma (OC). Methods: Twenty-one cases of sinonasal tumors, including those initially diagnosed as olfactory neuroblastoma (ONB) and those with uncertain diagnosis, were collected from the Department of Pathology, the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from January 2016 to August 2022, among which 3 cases were reclassified as OC. The clinicopathological features were investigated, and the remaining 18 cases were used as control. Results: Of the three OC patients, 2 were male and 1 was female, with an average age of 57 years ranging from 35 to 74 years. Microscopically, the tumor cells were arranged in solid, nested or lobulated patterns with occasional palisading around the solid nests. The stroma was highly vascular with focal neurofibrillary areas. There were prominent rosettes or pseudorosettes formation. The tumor cells were mainly ovoid to spindly with scant to moderate amount of cytoplasm, one or several small nucleoli, and fine chromatin content. Brisk mitotic figures were seen. In all 3 cases of OC, there were scanty atypical glands and some were ciliated. Immunohistochemically, at least one epithelial marker and neuroendocrine marker were diffusely expressed in the tumor. Some of the tumor cells were positive for p40 and p63, and the sustentacular cells showed the expression of S-100 protein. All cases tested were negative for NUT, CD99 and desmin, with intact expression of SMARCA4 (BRG1) and SMARCB1 (INI-1). Ki-67 proliferation index varied from 20% to 80%. Follow-up after 16-18 months showed no mortality with tumor recurrence from 1 patient after 16 months. Conclusion: OC is a rare sinonasal tumor with neuroepithelial differentiation, its histomorphology is diverse, and the combination of immunohistochemical markers is essential for appropriate diagnosis.

Postnatal Development of the Amygdala of Rat Offspring after Prenatal Exposure to Valproic Acid: A Histological and Morphometric Study

Abstract Background The amygdala has a major role in emotion regulation, social behavior development and reward learning. Being subject to several factors makes it vulnerable to numerous neurodevelopmental disorders. Aim of the Work The aim of the current work was to study the structural and morphometric changes of the amygdala of rat's offspring following maternal exposure to valproic acid during pregnancy and to compare it with the control. Material and methods 20 adult female and 10 adult male Sprague dawley albino rats weighing 150-200 g body weight were used in the current study. After induction of pregnancy, pregnant rats were divided into two groups 6 in each group; control group (I) and valproic acid treated group (II). Pregnant rats received one ml of saline in group (I) or 500 mg/kg BW valproic acid dissolved in one ml saline in group (II) by oral gavage on day 11-13 of pregnancy. Pregnant rats were observed till end of pregnancy and four male newborn rats were sacrificed at each time point of the experiment from the two groups (week1, 2, &amp;3). Brains were extracted and processed for paraffin blocks and sectioned then stained with H&amp;E, cresyl violet stains and immunohistochemically stained for GFAP antibody. Image analysis &amp;morphometry were performed on stained sections for; number of neurons, number of oligodendrocytes, surface area of basal nucleus of amygdala and density of GFAP staining. Results On examination of H&amp;E-stained sections of control groups during the first three weeks postnatally, the amygdala contained mainly three types of cells: pyramidal cells, oligodendrocytes, and astrocytes. Pyramidal cells had basophilic cytoplasm with large rounded open face nuclei and prominent nucleoli. Some pyramidal cells showed apical dendrites. The oligodendrocytes were seen to have rounded nuclei with condensed chromatin surrounded by thin cytoplasmic ring. Astrocytes possessed nuclei with pale vesicular chromatin pattern less dense than that of oligodendrocytes and showed relatively small indistinct nucleoli. Morphometric studies using image analysis had recorded statistically non-significant changes in the number of neurons during development, however concerning oligodendrocytes there was a statistically significant increase in their number in week 2 and 3 when compared to week 1. Using Nissl staining (cresyl violet) it demonstrated negative or very weak staining in the first week postnatally, the staining becomes more obvious in the next 2 weeks postnatally. GFAP immune stained sections of the amygdala of the 3 weeks revealed mild positive immune reaction. There was no statistically significant difference regarding density of staining across the three weeks. The surface area of the basal nucleus of amygdala of the control groups showed statistically significant increase during development across the three weeks. On examination of H&amp;E-stained sections of VPA treated groups during the first three weeks postnatally, numerous cells with pyknotic deeply basophilic stained nuclei were seen. Morphometric studies on the same groups using image analysis recorded statistically significant decrease in neurons and oligodendrocytes number when compared to control. On examination of the cresyl violet stained sections, there were numerous darkly stained degenerating cells that did not reveal the presence of Nissl granules denoting chromatolysis. On examining GFAP immune stained sections of the amygdala, week 2 and 3 postnatally showed strong positive immune reaction. The surface area of the basal nucleus of amygdala of VPA treated groups of weeks 1 showed a highly significant decrease when compared to week 1 of control groups, however the surface area of the amygdala of week 2 and 3 showed an increase more than the increase recorded in the control groups. The increase in the surface area was non-significant in week 2 but highly significant in week 3. Conclusion Results of the present experimental study demonstrated the developmental structural changes of the rat amygdala across the first three weeks of postnatal life. The study also explored the devastating effect of the prenatal exposure to VPA on the structure of the amygdala leading to neuronal death and gliosis particularly in the third week of age postnatally.

Malignant gastrointestinal neuroectodermal tumor: a clinicopathological analysis of three cases

Objective: To investigate the clinicopathological characteristics of malignant gastrointestinal neuroectodermal tumors (GNET), and to describe their clinical, histological, immunophenotypic, ultrastructural, and molecular features, diagnosis and differential diagnosis. Methods: Three cases of malignant GNET were collected at Xijing Hospital of the Fourth Military Medical University, from 2013 to 2022. All patients underwent surgical resection of the tumor. Histological, immunohistochemical (IHC), ultrastructural and molecular genetic analyses were performed, and the patients were followed up for six months, three years and five years. Results: There were two males and one female patients. The tumors were located in the ileum, descending colon, and rectum, respectively. Grossly, the tumors were solid, firm, and poorly circumscribed, measured in size from 2 to 4 cm in greatest dimension, and had a greyish-white cut surface. These tumors were histologically characterized by a sheet-like or nested population of oval to spindled cells or epithelioid cells with weakly eosinophilic or clear cytoplasm, small nucleoli and scattered mitoses. Electron microscopy showed neuroendocrine differentiation, and no evidence of melanogenesis. IHC staining showed that the tumor cells were diffusely positive for S-100 protein, SOX10, CD56, synaptophysin and vimentin. They were negative for melanocytic markers, HMB45 and Melan A. All three cases showed split EWSR1 signals consistent with a chromosomal translocation involving EWSR1. Next-generation sequencing in one case confirmed the presence of EWSR1-ATF1 fusion. These patients were followed up for 6 months, 3 years and 5 years, respectively, and all of them developed possible lung or liver metastases, and one of them died of multiple pulmonary metastases. Conclusion: Malignant GNET has distinctive morphological, IHC, and molecular genetic features and it should be differentiated from other malignancies of the gastrointestinal tract, especially clear cell sarcoma and melanoma.

Clinicopathologic and Immunophenotypic Classification of Invasive Lobular Carcinoma with Histiocytoid Features.

Histiocytoid lobular breast carcinoma is a rare subtype of invasive lobular carcinoma characterized by relatively bland, uniform nuclei, single small eosinophilic nucleolus, and ample granular cytoplasm. These cancers are typically triple negative, show frequent androgen receptor (AR) positivity, and are therefore theorized to represent a variant of apocrine differentiation in invasive lobular carcinoma. Anecdotal evidence suggests that these tumors have excellent outcomes, though some studies suggest a variable clinical outcome. Inclusion criteria included women with a histologic diagnosis of invasive lobular carcinoma with histiocytoid features, regardless of immunohistochemical profile, diagnosed at our institution between 2008 and 2021 with additional tissue still available for ancillary studies. We reviewed patients meeting these criteria and investigated hematoxylin and eosin-stained slides and a panel of immunohistochemical stains (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 [HER2], AR, endothelial growth factor receptor, and keratin 5/6), as well as outcomes including survival and metastatic disease. Overall, 12 eligible patients were identified. The classical immunophenotype (triple negative with AR positivity) was noted in 4 out of 12 tumors. The majority of the remaining tumors (7 out of 12) showed a luminal B immunohistochemical profile, while 1 out of 12 was HER2-enriched. No patients in the cohort died from disease-related causes and 2 out of 12 presented with distant metastatic disease during their disease course. Histiocytoid lobular breast carcinoma is a morphologic variant of lobular carcinoma with apocrine features that shows a variable immunohistochemical profile and variable clinical behavior. Further subclassification and stricter diagnostic criteria may be helpful in the distinction between truly indolent tumors and those with more aggressive clinical features.

Urine cytology in patients with gender confirmation surgery and hormone therapy: evaluation of urine cytology performance in an underserved patient population.

There is a practice gap and educational need regarding urine cytology (UC) performance in patients with history of gender confirmation surgery (GCS) and/or hormone therapy (HT). This potentially impacts diagnostic accuracy in this medically underserved population. We report a methodology that identifies relevant cases and evaluates the performance of UC in this cohort. Two institutional pathology archives from 2000 to 2021 were searched using relevant keywords to identify UC specimens from patients with GCS and/or HT for this retrospective study. For each specimen, patient demographics, relevant clinical history, and history of HT and/or GCS were noted. Each case was blindly reviewed by a cytopathologist according to The Paris System. A total of 32 UC specimens from 15 patients with history of GCS and/or HT were identified. There were 13 male to female and 2 female to male transgender patients. The original diagnosis was negative for high-grade urothelial carcinoma (NHGUC) in 24 of 32 (75%) and atypical urothelial cells (AUC) in 8 of 32 (25%) cases. The most common atypical features were irregular nuclear membranes and prominent small nucleoli in 7 of 8 (87.5%). Degenerative changes were present in 5 of 8 (62.5%). On re-review, with relevant clinical history, 100% of cases were re-classified as NHGUC. The original diagnosis of AUC in these cases likely reflects reactive changes post GCS and/or HT. This cohort may be at risk of AUC overdiagnosis, particularly if the pathologist is unaware of this clinical history. Pathologists need to recognize reactive cytomorphologic changes in these patients. Further multi-institutional studies are warranted to expand knowledge about UC performance in these patients.

Surgical resection of micronodular thymic carcinoma with lymphoid hyperplasia: a case report

BackgroundMicronodular thymic carcinoma with lymphoid hyperplasia is an extremely rare thymic tumor, exhibiting a variety of cell morphologies with mild to severe dysmorphism. Since few cases have been reported, the prognosis of this disease is unclear.Case presentationA 55-year-old woman was referred to our hospital with an anterior mediastinal tumor. She was incidentally detected with a tumor in a medical examination. We diagnosed the patient with thymic carcinoma or thymoma and performed surgery via median sternotomy. Histologically, tumor cells showed weakly acidic vesicles and bright nuclei, including small nucleoli. Most of the tumor cells were cluster of differentiation (CD)5-positive, CD3-negative, and terminal deoxynucleotidyl transferase (TdT)-negative.ConclusionsBased on these histological findings, the resected specimen was diagnosed as micronodular thymic carcinoma with lymphoid hyperplasia. The patient’s postoperative course was uneventful, and no signs of recurrence were observed at 5 years after the surgery.

MP50-12 CLINICOPATHOLOGIC ANALYSIS AND DIGITAL EVALUATION OF ORCHIECTOMY SPECIMENS IN PATIENTS WITH GENDER DYSPHORIA

You have accessJournal of UrologyCME1 Apr 2023MP50-12 CLINICOPATHOLOGIC ANALYSIS AND DIGITAL EVALUATION OF ORCHIECTOMY SPECIMENS IN PATIENTS WITH GENDER DYSPHORIA Ivan De La Riva, Ruoji Zhou, Alcino Gama, Bonnie Choy, Bogdan Isaila, Diana Bowen, Robert Brannigan, and Ximing Yang Ivan De La RivaIvan De La Riva More articles by this author , Ruoji ZhouRuoji Zhou More articles by this author , Alcino GamaAlcino Gama More articles by this author , Bonnie ChoyBonnie Choy More articles by this author , Bogdan IsailaBogdan Isaila More articles by this author , Diana BowenDiana Bowen More articles by this author , Robert BranniganRobert Brannigan More articles by this author , and Ximing YangXiming Yang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003298.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Gender-affirmation therapy for transgender individuals is an area of increasing importance in genitourinary pathology. These patients undergo various forms of hormonal replacement therapy (HRT) followed by bilateral orchiectomy. To date, there are very limited studies on the histological and biochemical alterations in these testes. METHODS: We conducted a retrospective search of the database for gender-affirming orchiectomies performed at our institution from 2018 to 2022. Clinical features, including age, length and types of hormonal treatment, and pathologic features, were reviewed and summarized. 19 cases were subjected to whole slide imaging scanning for digital analysis using the Leica system. Immunohistochemistry for OCT4 and CD117 was performed on selected cases. RESULTS: Atrophic changes and decreased spermatogenesis were found in all the gender-affirming orchiectomy specimens examined, with decreased mean tubule diameter (102.9 μm, 202 tubules examined) compared to the tubular size of germ cell neoplasia in situ (GCNIS) and normal testis (139.3 μm and 143.7 μm, 326 and 185 tubules examined, respectively). All cases showed significant maturation arrest, with 55 testes showing aspermatogenesis and the remaining 14 testes showing hypospermatogenesis. Various degrees of basement membrane thickening were observed in all testes, and 55.1% of the testes were found to have focal tubule hyalinization/obliteration. The number of Leydig cells was reduced, with marked cytoplasmic vacuolization and degenerative changes. In a subset of specimens, scattered germ cells displayed prominent nucleomegaly. Using digital analysis, the average nuclear size of these abnormal germ cells was 14.4 μm in diameter (35 cells counted), approaching or exceeding the size of the neoplastic nucleus in GCNIS (mean diameter=12.1 μm, 33 cells counted). However, the enlarged nuclei of these germ cells demonstrated a smooth nuclear membrane, small nucleoli, and fine granular and smudged chromatin, significantly different from the nuclei in GCNIS. Furthermore, immunohistochemistry staining of the germ cells with nucleomegaly in tested cases demonstrated negative staining for both OCT4 and CD117, militating again the possibility of GCNIS. CONCLUSIONS: All the testes from gender-affirming orchiectomies in our study exhibit significantly reduced spermatogenesis, including maturation arrest and atrophic changes. In addition, the presence of scattered germ cells with nucleomegaly in these specimens can mimic GCNIS. Source of Funding: NA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e689 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ivan De La Riva More articles by this author Ruoji Zhou More articles by this author Alcino Gama More articles by this author Bonnie Choy More articles by this author Bogdan Isaila More articles by this author Diana Bowen More articles by this author Robert Brannigan More articles by this author Ximing Yang More articles by this author Expand All Advertisement PDF downloadLoading ...

Bronchial cytology of pulmonary adenoid cystic carcinoma – A multi-institute series with emphasis on immunocytochemistry

BackgroundPulmonary adenoid cystic carcinoma (AdCC) is a central and superficial primary lung neoplasm, well-suited for sampling by bronchial cytology. This study aims to review the cytologic features of pulmonary AdCC on bronchial cytology, and to report an experience of applying immunocytochemistry on this rare entity. MethodsA multi-institute review of bronchial cytology specimens from histologically proven pulmonary AdCCs was performed. Published cases of bronchial cytology of pulmonary AdCC were reviewed. The cytologic features and immunocytochemical profile for pulmonary AdCC was summarized and compared with pertinent differentials. ResultsA total of 16 specimens from eight patients were retrieved. The initial cytologic diagnoses were negative (n = 7), atypia (n = 6), suspicious (n = 2) and AdCC (n = 1). Retrospective review showed eight bronchial cytology specimens (including five cases of atypia) with tumor cells present. The tumor cells displayed small basaloid nuclei with occasional small nucleoli, mild nuclear atypia, and scanty cytoplasm. Architectural patterns observed included clusters, tubules, solid sheets, three-dimensional balls, papillary-like fronds, and complex cribriform structures. Basement-membrane-like material, free or associated with tumor cells, were seen in all cases. Immunocytochemistry was performed in one specimen. MYB was positive. TTF-1, synaptophysin and chromogranin were negative. Epithelial and basal markers demonstrated a dual cell population. Literature review yielded 28 cases. Cytologic features described were similar except for cytoplasmic vacuolation in one case. ConclusionBasement membrane-like material is specific for AdCC. MYB positivity, TTF-1 and neuroendocrine marker negativity, support a diagnosis of AdCC. Other immunocytochemistry and cytologic features overlap significantly with adenocarcinoma and small cell carcinoma of lung.

Extraenteric Malignant Gastrointestinal Neuroectodermal Tumor—A Clinicopathologic and Molecular Genetic Study of 11 Cases

Malignant gastrointestinal neuroectodermal tumors (MGNETs), also known as “gastrointestinal clear cell sarcoma–like tumors”, are very rare, aggressive sarcomas characterized by enteric location, distinctive pathologic features, and EWSR1/FUS::ATF1/CREB1 fusions. Despite identical genetics, the clinicopathologic features of MGNET are otherwise quite different from those of clear cell sarcoma of soft parts. Only exceptional extraenteric MGNET (E-MGNET) has been reported. We report a series of 11 E-MGNETs, the largest to date. Cases diagnosed with MGNET and occurring in nonintestinal locations were retrieved. A clinical follow-up was obtained. The tumors occurred in 3 men and 8 women (range, 14-70 years of age; median, 33 years) and involved the soft tissues of the neck (3), shoulder (1), buttock (2), orbit (1), tongue/parapharyngeal space (1), urinary bladder (1), and falciform ligament/liver (1). Tumors showed morphologic features of enteric MGNET (small, relatively uniform, round to ovoid cells with round, regular nuclei containing small nucleoli growing in multinodular and vaguely lobular patterns, with solid, pseudoalveolar, and pseudopapillary architecture). Immunohistochemical results were S100 protein (11/11), SOX10 (11/11), synaptophysin (3/10), CD56 (7/9), CD117 (3/9), DOG1 (0/4), ALK (4/8), chromogranin A (0/10), HMB-45 (0/11), Melan-A (0/11), tyrosinase (0/4), and MiTF (0/11). Next-generation sequencing results were EWSR1::ATF1 (7 cases), EWSR1::CREB1 (3 cases), and EWSR1::PBX1 (1 case). The EWSR1::PBX1-positive tumor was similar to other cases, including osteoclast-like giant cells, and negative for myoepithelial markers. A clinical follow-up (range, 10-70 months; median, 34 months) showed 4 patients dead of disease (10.5, 12, 25, and 64 months after diagnosis), 1 patient alive with extensive metastases (43 months after diagnosis), 1 patient alive with persistent local disease (11 months after diagnosis), and 4 alive without disease (10, 47, 53, and 70 months after diagnosis). One case is too recent for the follow-up. The clinicopathologic and molecular genetic features of rare E-MGNET are essentially identical to those occurring in intestinal locations. Otherwise, typical E-MGNET may harbor EWSR1::PBX1, a finding previously unreported in this tumor type. As in enteric locations, the behavior of E-MGNET is aggressive, with metastases and/or death from disease in at least 50% of patients. E-MGNET should be distinguished from clear cell sarcoma of soft parts and other tumors with similar fusions. ALK expression appears to be a common feature of tumors harboring EWSR1/FUS::ATF1/CREB1 fusion but is unlikely to predict the therapeutic response to ALK inhibition. Future advances in our understanding of these unusual tumors will hopefully lead to improved nomenclature.

Oncocytic Papillary Cystadenoma, an Unusual Variant Presenting as a Laryngeal Ventricular Cyst.

Cystadenoma arising from the larynx is a rare benign minor salivary gland tumor that can show mucinous or papillary morphology. The epithelial lining of the salivary gland tumor can present with oncocytic features, which is attributed to an increased number of mitochondria. We present a rare case of oncocytic papillary cystadenoma (OPC) of the larynx which has a combination of these features. The WHO defines OPC tumors as entities which closely resemble Warthin tumor, but lack its classic lymphoid component. The immunohistochemical profile and molecular genetic features are largely unknown. We present an 84-year-old female, former smoker, who presented with progressive dysphonia, dysphagia, and shortness of breath. Laryngoscopy revealed a large, smooth mass originating from the ventricle of the right vocal fold. Subsequent biopsy demonstrated cyst wall fragments lined by a bilayer of large columnar to cuboidal oncocytic cells that had granular eosinophilic cytoplasm, round to oval nuclei with finely dispersed chromatin, and small but distinct nucleoli. The surrounding stroma was slightly fibrotic with scant lymphoid elements. No nuclear pleomorphism, increased mitosis, or necrosis was identified. In the larynx, benign salivary gland tumors are rare and less frequent than malignant neoplasms. Awareness of rare benign entities like OPC help ensure proper management and aid in avoiding unnecessary therapy.