Histopathological Features Research Articles

Cysts of the ligamentum flavum are often linked to ischemic conditions: A morphological study.

"Cysts of the ligamentum flavum (cysts-LF)" is the term for non-neoplastic cystic lesion involving LF. The aim of the present study was to elucidate the histopathological characteristics and pathogenesis of "cysts-LF". Herein, we defined cysts-LF as spinal cysts containing degenerative LF components. From archival cases, we investigated 18 symptomatic cysts-LF surgically removed from 18 patients (13 males and five females; median age 68.5 years [range, 42-86 years]). The elastic fibers of LF components in the wall were separated and/or torn, and cyst walls were accompanied by chondroid metaplasia (17 cases), myxoid changes (13 cases), ossification (11 cases), amyloid deposits (14 cases), hemosiderosis (six cases), granular/smudgy calcification (four cases), synovial cell linings (three cases), and severe inflammatory infiltrates (one case). These histologic features of our cysts-LF were shared by previously reported "cysts-LF." Fourteen cysts-LF demonstrated vascular stenosis/occlusion, and eight showed thick hyalinized vessels, suggesting local circulatory insufficiency. Eight cases (44%) exhibited lipomembranous fat necrosis, accompanied by hyalinized vascular changes (p = 0.003). Ischemic conditions were observed in nearly half of the present cysts-LF, and may be one of the main contributing factors for the formation of cysts-LF, via degeneration and cystic changes in the LF.

Comparative study of cemento-ossifying fibroma and focal cemento-osseous dysplasia in the jaw – 15 year retrospective inquiry and literature review

BackgroundCemento-ossifying fibroma (COF) and focal cemento-osseous dysplasia (FCOD) are benign neoplasms occurring in the mandible and maxilla; histologically, they both show normal bone replacement by a fibrous stroma containing variable amounts of calcified fragments resembling bone and cementum. FCOD is relatively common and requires observation; COF is rare and its growth over time can lead to deformity in the head and neck region. Surgical removal of COF at an early stage is critical to prevent recurrence and deformity. Therefore, distinguishing COF from FCOD is important for proper further management. Methods and MaterialsTo determine the parameters differentiating COF from FCOD, we retrospectively analyzed 15 COF cases and 27 FCOD cases reviewed between 2005 and 2020 at Temple University Hospital. Demographic, radiographic and histopathologic characteristics were compared by using Student’s t test for continuous variables and Chi-square test for categorical variables. ResultsIn the non-histopathologic spectrum, COF occurred at a younger age (average age-31yo versus FCOD 43 yo). FCOD showed female predilection compared with COF. No significant difference was observed regarding location and radiographic density. However, COF was significantly associated with radiographic cortical expansion. In the histopathologic spectrum, FCOD was more frequently associated with significant intralesional hemorrhage, increased vascularity, osteoblastic rimming of trabeculae, and ginger roots –like bone trabeculae. DiscussionWe demonstrated 7 clinical, radiographic, and pathologic parameters that can help differentiate COF from FCOD. Comprehensive assessment of the distinguishing characteristics is valuable for accurate diagnosis and treatment of these two entities, aiding in minimizing unnecessary procedures for FCOD and averting facial deformities caused by COF.

Clinicopathological phenotype and outcomes of NCAM-1+ membranous lupus nephritis.

No studies explored the long-term outcomes of neural cell adhesion molecule 1 (NCAM1) associated membranous lupus nephritis (MLN) patients. We performed immunohistochemical studies on kidney biopsy specimens against NCAM1 in consecutive MLN patients. The clinical and histopathological characteristics and outcomes of cases of NCAM1 associated MLN patients are described and compared with NCAM1 negative patients. In addition, we detected serum circulating anti-NCAM1 antibodies through western blotting and indirect immunofluorescence assays. Among 361 MLN cases, 18 (5.0%) were glomerular NCAM1-positive. NCAM1 positive MLN patients were older [35 years (IQR 27-43) versus 28 (22-37); P=0.050) and had lower systemic lupus erythematosus disease activity index [11 (IQR 8-12) versus 14 (10-18); P=0.007], serum creatinine [60 μmol/L (IQR 50-70) versus 70 (54-114); P=0.029], activity index [3 (IQR 2-6) versus 6 (3-9); P=0.045] at kidney biopsy compared with NCAM1 negative patients. The percentage of positive anti-Sjogren's syndrome related antigen A antibodies in NCAM1 positive patients was significantly greater (83.3% versus 58.2%; P=0.035) than in the NCAM1 negative patients. However, no evidence of neuropsychiatric disorders was found in these 18 patients. There were no significant differences in the treatment response and the risk of end stage renal diseases between NCAM1 positive and negative groups (P=0.668 and P=0.318, respectively). But the risk of death was much higher in the NCAM1 positive group than the NCAM1 negative group (27.8%vs. 8.1%, P=0.007). Moreover, the risk of death was also much higher in the NCAM1 positive group than the matched NCAM1 negative group (Log-rank P=0.013). Additionally, circulating anti-NCAM1 antibodies can be detected in 1/5 (20%) patients who had serum available. The prevalence of NCAM1 positivity was 5.0% in our cohort of MLN and the high mortality in these subgroup patients are needed to validate in future studies.

A Review of Myositis-Associated Interstitial Lung Disease.

There is a well-established relationship between different subsets of idiopathic inflammatory myopathies (IIMs, myositis) and interstitial lung disease (ILD), with lung complications sometimes presenting prior to myopathic manifestations. The subtypes of myositis include those that are strongly associated with ILD, such as polymyositis (PM) and dermatomyositis (DM). Research has shown that in certain patients, these can then be further divided into subtypes using myositis-specific antibodies (MSAs), which are specific for myositis, and myositis-associated antibodies (MAAs), which can be found in myositis in overlap syndromes with other connective tissue diseases (CTDs). Notably, certain MSAs and MAAs are associated with ILD in patients with myositis. The clinical presentations of ILD in patients with myositis can vary widely and can be insidious in onset and difficult to diagnose. As ILD can progress rapidly in some cases, it is essential that clinicians are able to identify and diagnose ILD in patients with myositis. For this reason, the aim of this review is to highlight the clinical features, diagnostic criteria, important histopathologic, laboratory, and radiographic features, and treatment modalities for those patients with myositis-associated ILD.

Pilomatrixoma of the Periorbital Region: A Retrospective Review.

Pilomatrixoma is a benign cutaneous adnexal tumor that differentiates toward hair follicle cells. It infrequently occurs in the periorbital region. In the periorbital area, it is often located in the upper eyelid and eyebrow region. Periorbital pilomatrixoma is often misdiagnosed clinically and is less common than other benign skin tumors. In this retrospective review, we evaluate the demographic, clinical, and histopathological data of patients with periorbital pilomatrixoma, treated from 2010 to 2023. A retrospective analysis of periorbital pilomatrixoma cases treated during a period of 13 years was performed. Deidentified data in relation to the age at surgical excision, gender, location, size, histopathological features, treatment, and recurrence were collected. All histological slides were reviewed by an attending histopathologist. A total of 77 cases of periorbital pilomatrixoma were diagnosed by histopathological examination and treated from 2010 to 2023. A slight female preponderance (56%) was noted, and the majority of cases (52%) were presented in the first 2 decades of life. The left periorbital region was involved in 45.5% of cases, and 54.5% in the right. The upper lid was the most affected site. Two cases of recurrence were reported. No malignant transformation was noted. Pilomatrixoma is an uncommon benign periorbital tumor, commonly misdiagnosed clinically. Ophthalmologists and surgeons should suspect pilomatrixoma in the periorbital region, especially in children or young adults. Complete surgical excision is curative, and recurrence is rare.

Case Report on Dedifferentiated Carcinoma of Endometrium and It’s Histopathological Characteristics

Case Report on Dedifferentiated Carcinoma of Endometrium and It’s Histopathological Characteristics

On the Boundary of Exploratory Genomics and Translation in Sequential Glioblastoma.

OMICS methods brought significant advancements to the understanding of tumor cell biology, which transformed the treatment and prognosis of several cancers. Clinical practice and outcomes, however, changed significantly less in the case of glioblastoma (GBM). In this study, we aimed to assess the utility of whole exome (WES) sequencing in the clinical setting. Ten pairs of formalin-fixed, paraffin-embedded (FFPE) GBM specimens were obtained at onset (GBM-P) and at recurrence (GBM-R). Histopathological and molecular features of all samples supported the diagnosis of GBM based on WHO CNS5. WES data were filtered, applying a strict and custom-made pipeline, and occurrence of oncogenic and likely oncogenic variants in GBM-P, GBM-R or both were identified by using the VarSeq program version 2.5.0 (Golden Helix, Inc.). Characteristics and recurrence of the variants were analyzed in our own cohort and were also compared to those available in the COSMIC database. The lists of oncogenic and likely oncogenic variants corresponded to those identified in other studies. The average number of these variants were 4 and 5 out of all detected 24 and 34 variants in GBM-P and GBM-R samples, respectively. On average, one shared oncogenic/likely oncogenic variant was found in the pairs. We assessed the identified variants' therapeutic significance, also taking into consideration the guidelines by the Association for Molecular Pathology (AMP). Our data support that a thorough WES analysis is suitable for identifying oncogenic and likely oncogenic variants in an individual clinical sample or a small cohort of FFPE glioma specimens, which concur with those of comprehensive research studies. Such analyses also allow us to monitor molecular dynamics of sequential GBM. In addition, careful evaluation of data according to the AMP guideline reveal that though therapeutic applicability of the variants is generally limited in the clinic, such information may be valuable in selected cases, and can support innovative preclinical and clinical trials.

Cross-species transmission and histopathological variation in specific-pathogen-free minipigs infected with different hepatitis E virus strains

Hepatitis E virus (HEV) is a major cause of viral hepatitis worldwide. Pigs are the natural host of HEV genotype 3 and the main reservoir of HEV. As the host range of HEV genotype 3 expands, the possibility that HEV from various species can be transmitted to humans via pigs is increasing. We investigated the potential cross-species transmission of HEV by infecting minipigs with swine HEV (swHEV), rabbit HEV (rbHEV), and human HEV (huHEV) and examining their histopathological characteristics and distribution in various organs. Fifteen specific-pathogen-free Yucatan minipigs were infected with swHEV, rbHEV, huHEV, or a mock control. In the present study, we analysed faecal shedding, viremia, and serological parameters over a seven-week period. Our results indicated that swHEV exhibited more robust shedding and viremia than non-swHEVs. Only swHEV affected the serological parameters, suggesting strain-specific differences. Histopathological examination revealed distinct patterns in the liver, pancreas, intestine, and lymphoid tissues after infection with each HEV strain. Notably, all three HEVs induced histopathological changes in the pancreas, supporting the association of HEVs with acute pancreatitis. Our results also identified skeletal muscle as a site of HEV antigen presence, suggesting a potential link to myositis. In conclusion, this study provides valuable insights into the infection dynamics of different HEV strains in minipigs, emphasizing the strain-specific variations in virological, serological, and histological parameters. The observed differences in infection kinetics and tissue tropism will contribute to our understanding of HEV pathogenesis and the potential for cross-species transmission.

Primary pulmonary enteric adenocarcinoma: A case report and review of literature

Primary pulmonary enteric adenocarcinoma (P-PEAC) is an unusual subtype of invasive lung adenocarcinoma. The significance of such tumor lies in its similar histopathological and immunohistochemical characteristics to colorectal adenocarcinoma. Therefore, a detailed investigation is crucial to establish a definitive diagnosis. This paper reports a case of a 51-year-old Saudi female, diagnosed with a rare variant of lung carcinoma, P-PEAC.

Morphomolecular Correlation and Clinicopathologic Analysis in Endometrial Carcinoma.

Research groups have identified 4 groups [polymerase epsilon (POLE) mutant, mismatch repair-deficient, p53-abnormal, and no specific molecular profile)] reflecting the Tumor Cancer Genomic Atlas Research Network subgroups in endometrial carcinomas, improving the clinical applicability of molecular classification. We have analyzed the histopathologic and prognostic characteristics of our cases based on the ProMisE classification, supported by growing data on recommended treatment regimens. The study included 118 cases of endometrial carcinoma diagnosed between 2016 and 2020, which underwent mismatch repair and p53 immunohistochemistry. Next-generation sequencing was performed for POLE mutation analysis, dividing the cases into 4 subgroups. The histopathologic and clinical characteristics of these groups were then analyzed statistically. Four cases(3.4%) were classified as POLE mutant, 31 (26.3%) as mismatch repair-deficient, 22 (18.6%) as p53 mutant, and 61 (51.7%) as no specific molecular profile. We categorized 118 patients with endometrial carcinoma into low (n=43), intermediate (n=28), high-intermediate (n=21), high (n=22), and advanced metastatic (n=4) risk groups regardless of the molecular subtypes of their disease. When we reclassified all cases according to the molecular subtypes of endometrial carcinoma only the risk group of 3 (2.5%) cases changed. Using the new algorithm we designed, after narrowing down the number of patients, the microcystic, elongated, and fragmented pattern of invasion was revealed as an independent prognostic factor that reduces overall survival time (hazard ratio: 16.395, 95% CI: 2.140-125.606, P =0.007). In conclusion, using the new algorithm we have designed, and by identifying patients for whom molecular classification could alter risk groups, we observed that molecular tests can be utilized more efficiently in populations with limited economic resources and, in doing so, we discovered a new morphologic marker with prognostic significance.

Intracranial solitary fibrous tumors: Clinical, radiological, and histopathological insights along with review of literature

BackgroundIntracranial solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms, often challenging to diagnose due to their resemblance to meningiomas and other central nervous system tumors. While advancements in molecular genetics have aided in classification, diagnostic nuances and optimal management strategies remain areas of interest. Materials and methodsThis retrospective study analyzed 11 cases of intracranial SFTs treated at a neurosurgical centre in India between February 2020 and January 2024. Clinical data, radiological findings, histopathological features, and follow-up details were reviewed. Immunohistochemistry, particularly STAT6, facilitated diagnosis confirmation. ResultsThe median age of presentation was 32 years, with a male predominance. Headache was the most common presenting symptom, often leading to misdiagnosis as meningiomas on radiological imaging. Histologically, SFTs exhibited spindle to ovoid cells with staghorn vessels and collagenized stroma, posing challenges in differential diagnosis. WHO grading predominantly revealed grade 1 tumors, though recurrence occurred, emphasizing the importance of long-term follow-up. Immunohistochemistry, particularly STAT6, played a pivotal role in distinguishing SFTs from other entities. ConclusionIntracranial SFTs present diagnostic challenges due to overlapping features with other tumors, warranting a comprehensive approach integrating clinical, radiological, and histopathological findings. Immunohistochemistry, particularly STAT6, emerges as a valuable diagnostic tool. Long-term follow-up is essential for monitoring recurrence and potential malignant transformation. Further research is needed to delineate optimal treatment strategies, including the role of radiotherapy in SFT management.

Citrullinated Histone H3, a Marker for Neutrophil Extracellular Traps, Is Associated with Poor Prognosis in Cutaneous Squamous Cell Carcinoma Developing in Patients with Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare severe hereditary skin disease characterized by skin and mucosa fragility, resulting in blister formation. The most severe complication in RDEB patients is the development of cutaneous squamous cell carcinoma (SCC), leading to premature death. There is a great deal of evidence suggesting a permissive tumor microenvironment (TME) as a driver of SCC development in RDEB patients. In a cohort of RDEB patients, we characterized the immune profiles of RDEB-SCCs and compared them with clinical, histopathological, and prognostic features. RDEB-SCCs were subdivided into four groups based on their occurrence (first onset or recurrences) and grading according to clinical, histopathological parameters of aggressiveness. Thirty-eight SCCs from 20 RDEB patients were analyzed. Five RDEB patients experienced an unfavorable course after the diagnosis of the first SCC, with early recurrence or metastasis, whereas 15 patients developed multiple SCCs without metastasis. High-risk primary RDEB-SCCs showed a higher neutrophil-to-lymphocyte ratio in the tumor microenvironment and an increased proportion of neutrophil extracellular traps (NETs). Additionally, citrullinated histone H3, a marker of NETs, was increased in the serum of RDEB patients with high-risk primary SCC, suggesting that this modified form of histone H3 may serve as a potential blood marker of unfavorable prognosis in RDEB-SCCs.

Forensic analysis of hydrogen sulfide poisoning cases: Innovative LC-MS/MS methodology for accurate detection in human blood

Identification of hydrogen sulfide poisoning cases has long been a challenging issue in the field of forensic science. Due to the relatively limited histopathological features associated with hydrogen sulfide poisoning, traditional anatomy faces difficulties in accurately determining such cases. Additionally, existing detection methods have inherent limitations, including complex analytical processes and low sensitivity. This research uses the principle of the reaction between triazine and hydrogen sulfide to generate thiadiazine to measure hydrogen sulfide levels in the blood, applying this method to practical case examinations. A 0.2 mL blood sample is taken and diluted with 0.8 mL saturated borax solution. In a test tube, 1 mL acetonitrile solution containing 0.1 % formic acid is taken, followed by the sequential addition of 0.1 mL diluted solution and 0.1 mL 1 % triazine aqueous solution. After thorough mixing, the mixture is allowed to stand for 30 min, during which hydrogen sulfide undergoes a derivative reaction with triazine, producing thiazine. Subsequently, the sample undergoes centrifugation and membrane filtration, and the resulting solution is analyzed using Liquid Chromatograph Mass Spectrometer. The results reveal a strong linear relationship of hydrogen sulfide within the concentration range of 10 to 2000 ng/mL, with an R2 of 0.9989. The detection limit is 3 ng/mL, and the quantification limit is 10 ng/mL. In six cases of hydrogen sulfide poisoning, the presence of hydrogen sulfide in the blood of all deceased individuals is detected, with concentrations ranging from 0.25 to 0.79 μg/mL. For the first time, this study establishes an LC-MS/MS method for determining hydrogen sulfide in blood, meeting the detection requirements for hydrogen sulfide poisoning cases.

Malignant phyllodes: 10 year review of management through a sarcoma service

BackgroundPhyllodes tumours of the breast are rare, and their treatment is still subject to discussion. They are classified as benign, borderline, or malignant based on histopathological characteristics of the stroma. This study demonstrates 10 years’ experience in diagnosis and management of malignant phyllodes. MethodsAll patients referred for discussion at our sarcoma multidisciplinary team meeting from 2003 to 2013 with a diagnosis of malignant phyllodes were identified. Patient demographics, biopsy details, excision extent, final pathology, reconstruction, adjuvant treatment, recurrence and overall survival were assessed. ResultsThirty patients were identified over the 10 year period. Eight (26.7 %) had their diagnosis upgraded to malignant phyllodes on completion excision, compared to initial biopsy. Nine (30 %) had breast surgery elsewhere as definitive treatment before referral to our service. Four of these (44.4 %) required more extensive excision and three developed metastases (33.3 %) and died. Twenty-one patients had primary surgery through our service and three (14.3 %) died from disease. Overall, 13 patients had radical mastectomy, 92.3 % with adequate margins (>1 cm histologically) and no local recurrence, 9 simple mastectomy 22.2 % with adequate margins and 1 local recurrence and 8 wide local excision with 37.5 % adequate margins and 1 local recurrence. ConclusionFor malignant phyllodes patients, the best chance to reduce recurrence and improve survival is adequate excision and radical mastectomy should be considered. For borderline lesions, consideration should be given for referral to a specialist centre and we recommend delayed reconstruction, because of the chance of histological upgrade to malignancy.

Combining morphological and functional imaging parameters to diagnose primary bone neoplasms in the skull base, spine and sacrum.

Morphological magnetic resonance (MR) and computed tomography (CT) features are used in combination with histology for diagnosis and treatment selection of primary bone neoplasms. Isolated functional MRI parameters have shown potential in diagnosis. Our goal is to facilitate diagnosis of primary bone neoplasms of the skull base, mobile spine and sacrum, by a comprehensive approach, combining morphological and functional imaging parameters. Pre-treatment MR of 80 patients with histologically proven diagnosis of a primary bone neoplasm of the skull base, mobile spine and sacrum were retrospectively analyzed for morphological and functional MRI parameters. Functional parameters were measured in 4 circular regions of interest per tumor placed on non-adjacent scan slices. Differences in values of functional parameters between different histologies were analyzed with Dunn's test. Chordomas were the predominant histology (60.0%). Most neoplasms (80.0%) originated in the midline and had geographical (78.2%) bone destruction. Amorphous-type calcification (pre-existing bone) was seen only in chordomas. Homogeneous contrast enhancement pattern was seen only in chondrosarcoma and plasmacytoma. Ktrans and Kep were significantly lower in both chordoma, and chondrosarcoma compared to giant cell tumor of the bone (p = 0.006 - 0.011), and plasmacytoma (p = 0.004 - 0.014). Highest diffusion-weighted MRI apparent diffusion coefficient (ADC) values corresponded to chondrosarcoma and were significantly higher to those of chordoma (p = 0.008). We identified the most discriminating morphological parameters and added functional MR parameters based on histopathological features that are useful in making a confident diagnosis of primary bone neoplasms in the skull base, mobile spine and sacrum.

Characterisation of phenotypic patterns in equine exercise-associated myopathies.

Equine exercise-associated myopathies are prevalent, clinically heterogeneous, generally idiopathic disorders characterised by episodes of myofibre damage that occur in association with exercise. Episodes are intermittent and vary within and between affected horses and across breeds. The aetiopathogenesis is often unclear; there might be multiple causes. Poor phenotypic characterisation hinders genetic and other disease analyses. The aim of this study was to characterise phenotypic patterns across exercise-associated myopathies in horses. Historical cross-sectional study, with subsequent masked case-control validation study. Historical clinical and histological features from muscle samples (n = 109) were used for k-means clustering and validated using principal components analysis and hierarchical clustering. For further validation, a blinded histological study (69 horses) was conducted comparing two phenotypic groups with selected controls and horses with histopathological features characterised by myofibrillar disruption. We identified two distinct broad phenotypes: a non-classic exercise-associated myopathy syndrome (EAMS) subtype was associated with practitioner-described signs of apparent muscle pain (p < 0.001), reluctance to move (10.85, p = 0.001), abnormal gait (p < 0.001), ataxia (p = 0.001) and paresis (p = 0.001); while a non-specific classic RER subtype was not uniquely associated with any particular variables. No histological differences were identified between subtypes in the validation study, and no identifying histopathological features for other equine myopathies identified in either subtype. Lack of an independent validation population; small sample size of smaller identified subtypes; lack of positive control myofibrillar myopathy cases; case descriptions derived from multiple independent and unblinded practitioners. This is the first study using computational clustering methods to identify phenotypic patterns in equine exercise-associated myopathies, and suggests that differences in patterns of presenting clinical signs support multiple disease subtypes, with EAMS a novel subtype not previously described. Routine muscle histopathology was not helpful in sub-categorising the phenotypes in our population.

Unraveling Complexity: Delving into a Novel Pigmented Epithelioid Melanocytoma Case

Abstract Pigmented epithelioid melanocytoma (PEM) is a rare and diagnostically challenging skin neoplasm. Differentiating this lesion from melanoma is challenging due to overlapping clinical, histopathological, and immunohistochemical features. Some PEMs have a benign course, while others may be associated with more aggressive behaviour and have potential for local recurrence or distant metastasis. So, careful evaluation and follow-up are crucial for individuals with a diagnosis of PEM. This case study focuses on a 42-year-old woman with a gradually enlarging, dark, pigmented gluteal lesion. Histopathological analysis following complete excision showed nodular proliferation of spindled and epithelioid melanocytes in the dermis, extending into subcutaneous fat. Cellular atypia or mitotic figures were absent, confirming the diagnosis as PEM. This case underscores the intricate balance between monitoring and intervention in complex dermatological cases, shedding light on diagnostic challenges and ultimately striving for improved patient care.

Uterine tumors resembling ovarian sex cord tumors: A retrospective analysis of 7 cases from a single institution.

To investigate the clinicopathological features, diagnosis, surgical treatment and prognosis of uterine tumors similar to ovarian sex cord tumors (UTROSCT). The clinical data, surgical approach, histopathological, and immunohistochemical features of 7 cases of UTROSCTs were retrospectively reviewed and followed up. All 4 patients were premenopausal women. The most common clinical presentation was menorrhagia (n = 4) followed by postmenopausal lower abdominal mass (n = 2) and postmenopausal bleeding (n = 1). Gynecological ultrasonography suggested uterine fibroids in 4 cases, adenomyosis with uterine fibroids in 2 cases, and an intrauterine mass in 1 case. Pelvic MRI was performed preoperatively in only 2 cases, and both indicated uterine fibroid degeneration, including 1 patient with suspected malignancy. Preoperative serum tumor markers were measured in 6 patients, and only 1 patient had elevated CA125 levels, up to 158 U/mL. Total hysterectomy with bilateral adnexectomy or salpingectomy was the most common treatment pattern (n = 6). The tumors were located within the myometrium (n = 4), submucosa (n = 1), and isthmus to external cervical os (n = 1), with a range of 2 to 12 (mean = 8) cm. Edema and degeneration were observed in 2 cases, and necrosis in 1 case. Postoperative follow-up ranged from 31 to 82 (mean = 43) months. Unfortunately, 1 patient died at 54 months of follow-up without undergoing hysterectomy. The remaining 6 cases showed no tumor recurrence or metastasis after surgery. Histological examination revealed a tumor composed of epithelioid tumor-like cells arranged in cords, trabeculae, and nests. All 7 tumors showed expression of 2 sex cord differentiation markers. Furthermore, all tumors expressed the smooth muscle marker, while epithelial marker CK (4/7). endometrial stromal marker CD10(0/7). The Ki-67 proliferation index was found to be <5% (5/7). The option of total hysterectomy may be considered for women who do not have any fertility requirements. However, for young women who desire to maintain their reproductive capacity, surgery to preserve the uterus may be an alternative, although it necessitates careful postoperative monitoring. In terms of follow-up monitoring, MRI is more suitable than ultrasound. The diagnosis of UTROSCT heavily relies on histopathological examination and immunohistochemical analysis.

TPPP-BRD9 fusion-related gallbladder carcinomas are frequently associated with intracholecystic neoplasia, neuroendocrine carcinoma, and a distinctive small tubular-type adenocarcinoma commonly accompanied with a syringomatous pattern

A fusion between tubulin polymerization-promoting protein (TPPP), a regulatory cytoskeletal gene, and the chromatin remodeling factor, bromodomain-containing protein 9 (BRD9), TPPP-BRD9 fusion has been found in rare cancer cases, including lung and gallbladder cancers (GBC). In this study, we investigated the histopathological features of 16 GBCs previously shown by RNA sequencing to harbor the TPPP-BRD9 fusion. Findings in the fusion-positive GBCs were compared with 645 GBC cases from the authors’ database. Among the 16 TPPP-BRD9 fusion-positive GBC cases, most were females (F:M = 7:1) of Chinese ethnicity (12/16), whereas the remaining cases were from Chile. The histopathological examination showed the following findings: 1) Intracholecystic neoplasm (ICN) in 7/15 (47% vs. 7% 645 reference GBCs, p < 0.001), all with gastro-pancreatobiliary phenotype, often with clear cell change, and in the background of pyloric gland metaplasia and extensive high-grade dysplasia. 2) Neuroendocrine carcinoma (NEC) morphology: 3 cases (27% vs. 4.6% in the reference database, p = 0.001) showed a sheet-like and nested/trabecular growth pattern of monotonous cells with salt-and-pepper chromatin characteristic of NECs. Two were large cell type, one had prominent clear cell features, a rare finding in GBNECs; the other one had relatively bland, well-differentiated morphology, and the remaining case was small cell type. 3) Adenocarcinoma identified in 8 cases had a distinctive pattern characterized by widely separated small, round tubular units with relatively uniform nuclei in a fashion seen in mesonephric adenocarcinomas, including hobnail-like arrangement and apical snouts, reminiscent of tubular carcinomas of the breast in many areas. In some foci, the epithelium was attenuated, and glands were elongated, some with comma shapes, which along with the mucinous/necrotic intraluminal debris created a “syringoid” appearance. 4) Other occasional patterns included the cribriform, glomeruloid patterns, and metaplastic tubular-spindle cell pattern accompanied by hemorrhage. In conclusion, TPPP-BRD9 fusion-positive GBCs often develop through intracholecystic neoplasms (adenoma-carcinoma sequence) of gastro-pancreatobiliary lineage, appear more prone to form NEC morphology and have a propensity to display clear cell change. Invasive adenocarcinomas arising in this setting often seem to display a distinctive appearance that we tentatively propose as the TPPP-BRD9 fusion-positive pattern of GBC.

YAP1∷KMT2A fusion-positive sarcoma: An emerging soft tissue tumor entity with morphological features resembling a sclerosing epithelioid fibrosarcoma.

Sclerosing epithelioid fibrosarcoma (SEF) and low-grade fibromyxoid sarcoma (LGFMS) constitute a morphological continuum with certain overlapping histopathological features and MUC 4 immunopositivity. SEF is characterized by EWSR1 gene rearrangement, is relatively more aggressive and shows a limited response to chemotherapy. Lately, a subset of tumors with morphological features of SEF, but lacking MUC4 immunostaining and EWSR1 gene rearrangement have been observed. We report the first case of YAP1∷KMT2A-positive sarcoma from the Indian subcontinent along with a review of similar tumors reported previously. A case of 31-year-old male presented with a 3 cm painful lump in the right suboccipital region. Histopathological examination of the excised specimen revealed a cellular tumor composed of atypical spindle and epithelioid cells, exhibiting moderate nuclear pleomorphism, arranged in cords, embedded in a dense collagenous/hyalinized stroma. By immunohistochemistry, the tumor cells were diffusely positive for cyclin D1 and negative for MUC4, desmin, myogenin, β-catenin, STAT6, myoD1, SMA, and S100P. By fluorescence in-situ hybridization, EWSR1 gene rearrangement was negative. Next-generation sequencing (NGS) revealed YAP1exon5∷KMT2Aexon4 fusion. Given a positive resection margin, he underwent a revision surgery involving wide local excision of the lesion including the outer table of the occipital bone followed by image-guided radiation therapy. Over 2 years of his follow-up, the patient is alive with no evidence of recurrence. Thus, YAP1∷KMT2A positive sarcomas have distinct molecular and overlapping histopathological features with SEF, with relatively less aggressive disease course. Documentation of additional similar tumors with long-term follow-up is required.