Histomorphological Features Research Articles

The importance of histomorphological features and ERG expression in the diagnosis of malignancy in cases with atypical small acinar proliferation.

Atypical small acinar proliferation (ASAP) cases typically require rebiopsy, which are invasive and associated with increased risk of complications. Our aim in this study was to determine the importance of laboratory and histological findings and E-26 transformation-specific-related gene (ERG) expression in the diagnosis of malignancy. Between March 2016 and March 2022, 84 patients who were diagnosed with ASAP on biopsy or rebiopsy were included in the study. Clinical-laboratory features of age, serum prostate-specific antigen level, and histopathological features were compared and included multifocality, number of suspicious acini, nuclear enlargement, nucleolar prominence, hyperchromasia, cytoplasmic amphophilia, luminal amorphous acellular secretion, crystalloid presence, infiltrative appearance, inflammation, atrophy, α-methyl acyl-CoA racemase, p63, and/or high molecular weight cytokeratin were analyzed. In addition, ERG expression was evaluated immunohistochemically. Statistically significant correlation was found between nucleolar prominence, nuclear hyperchromasia, crystalloid presence, infiltrative pattern, and prostate cancer (p < .001). In 19 of 84 cases (22.6%) ERG was positive in the nucleus. Prostate cancer was diagnosed at rebiopsy in 15 of the 19 ERG-positive cases (78.9%). A statistically significant correlation was found between ERG positivity and prostate cancer (p= .002). Our findings suggest that evaluation of these markers during initial transrectal ultrasound biopsies may decrease and prevent unnecessary prostate rebiopsy.

Galectin-3 expression by thyroid neoplasms in a center in southwest Nigeria

Background: Galectin-3 (GAL-3), which is known to be expressed in certain normal tissues and is implicated in tumor progression and metastasis, serves as a valuable marker for distinguishing malignant thyroid lesions from benign thyroid lesions. This study aimed to assess the clinical and histopathological features of thyroid neoplasms at OAUTHC Ile Ife utilizing GAL-3 immunohistochemistry and to compare these findings with those of studies conducted in other regions of the world. Materials and Methods: Histology slides from 56 patients with thyroid neoplasms spanning a 20-year period were subjected to immunohistochemical staining with monoclonal antibodies against GAL-3. Evaluation was based on the 2022 World Health Organization Classification of Thyroid Neoplasms, categorizing marker expression as follows: 1+ (10–25% stained cells), 2+ (26–50% stained cells), 3+ (51–75% stained cells), and 4+ (&gt;75% stained cells). Negative staining indicated no staining, while localized staining (focal) represented &lt;50% of cells stained (1+ or 2+), and diffuse staining indicated &gt;50% of cells stained (3+ or 4+). Results: A total of 56 patients with neoplastic thyroid disease were studied, including 15 males and 41 females. Among the 16 benign neoplastic lesions, four (25.0%) exhibited focal GAL-3 expression, while 12 (75.0%) showed no expression. Among the forty malignant neoplastic lesions, five (12.5%) tested negative for the GAL-3 immunomarker, while 35 (87.5%) demonstrated positive expression to varying degrees. Among the positive malignant lesions, two (5.0%) displayed focal GAL-3 expression, while 33 (82.5%) exhibited diffuse staining of tumor cells. The diffuse and strong expression of GAL-3 was significantly greater in malignant thyroid neoplasms than in benign neoplasms (p&lt;0.05). The sensitivity and specificity of GAL-3 were 88% and 75%, respectively. Conclusion: Our findings align with the previous research indicating that diffuse and strong immunohistochemical expression of GAL-3 is indicative of thyroid gland malignancy. GAL-3 serves as a valuable tool in diagnosing thyroid neoplasms, particularly in cases where histomorphologic characteristics are inconclusive or unclear.

An Evaluation of High-Risk HPV in Squamous Cell Carcinomas of the Lip in a South African Cohort

BackgroundTo determine the prevalence of HR-HPV in a series of lip SCC from South African patients, using currently accepted HPV-testing methodologies and to define the clinical and histomorphologic features of HPV-associated lip SCC.MethodsFifty SCC of lip and 50 control cases were tested for HR-HPV using p16 and HR-HPV DNA PCR. p16-equivocal/positive and HPV DNA PCR-positive SCC were further evaluated for the expression of HPV-16 and HPV-18 mRNA transcripts using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to confirm transcriptionally active HPV.Resultsp16 was positive in 22% (n = 11) and equivocal in 4% (n = 2) of the SCC. One p16-positive case showed positivity for both HPV-16 DNA and HPV-16 E6/E7 mRNA transcripts (HPV prevalence rate of 2%). The HPV-positive case was non-keratinizing and occurred in an 80-year-old female. The two p16-equivocal cases were HR-HPV DNA positive and mRNA PCR negative. p16 was found to have a positive predictive value of 9%.ConclusionFindings from our cohort of lip SCC suggest that HR-HPV may have an insignificant role in the pathogenesis of SCC at this site. Due to its low ppv, p16 is insufficient to establish HR-HPV infection in SCC of the lip. The combination of p16 and DNA PCR appears to correlate with the presence of transcriptionally active virus. HPV E6/E7 mRNA detection is the gold standard for identifying HR-HPV. mRNA testing is not widely available in sub-Saharan Africa due to technical and financial constraints; however, the test appears to be of great value in p16-equivocal lip SCC.

Histomorphological Spectrum of Lung Lesions in Medico- legal Autopsy in a Tertiary Care Centre

Background: Organ specific pathological changes seen during autopsy give a clear idea of the cause of death. Lungs are one of the most important vital organs in the human body. They are almost always involved in terminal events of cardiovascular diseases.Autopsy is important not only to know the state of lungs but also to study the morphology of various diseases.Various studies have demonstrated that,20-30% of sudden deaths are due to underlying pulmonary pathology. Aims and objectives: The significance of this study is to highlight the spectrum of histomorphological features of lung lesions in medico-legal autopsies irrespective of cause of death. Material and Methods:This was a retrospectivestudy Medico legal autopsies over a period of 5 years carried out in the Department of Pathology in coordination with the Department of Forensic Medicine, Gulbarga Institute of Medical Sciences. Standard protocols are used for gross and histopathology processing. Results: After thorough histopathological examination, of total 100 cases, various lesions were identified in 93 cases, in 7 cases tissue was autolyzed. Majority cases seen in the age group of 20-40yrs with male predominance. The most common cause of death was Road Traffic Accident (RTA) and majority victims were males. The commonly observed pathological features congestion and oedema(44.4%), Pneumonia(26.8%),CVC(22.2%) tuberculosis(9.6%) and ARDS(6.6%). Conclusion: The present study observed and documented histomorphological spectrum of lung lesions in medico-legal autopsies and highlighted various pathological conditions which are either direct or indirect cause of death. This study emphasizes that spectrum of histopathological changes in lungs of autopsy cases irrespective of cause of death and highlights some incidental interesting findings in lungs.

Proteomics-Derived Biomarker Panel Facilitates Distinguishing Primary Lung Adenocarcinomas With Intestinal or Mucinous Differentiation From Lung Metastatic Colorectal Cancer

The diagnosis of primary lung adenocarcinomas with intestinal or mucinous differentiation (PAIM) remains challenging due to the overlapping histomorphological, immunohistochemical (IHC), and genetic characteristics with lung metastatic colorectal cancer (lmCRC). This study aimed to explore the protein biomarkers that could distinguish between PAIM and lmCRC. To uncover differences between the two diseases, we used tandem mass tagging–based shotgun proteomics to characterize proteomes of formalin-fixed, paraffin-embedded tumor samples of PAIM (n = 22) and lmCRC (n = 17).Then three machine learning algorithms, namely support vector machine (SVM), random forest, and the Least Absolute Shrinkage and Selection Operator, were utilized to select protein features with diagnostic significance. These candidate proteins were further validated in an independent cohort (PAIM, n = 11; lmCRC, n = 19) by IHC to confirm their diagnostic performance. In total, 105 proteins out of 7871 proteins were significantly dysregulated between PAIM and lmCRC samples and well-separated two groups by Uniform Manifold Approximation and Projection. The upregulated proteins in PAIM were involved in actin cytoskeleton organization, platelet degranulation, and regulation of leukocyte chemotaxis, while downregulated ones were involved in mitochondrial transmembrane transport, vasculature development, and stem cell proliferation. A set of ten candidate proteins (high-level expression in lmCRC: CDH17, ATP1B3, GLB1, OXNAD1, LYST, FABP1; high-level expression in PAIM: CK7 (an established marker), NARR, MLPH, S100A14) was ultimately selected to distinguish PAIM from lmCRC by machine learning algorithms. We further confirmed using IHC that the five protein biomarkers including CDH17, CK7, MLPH, FABP1 and NARR were effective biomarkers for distinguishing PAIM from lmCRC. Our study depicts PAIM-specific proteomic characteristics and demonstrates the potential utility of new protein biomarkers for the differential diagnosis of PAIM and lmCRC. These findings may contribute to improving the diagnostic accuracy and guide appropriate treatments for these patients.

Congenital spindle cell/sclerosing rhabdomyosarcoma: a clinicopathological analysis

Objective: To investigate the clinicopathological features, immunophenotype and molecular genetic characteristics of congenital spindle cell/sclerosing rhabdomyosarcoma. Methods: Sixteen cases (including 10 consultation cases) of congenital spindle cell/sclerosing rhabdomyosarcoma diagnosed at the Beijing Children's Hospital, Capital Medical University, Beijing China, from April 2017 to January 2022 were collected. These cases were evaluated for clinical profiles, histomorphological features, immunophenotype and molecular characteristics. Results: Among the 16 patients, 9 were male and 7 were female. Five cases were present during maternal pregnancy and 11 cases were found immediately after birth. The tumors were located in the chest wall, low back, retroperitoneum, extremities or perineum. The tumors consisted of fasciculated spindle-shaped cells with localized mesenchymal sclerosis and vitreous metaplasia. Immunohistochemistry showed that the tumor cells expressed Desmin, Myogenin, MyoD1, SMA, CD56 and ALK to varying degrees, but not other markers such as CD34, CD99, pan-TRK, S-100 and BCOR. FISH analyses with NCOA2 (8q13) and VGLL2 (6q22) gene breakage probes revealed a breakage translocation in chromosome NCOA2 (8q13) in 4 cases (4/11). In the 6 cases subject to sequencing, a mutation at the p.L122R locus of MYOD1 gene was detected in 1 case (1/6). Two cases were examined by electron microscopy, which showed bundle-arranged myofilaments with some primitive myofilament formation. Five cases were resected with simple surgery, 2 cases were biopsied and followed up with observation only, and 9 cases were treated with surgery and adjuvant chemotherapy. Follow-up was available in 12 cases. At the end of the follow-up, 2 of the 12 patients developed local recurrences and 2 patients survived with disease. Conclusions: Congenital spindle cell/sclerosing rhabdomyosarcoma is a rare subtype of congenital rhabdomyosarcoma. It more commonly occurs in the chest, back and lower limbs of infants than other sites. NCOA2/VGLL2 gene fusion seems to be the most common genetic change. Its prognosis is better than other subtypes of rhabdomyosarcoma and those in adolescents and adults with the same subtype. Analysis and summary of its clinicopathological features can help differentiate it from other soft tissue tumors in infants and children and provide the information for appropriate treatments.

Role of P63 in Benign and Malignant Lesions of Breast

Introduction: Breast carcinoma is leading cause of cancer death in women. Breast lesions constitute heterogeneous group of diseases with wide variety of etiologies ranging from inflammatory-benign- malignant lesions. There are several reported markers for immunohistochemical detection of myoepithelial cells. Smooth muscle specific proteins, such as smooth muscle actin, smooth muscle myosin heavy chain, calponin and h-caldesmon are used to highlight myoepithelium. p63 antibody is myoepithelial cell marker that selectively stains nuclei. It is negative in stromal, myofibroblastic and adipocytic cells.Aims and Objectives: The aim of this study was to establish role of p63 expression in distinguishing benign breast lesions, premalignant lesions and malignant tumors of breast.Materials and Methods: 30 cases were selected from core biopsy, lumpectomy and mastectomy specimens ofbreast received at department of Pathology, Chalmeda Anand Rao Institute of Medical Sciences during the period of January 2021 to December 2021 and were studied prospectively. All specimens were processed according to CAP protocol and reported . Immunohistochemistry was performed to determine p63 expression in those specimens. p63 expression was evaluated as continuous positive/discontinuous positive/negative.Ethical Approval: This study was reviewed and approved by institute ethics committee, CAIMS, Karimnagar.Results: Among total 30 cases, 18 cases (60%) were benign lesions and all were positive for p63 expression. 3 cases (9.99%) were premalignant and were least positive for p63 expression. All malignant cases 9 cases (29.99%) were negative for p63 expression.Conclusion: The Positive correlation was seen between histomorphological features and p63 scoring in all the lesions, So p63 is good Immunohistochemical marker for evaluating breast lesions.

Feline Facial Spindle Cell Tumors in 29 Cats: Histomorphological and Immunohistochemical Characterization.

Soft tissue tumors/sarcomas (STSs) in felines, encompassing a variety of mesenchymal tumors with similar histomorphological features, present diagnostic challenges due to their diverse cellular origins and the overlap with other tumor types such as feline sarcoid. This study aimed to delineate the clinical, histomorphological, and immunohistochemical characteristics of 34 feline facial spindle cell tumors affecting 29 cats, including testing for bovine papillomavirus type 14 (BPV14), the virus causing feline sarcoids. Only five out of 12 tumors previously diagnosed as feline sarcoids based on histomorphology were confirmed by PCR for BPV14, underscoring the importance of comprehensive diagnostic approaches to accurately distinguish between STSs and feline sarcoids. This study shows that most facial spindle cell tumors were compatible with peripheral nerve sheath tumors (PNSTs) based on positive immunohistochemical staining for Sox10 and other immunohistochemical markers such as GFAP, NSE, and S100. Some of these tumors displayed as multiple independent masses on the face or as erosive and ulcerative lesions without obvious mass formation, an atypical presentation and an important highlight for general practitioners, dermatologists, and oncologists. This study also describes periadnexal whorling of neoplastic cells as a novel histomorphologic finding in feline facial PNSTs and emphasizes Sox10 as a useful complementary immunohistochemical marker for the diagnosis of facial PNST in cats, providing valuable insights for veterinary pathologists.

Immunohistochemical marker profiles for the differentiation of collagenous spherulosis from adenoid cystic carcinoma of the breast

Collagenous spherulosis (CS) is a rare breast lesion of unknown histogenesis. Adenoid cystic carcinoma (ACC) is a rare basal-like breast carcinoma with low histological grade. CS is a benign lesion but resembles ACC. Both lesions show a similar histomorphology and feature bilineage differentiation. This study compared immunohistochemical markers in CS and ACC.We compiled n = 13 CS cases and n = 18 mammary ACCs. Fourteen marker proteins (ER, PR, HER2, GATA3, CK7, E-cadherin, CD117, CK5/14, p40, p63, SMA, CD10, calponin, P-cadherin) were evaluated by immunohistochemistry (IHC). MYB rearrangement, a common alteration in ACC, was assessed by fluorescence in situ hybridization.Patient age ranged between 40-60 years for CS lesions and 30–90 years for ACCs. 7/13 (54%) CS cases harbored a lobular carcinoma in situ (LCIS) in the luminal component. One CS/LCIS lesion occurred in a carrier of a pathogenic germline variant in CDH1/E-cadherin. MYB rearrangement was detected in 0/11 (0%) CS and 6/16 (37%) ACC cases (P = 0.054). CS was associated with expression of ER in the luminal component (P < 0.001), E-cadherin loss in the luminal component (P = 0.045), and expression of CD10 and calponin in the basal component (P < 0.001). Furthermore, CS was associated with GATA3 expression in the luminal component (12/13 [92%] versus 5/18 [27%], P < 0.001).In summary, IHC for GATA3 and E-cadherin may contribute to the differential diagnosis between CS and ACC, although these markers are not exclusively expressed in either lesion. Histologic evaluation has to take into account that CS is frequently colonized by LCIS, requiring thorough correlation of histomorphology and immunohistochemical features.

Evaluation of the histologic and immunohistochemical (CD34, glutamine synthetase) findings in idiopathic non-cirrhotic portal hypertension (INCPH)

AimIdiopathic non-cirrhotic portal hypertension (INCPH) is a vascular disorder of uncertain origin. Diagnosis can be challenging on liver biopsy. Despite diverse histomorphologic findings documented in literature, studies on the frequency of these findings are lacking. This study aims to assess both the histomorphologic features and the immunoexpression patterns of CD34 and glutamine synthetase (GS) in liver biopsies and searched for their contribution to the pathologic diagnosis of INCPH.Materials and methodsHematoxylin–eosin, CD34, and GS-stained liver needle biopsy sections of 16 patients clinically diagnosed with INCPH were retrospectively analyzed. Histologic findings such as portal vein narrowing, obliteration, or loss were grouped as major findings, while portal vein herniation, hypervascularized portal tracts, and periportal abnormal vessels were grouped as minor findings, and their frequency were evaluated. Periportal endothelial CD34 stained areas were measured via ocular micrometer. The distribution of GS immunoexpression was evaluated. Eighteen healthy liver donor biopsies were evaluated as controls.ResultsIn INCPH cases, 58% of portal tracts showed major findings, compared to 15% in the control group (p < 0.001). Minor findings were observed in 16% of INCPH cases and 7% of controls (p = 0.014). The number of portal tracts with histologic findings is significantly higher in INCPH than in control liver biopsies. Abnormal portal tract distribution, like being close to each other, was seen in 75% of INCPH cases but not in controls (p < 0.001). Nodular regenerative hyperplasia (NRH) was present in 31% of cases. Periportal CD34 expression was higher in INCPH, and affected areas were larger than in controls (p < 0.001). Irregular GS staining, i.e. GS staining with patchy distribution in zone 3, and/or periportal and zone 2 hepatocytes, was found in 62% of INCPH cases, while controls showed the usual pattern (p < 0.001).ConclusionIn the biopsy diagnosis of INCPH, in addition to the presence of major histologic findings and the amount of portal tracts displaying these features, the expression of endothelial CD34 in periportal areas, and irregular hepatocellular GS expression can also be considered as supporting feature.

Abstract 2335: MultiNMF: multiview factorization for joint modeling of spatial multi-omics and histology images

Abstract An increasing number of cancer research studies employ spatially resolved transcriptomics (SRT) to investigate the composition of tumor microenvironment in a cancer type of interest. These studies have defined tumor microenvironment (TME) states and spatial domains based on clustering spatial gene expression patterns in SRT in an unbiased manner, yet a more thorough delineation of TME states requires the incorporation of the tumor’s histology image. Here, we develop MultiNMF, a multiview factorization approach that is suitable for cancer research studies where joint profiles of spatial multi-omics and tumor histology images are available. We apply MultiNMF to analyze a set of TNBC SRT primary tumor samples and reveal TME states in the stromal, epithelial, and immune enriched compartments, defined by distinct histomorphological features. We further illustrate the ability of the approach to extend to paired spatial ATAC-seq and histology dataset that is recently published on HER2 breast cancer. MultiNMF thus permits an automated and data-driven decomposition of SRT and spatial ATAC data supported by histomorphological evidence. Context In SRT by 10X Visium, the hematoxylin eosin (H&amp;E) staining image is automatically aligned to the slide where the tissue section is mounted. Image patches can be easily extracted from areas under the SRT barcoded spots. For these images, I will apply a pre-trained convolutional neural network (CNN) model to extract high dimensional features from spot images. The image features can be added as a second view after gene expression view for joint analysis under MultiNMF. Results MultiNMF can factorize the SRT data into components well-supported by histological evidence. It has identified T-cell infiltrating regions, and EMT-enriched regions with distinct immune and stroma morphological characteristics. The T-cell infiltration neighbors a region that has an appearance of necrosis according to the pathologist evaluation. These domains further demonstrate enrichments of modules with motif enrichment (known as regulons) according to SCENIC analysis. Analysis of spatial ATAC illustrates not only HER2 but also its amplicon amplification. From MultiNMF components of spatial ATAC, we derive regulatory regions for T-cell/B-cell marker genes. Overall, MultiNMF is a novel model that has not been applied to SRT field. It provides an multiomic extension to the traditional NMF. Citation Format: William Bowie, Stacy Wang, Benjamin Strope, Qian Zhu. MultiNMF: multiview factorization for joint modeling of spatial multi-omics and histology images [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2335.

A systematic pan-cancer study on deep learning-based prediction of multi-omic biomarkers from routine pathology images.

The objective of this comprehensive pan-cancer study is to evaluate the potential of deep learning (DL) for molecular profiling of multi-omic biomarkers directly from hematoxylin and eosin (H&E)-stained whole slide images. A total of 12,093 DL models predicting 4031 multi-omic biomarkers across 32 cancer types were trained and validated. The study included a broad range of genetic, transcriptomic, and proteomic biomarkers, as well as established prognostic markers, molecular subtypes, and clinical outcomes. Here we show that 50% of the models achieve an area under the curve (AUC) of 0.644 or higher. The observed AUC for 25% of the models is at least 0.719 and exceeds 0.834 for the top 5%. Molecular profiling with image-based histomorphological features is generally considered feasible for most of the investigated biomarkers and across different cancer types. The performance appears to be independent of tumor purity, sample size, and class ratio (prevalence), suggesting a degree of inherent predictability in histomorphology. The results demonstrate that DL holds promise to predict a wide range of biomarkers across the omics spectrum using only H&E-stained histological slides of solid tumors. This paves the way for accelerating diagnosis and developing more precise treatments for cancer patients.

Histomorphological and histochemical features of atresia of antral follicles of water buffaloes

The present study aimed to characterize the atresia of antral follicles of buffalo. Two types of atresia, cystic and obliterative, were observed in the buffalo ovary. The cystic atresia was characterized by complete degeneration of the granulosa cells with the antrum filled with fluid. In obliterative atresia, the granulosa cells degenerated, and the surrounding theca cells started invaginating into the antrum. The ingrowth of these connective tissues filled the antrum. The histological picture of tertiary follicles showed that the atresia occurred in successive stages. The atretic changes observed were pyknosis of granulosa cells, the creation of small spaces between the cells, and the loosening of the cumulus oophorus cells. Two patterns were observed based on the start of atresia, i.e. antral atresia and basal atresia. At places, call-exner bodies were observed in the granulosa cell layer. The collagen fiber-containing basal lamina started separating from the theca layer at locations and later became hypertrophied in the cystic atresia type. In contrast, in the obliterative atresia, the collagen fibers were seen as abundant in growth towards the lumen and later, it filled the whole antral cavity. Disruptions of reticular fibers as stained with Gridley’s stain were observed in the cystic type of atresia, and ingrowth of reticular fibers in the antrum and formation of corpus atreticum were contributed by reticular fibers also.

Central Neurocytoma in a Teenager, a Rare Cause of Hemiplegia, and a Diagnostic Dilemma in a Resource-Poor Setting

Background. Central neurocytoma is a benign intraventricular neuroectodermal tumor most often arising in the lateral ventricles. Due to the location of this tumor, common signs and symptoms include obstructive hydrocephalus, recurrent headache, visual impairment, nausea, and vomiting. Central neurocytoma and intraventricular oligodendroglioma share similar gross features and cellular and architectural morphology, which may pose a diagnostic challenge in a poor resource setting. Immunohistochemical neuronal stains are useful for the two tumors in our setting. Report. An 18-year-old male patient presented with a 1-year history of right-sided weakness, recurrent seizures, and sudden loss of consciousness. The patient showed signs of increased intracranial pressure, but an antemortem CT or MRI scan could not be done to determine the underlying cause, due to lack of availability and poor prognosis of the patient at the time of presentation. An autopsy revealed a well-demarcated solid cystic, gritty intraventricular tumor causing obstructive hydrocephalus, with associated dilated ventricles and severe cerebral edema. Postmortem histopathological examination of the tumor confirmed central neurocytoma. Conclusion. Central neurocytoma (CN) is an uncommon cause of intracranial space occupying lesion (ICSOL) in the teenage age group in our setting. Central neurocytoma and intraventricular oligodendroglioma share similar radiologic and histomorphological features. Immunohistochemical evaluation with neuronal markers is essential in these two tumors, as they have different prognoses and surgical and treatment outcomes.

Clinicopathological study of pigmented fungal lesions with special reference to subcutaneous phaeohyphomycosis: A 3-year study in a tertiary care hospital of Eastern India

Background: Fungal infections are predominantly opportunistic infections in immunocompromised patients and in immunocompetent adults with a history of trauma. Recently, there is an increase in trends of fungal infections in immunocompetent individuals also without any history of trauma. Pigmented fungi are a group of fungi that have pigment in their cell wall and also known as dematiaceous fungi. These pigmented fungi include phaeohyphomycosis with a differential diagnosis of chromoblastomycosis, cryptococcosis, mycetoma, and aspergillus. Phaeohyphomycosis is a subcutaneous or systemic infection characterized histologically by dark-colored fungal hyphae and yeast forms (black yeast). Aims and Objectives: The aim of the present study is to analyze the clinicopathological features of pigmented fungal infections in biopsy specimen based on their histomorphology. Materials and Methods: This was a prospective study in which we have analyzed the dematiaceous fungal species by their histomorphological characteristics in biopsy specimens. Results: A total of 21 cases of biopsy specimens (with the clinical presentation of cutaneous/subcutaneous lesions) were studied histologically which showed 13 cases of phaeohyp homycosis, seven cases of eumycotic mycetoma, and one case of chromoblastomycosis. There was male predominance (17, 80.95%) and the majority of the patients were &gt;60 years (16, 76.19%). Most common site of infection was foot with predominant clinical presentation as subcutaneous mass lesion. Conclusion: All the cases of dematiaceous fungal infections were diagnosed by histopathological examination. Melanin in the cell wall of dematiaceous fungi is the pathogenic factor. Phaeohyphomycosis is no longer considered as a rare infection rather there is an increasingly incidence of recognized infection. Although culture and histopathological study remain important tools for final diagnosis, various molecular studies might be helpful for accurate diagnosis.

Papillary renal neoplasm with reverse polarity: an observational study of histology, immunophenotypes, and molecular variation.

Papillary renal neoplasm with reverse polarity (PRNRP) is a novel entity with unique clinicopathological characteristics, and only a small number of patients with PRNRP have been described. We retrospectively analyzed the data for nine patients with PRNRP and evaluated differences in the clinical, histomorphological, immunohistochemical, and molecular features; prognosis; and differential diagnosis of PRNRP from other renal tumors with papillary structure. There were six males and three females aged 36 to 74 years (mean: 62.33 years; median: 68 years). All the tumors were solitary and ranged from 1 to 3.7 cm (mean: 2.17 cm; median: 2 cm), with three and six tumors arose in the left and right renal tract, respectively. Pathologically, PRNRP is a small, well-circumscribed neoplasm with predominant papillary formations. The lining epithelium is composed of a monolayer of cuboidal to low-columnar cells with low-grade nuclei arranged against the apical pole of the tumor cells. Edema, mucinous degeneration, and hyaline degeneration are found in the fibrovascular cores. Foamy macrophages, psammoma bodies, hemosiderin deposition, and infiltrative tumor boundaries were present in some patients. Immunohistochemically, all tumors showed diffuse positive staining for GATA3. Sanger sequencing confirmed the presence of KRAS mutation in seven patients. All patients had a good prognosis after surgery and were relapse free. Positive staining for GATA3 and negative staining for vimentin were the most significant markers for differentiating PRNRP from other renal tumors with analogous structure. These findings suggested that PRNRP is a distinctive subtype of renal tumor with specific pathological features and indolent behaviors that should be distinguished from other renal tumors, especially papillary renal cell carcinoma. A monolayer of tumor cells with an inverted nuclear pattern, positive staining for GATA3, and KRAS mutation are essential for pathological diagnosis. Owing to its satisfactory prognosis, the surveillance and follow-up of patients with PRNRP should be additionally formulated.

Heterogeneity of small duct- and large duct-type intrahepatic cholangiocarcinoma.

The histological subtype of intrahepatic cholangiocarcinoma (iCCA) is associated with different mutational characteristics that impact clinical management. So far, data are lacking on the presence of small duct iCCA (SD-iCCA) and large duct iCCA (LD-iCCA) in a single patient. The aim of the current study was to determine the presence and degree of intratumoural heterogeneity of SD- and LD-iCCA features in different tumour regions. All patients treated with surgically resected iCCA at Frankfurt University Hospital between December 2005 and March 2023 were retrospectively analysed. Histomorphological features of SD- and LD-iCCA were evaluated by an expert hepatobiliary pathologist. Tissue samples suspicious for subtype heterogeneity were further investigated. Immunohistochemistry for N-cadherin, S100P, MUC5AC, MUC6, TFF1 and AGR2 and mutational profiling with the Illumina TruSight Oncology 500 (TSO500) assay were performed separately for the SD- and LD-iCCA regions. Of 129 patients with surgically resected iCCA, features of either SD- or LD-iCCA were present in 67.4% (n = 87) and 24.8% of the patients (n = 32), respectively; 7.8% (n = 10) had histomorphological features of both SD- and LD-iCCA, seven patients (5.4%) of which had sufficient formalin-fixed, paraffin-embedded tissue for further analysis. Heterogeneity of both subtypes could be confirmed with immunohistochemistry. In five of seven (71.4%) patients, molecular profiling revealed intratumoural differences in genetic alterations between the SD- and LD-iCCA region. In one patient, a BRAF mutation (p.V600E) was found in the SD-iCCA but not in the LD-iCCA region of the tumour. A marked portion of patients with iCCA exhibits both SD- and LD-iCCA in different tumour regions. In case of the presence of histopathological heterogeneity, mutational profiling should be considered to avoid missing therapeutically relevant genetic alterations.

Multicystic renal dysplasia, a histomorphological spectrum: Seven years experience from a tertiary care hospital.

Multicystic dysplastic kidney (MCDK) is defined as the presence of multiple noncommunicating cysts of various sizes, detected sonographically, without evidence of functioning renal parenchyma on dimercaptosuccinic acid renal scan. It has an incidence of 1:4000 live births. They are more commonly diagnosed in boys, usually on the left side, but may also be bilateral. There is the presence of primitive ducts surrounded by fibromuscular connective tissue. These are because of the disturbed connection of the ureteric bud with renal blastema and abnormal division at the stage of metanephros, resulting in an abnormal metanephros differentiation. Thirty cases of MCDK were included to study their histomorphology along with their clinical features. Cases were retrieved from the last seven years (2015-2021) from the Department of Pathology, Maulana Azad Medical College. Age ranged from 10 days to 18 years. The cases were between 1 years and 5 years of age. Six out of 30 cases (20%) were infants with three of them being neonates. Twenty-one cases were males. All the cases had unilateral kidney involvement with the left kidney being involved in 20 out of 30 cases. Twenty-eight cases underwent nephrectomy in view of small contracted nonfunctional kidneys with one of them being horseshoe shaped. Five cases had associated hydronephrosis (two ipsilateral and three bilateral). One case had Hirshprung's disease, four had anorectal malformation, two had posterior urethral valves with vesicourethral reflux, one had duplex moiety, and one had undescended testes. On histopathological examination, all of them showed the presence of immature disorganized tubules surrounded by a collarette of immature mesenchymal stroma. One of the cases showed osteoid formation and four had areas of immature cartilage. Normal kidney parenchyma was seen at the periphery in four cases. This series has been presented to highlight the various histomorphological features of MCDK. MCDK can be managed conservatively in most of cases due to autoinvolution and, hence, needs to be differentiated from other close differentials like polycystic kidney disease, cystic nephroma, and cystic partially differentiated nephroblastoma in order to avoid unnecessary surgical intervention.

Angiosarcoma of the head and neck: A clinicopathologic study with special emphasis on diagnostic pitfalls.

Angiosarcoma (AS) is a rare malignant vascular tumor that phenotypically and functionally recapitulate normal endothelium. They constitute approximately 2-4% of soft tissue sarcomas. We present 36 cases of head and neck AS diagnosed for 11 years at a tertiary care hospital in South India to analyze the clinical, pathological, and immunophenotypic profiles with special emphasis on their differential diagnoses and diagnostic pitfalls. Head and neck AS diagnosed from January 2006 to December 2017 were included. Clinical characteristics, treatment received, and follow-up data were obtained from electronic medical records. Hematoxylin and eosin (H&E)-stained slides and immunohistochemistry (IHC) slides were reviewed, and the histomorphological features, immunohistochemical staining, and their utility in resolving differential diagnosis were assessed. Twenty-two females and 14 males were diagnosed with head and neck AS in the study period. Histomorphological patterns observed were mixed vasoformative and solid ( n = 22), pure vasoformative ( n = 13), and pure solid ( n = 1). Neoplastic cells showed epithelioid, spindly, signet cell-like, clear cell, and rhabdoid morphology. CD31 was positive in 100% of cases, and CD34 was positive in 40% of cases. Differential diagnoses included melanoma, rhabdomyosarcoma, and large-cell lymphoma. Surgery, radiotherapy, and chemotherapy were the treatment modalities used. Twelve patients developed local recurrence, and 12 patients developed metastasis on follow-up. Twenty-five patients died of disease, on an average of 24 months after diagnosis. Head and neck AS pose a significant diagnostic challenge due to their broad morphologic spectrum. Proper clinicopathologic correlation is necessary to avoid misdiagnosis.

A snapshot of the landscape of endometrial cancer in Kenya: Implications of recent updates in pathological classification

Background: The incidence of endometrial carcinoma is rising worldwide, partly due to the risingprevalence of obesity. From a diagnostic pathology perspective, it is a heterogeneous disease with avaried range of histomorphological features and is prone to poor interobserver reproducibility. This oftenhas downstream effects on treatment protocols and patient outcomes. The current WHO Classification ofTumors of the Female Genital Tract recommends the incorporation of histology, immunohistochemistry,and molecular testing where possible in the classification of endometrial carcinoma into clinically relevantsubtypes. In Kenya, access to ancillary testing is limited and prohibitively expensive, negatively affectingaccurate tumor classification. In addition, there are limited local data on the various histologic subtypes ofendometrial carcinoma and their respective clinical outcomes.Objectives: To review the classification of endometrial carcinoma as defined by the current WHOClassification contextualized with local clinical, demographic, pathology, and outcome data from twotertiary referral centers in Kenya.Methods: Formalin-fixed paraffin-embedded blocks (FFPE) of 123 cases of endometrial carcinomasbetween 2012 and 2020 were retrieved from the Aga Khan University and Moi Teaching and ReferralHospitals. The clinical history and follow-up data were abstracted. Hematoxylin and eosin sections werereviewed and 11 immunohistochemical markers (MLH1, MSH2, MSH6, PMS2, ER, PR, ARID1A, P16,PTEN, napsin A, and p53) were determined, and analyzed to arrive at a consensus diagnosis.Results: Six endometrial carcinoma subtypes: endometrioid (68 cases, 55%), serous (32 cases, 26%),carcinosarcoma (15 cases, 12%), clear cell (5 cases, 4%), mixed carcinoma (2 cases, 1.5%), anddedifferentiated carcinoma (1 case, &lt;1%) were reported. The median age of presentation was 63 years(range of 34-90 years) and the median body mass index (BMI) was 27.4 kg/m2. Staging data wereavailable in 95 cases, of which 64 (67%) were in the early stage at presentation. Follow-up data wereavailable in 70 patients with a median follow-up time of 18 months. Recurrences were reported in 11cases, 5 of which were of the serous subtype. Of the 26 patients whose status was known at the time ofthe conclusion of the study, 7 died of the disease.Conclusion: To our knowledge, this is the first comprehensive review of the clinical and pathologicalprofiles of various subtypes of endometrial cancer in Kenya with follow-up and outcome data using awide array of immunohistochemical markers for accurate classification as per the WHO classification.