BackgroundCutaneous angiosarcoma (cutaneous AS) is a rare, aggressive endothelial malignancy characterized by rapid growth, early metastasis, and poor prognosis. Accurate diagnosis remains challenging due to variable clinical presentations, a broad histologic spectrum, and overlap with benign vascular proliferations.ObjectiveTo provide a comprehensive review of cutaneous AS, emphasizing clinical contexts, histopathologic subtypes, immunohistochemical features, molecular alterations, and key diagnostic distinctions from histologic mimics.MethodsA literature review of recent clinicopathologic, immunohistochemical, and genomic studies was performed to synthesize current diagnostic and molecular insights into primary and secondary cutaneous AS.FindingsPrimary cutaneous AS most often arises on sun-damaged skin of older adults, whereas secondary cutaneous AS develops after radiation exposure or chronic lymphedema. Cutaneous AS exhibits diverse morphologies ranging from well-differentiated vasoformative to solid or epithelioid patterns. Immunohistochemistry supports endothelial lineage (CD31, ERG, FLI1) and excludes morphologic mimics, although keratin expression represents a diagnostic pitfall. MYC amplification, detected by FISH or IHC, is a hallmark of secondary cutaneous AS and distinguishes it from benign atypical vascular lesions. Next-generation sequencing (NGS) further identifies MYC/FLT4 co-amplification, UV mutational signatures, and DNA damage response pathway alterations, providing both diagnostic and therapeutic implications.ConclusionsDiagnosis of cutaneous AS requires integration of clinical context, histopathology, and ancillary testing. MYC testing is critical for differentiating secondary cutaneous AS from post-radiation atypical vascular lesions, while NGS expands the molecular understanding of cutaneous AS. Early biopsy, adequate tissue sampling, and judicious use of IHC, FISH, and NGS improve diagnostic precision and may guide targeted or immune-based therapies.

Odontogenic myxoma is a rare, benign mesenchymal odontogenic neoplasm. Microscopically, odontogenic myxoma consists of spindle-shaped or stellate cells within an myxoid stroma. In rare tumors, the stroma contains heavy collagen deposition, and they are then termed odontogenic fibromyxomas. We report an unusual synchronous presentation of an odontogenic fibromyxoma and an osteoma in a 12-year-old boy, which clinically mimicked an ameloblastic fibro-odontoma. The patient presented with a left mandibular mass. Imaging revealed an extensive 51-mm osteolytic lesion accompanied by a hyperdense calcified mass. Radiographic findings were suggestive of an ameloblastic fibro-odontoma. A biopsy of the tumor was performed, and the calcified mass was excised. Histopathological analysis confirmed the diagnosis of an odontogenic fibromyxoma with an associated compact osteoma. The patient underwent a partial mandibular resection and remains disease-free at the 12-month follow-up. A synchronous occurrence of an odontogenic myxoma and an osteoma is rare and can mimic other lesions, making diagnosis challenging.

Mammary myofibroblastoma (MFB) is a rare benign mesenchymal tumor of the breast with myofibroblastic differentiation. Its diverse morphological spectrum may pose diagnostic challenges, particularly in limited biopsy specimens. All MFB patients diagnosed at a tertiary care center between 2015 and 2024 were reviewed retrospectively. Eleven patients were identified, including 7 women and 4 men, with a mean age of 56.5 years (range: 31-75 years). All patients presented with a solitary, painless breast mass. Tumor size ranged from 2.3 to 14 cm. Histologically, 9 tumors showed spindle cell morphology, whereas 2 showed epithelioid features. The common findings included short intersecting fascicles of bland spindle cells, variable collagen deposition, ectatic blood vessels, and focal adipocytic components. Immunohistochemically, CD34 was positive in 9 tumors, desmin in 8, smooth muscle actin (ACTA2) in 5, BCL2 and CD99 in 7 each, and CD10 in 4 tumors. Keratin AE1/AE3, p63, S100, and STAT6 were negative in all tumors. Follow-up data was available in 9 patients and no recurrence was reported. Recognition of its characteristic morphological and immunohistochemical features is essential to avoid diagnostic pitfalls. Complete surgical excision is curative, with an excellent prognosis.

ObjectiveThis study aims to conduct a comprehensive, multidimensional evaluation of how clinical and pathological factors influence invasive disease-free survival (IDFS) and cancer-specific survival (CSS) in patients with human epidermal growth factor receptor 2 (ERBB2/HER2) positive breast cancer receiving adjuvant trastuzumab therapy. Additionally, a stratified assessment will be conducted based on the hormone receptor (HR) status; thereby providing a practical basis for clinical treatment.MethodA total of 643 patients with HER2-positive breast cancer who received adjuvant trastuzumab therapy were retrospectively included. The patients' clinical and pathological information, as well as IDFS and CSS data, were systematically collected and evaluated. Survival analysis was conducted via the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression models were used to assess the effects of menstrual status, tumor size, vascular invasion, lymph node involvement, histological grade, histological type, HR status, MKI67 expression, tumor-infiltrating lymphocytes (TILs), HER2 expression, and anthracycline-based chemotherapy on IDFS and CSS. Additionally, clinicopathological characteristics of patients with HER2-positive breast cancer who received trastuzumab treatment were analyzed.ResultAmong all patients, HER2(3+), absence of lymph node metastasis, and anthracycline-based chemotherapy were independently associated with prolonged CSS. Notably, anthracycline use was an independent predictor of longer CSS in HR-negative patients. In the HR-positive subgroup, patients with HER2(3+) status demonstrated a significant CSS benefit compared to those with HER2(2+)/FISH(+) status.ConclusionHER2 expression status affects CSS in patients with HER2-positive breast cancer receiving adjuvant trastuzumab therapy. HR-negative patients may derive clinical benefit from anthracyclines, providing evidence to support anthracycline-based regimens combined with trastuzumab as the adjuvant treatment for HR-negative, HER2-positive breast cancer.

AimsTo systematically analyze the immunohistochemical expression patterns of NECTIN4 and TROP2 in breast cancer, their clinicopathological correlations, and associations with PDL1 status.Materials and methodsNECTIN4 (H-score), TROP2 (H-score), and PDL1 (Combined Positive Score, CPS) expression were evaluated in 112 surgically resected breast carcinomas using validated immunohistochemical assays. Associations with clinicopathological variables were analyzed using Spearman's correlation, χ[2] tests, and Mann-Whitney U tests.ResultsNECTIN4 exhibited moderate-to-high expression (H-score ≥ 100) in 78% of specimens, predominantly localized to the cell membrane, and showed a significant positive correlation with HER2 positivity (ρ = 0.27, P < .01). TROP2 displayed near-ubiquitous moderate-to-high expression (96%) and exhibited higher expression in the triple-negative breast cancer (TNBC) subtype. Notably, there was no significant correlation between NECTIN4 or TROP2 and PDL1 co-expression.ConclusionsThis study provides a comprehensive characterization of NECTIN4 and TROP2 expression in breast cancer, suggesting their potential as biomarkers. The observed associations with PDL1 and clinicopathological features may inform future investigations into their biological roles and clinical relevance.

The uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal tumor of the uterus. Morphological patterns can show sheets, cords, and trabeculae that are similar to those seen in ovarian sex cord-stromal tumors. Immunohistochemically, they exhibit a polyphenotypic variable pattern, including epithelial, myoid, and sex cord lineage as well as hormone receptors. We report a female patient with a UTROSCT harboring a GREB1::NCOA2 fusion that demonstrated a diffuse, strong positivity with chromogranin, synaptophysin, and CD56. INSM1 was performed to rule out true neuroendocrine differentiation. While neuroendocrine marker expression is rare in UTROSCT, this report adds to the limited literature describing this unusual immunoprofile, particularly in the context of GREB1 rearrangements. This study remains important to highlight the inclusion of this type of immunohistochemical staining in the spectrum of features UTROSCT can represent. Recent systematic review evidence suggests that GREB1-rearranged UTROSCTs may represent a biologically and clinically distinct subset from ESR1-rearranged tumors, with differences in clinicopathological features and molecular characteristics.

ObjectiveGastric-type endocervical adenocarcinoma (G-EAC) is a rare, non-HPV-associated subtype of endocervical adenocarcinoma with challenging diagnosis and poor prognosis. This study aims to characterize its clinicopathological features and evaluate the expression and prognostic significance of CLDN18.MethodsA total of 13 patients with pathologically confirmed G-EAC were collected.ResultsThe 13 patients, aged 39 to 64 years (mean 51.6 years), mostly sought medical attention due to abnormal findings on physical examination or specific symptoms, including abnormal vaginal discharge. Ten specimens were well-differentiated G-EAC, and 3 were moderately to poorly differentiated G-EAC. Atypical lobular endocervical gland hyperplasia (LEGH) was observed adjacent to G-EAC in 12 specimens. The International Federation of Gynecology and Obstetrics (FIGO) stage was stage I in 12 specimens and stage III in 1 specimen. The Ki-67 proliferation index ranged from <5% to 90%. Mutant-type immunostaining of p53 (overexpression or null pattern) was observed in 9 specimens; all 13 specimens were negative for estrogen receptor (ER), and 7 specimens showed positive CLDN18 expression. An exploratory survival analysis showed a trend toward shorter progression-free survival (PFS) in patients with positive CLDN18 expression (P = .044), a finding limited by the small sample size. Thus, CLDN18 may serve as a highly specific diagnostic adjunct in a panel, and its potential prognostic significance warrants further investigation in larger cohorts.ConclusionG-EAC is rare, and its clinical diagnosis is challenging. Clinicians should maintain a high index of suspicion, perform colposcopy with multi-site biopsy and endocervical curettage for suspicious specimens. Pathologists should integrate a panel of immunohistochemical markers with morphology to differentiate it from benign mimics. In addition, CLDN18 may not only serve as a diagnostic marker for G-EAC but may also be associated with patient prognosis, demonstrating its potential predictive value.

ObjectiveTo report a rare lesion, an intra-articular extra-synovial venous-type synovial haemangioma of the knee in a young adult and to review the relevant literature on this frequently misdiagnosed entity.Case reportA 21-year-old man presented with recurrent knee effusions and pain over several years. Imaging studies revealed a well-defined, intra-articular, extra-synovial soft-tissue mass located in the anteromedial compartment of the knee. Magnetic resonance imaging (MRI) demonstrated multiple tubular structures with high signal intensity on T2- and short tau inversion recovery (STIR)-weighted images and intense, homogeneous contrast enhancement, consistent with a vascular lesion. Surgical excision was performed, and histopathological analysis confirmed a venous-type synovial haemangioma, characterized by large-calibre vascular channels lined by bland endothelial cells and containing organizing thrombi. The postoperative course was uneventful, and the patient remained disease-free at 6 months of follow-up.ConclusionSynovial haemangioma, though rare, should be considered in the differential diagnosis of recurrent knee effusions in young patients. It may mimic other benign or malignant periarticular lesions. MRI plays a key role in the evaluation, and the diagnosis can be strongly suggested by imaging, but histopathological confirmation remains essential for accurate characterization and appropriate management.

Salivary duct carcinoma is a rare, aggressive salivary gland malignancy that morphologically and immunophenotypically resembles breast ductal carcinoma. The rhabdoid variant is characterized by discohesive tumor cells with rhabdoid cytomorphology, frequent loss of E-cadherin expression, and morphologic overlap with pleomorphic invasive lobular carcinoma of the breast. We report a 74-year-old man who presented with an enlarging right buccal mass and trismus. Positron emission tomography-computed tomography demonstrated right cervical lymphadenopathy with no evidence of breast or lung primary. Resection revealed a discohesive, infiltrative tumor composed of pleomorphic rhabdoid cells, with scattered cells containing intracytoplasmic mucin imparting a signet-ring morphology, and prominent targetoid perineural invasion. Immunohistochemically, the tumor showed diffuse positivity for keratin 7, gross cystic disease fluid protein 15 (GCDFP15/PIP), androgen receptor, weak GATA3 expression, loss of E-cadherin, and cytoplasmic p120-catenin (CTNND1) staining, a profile closely resembling that of invasive lobular carcinoma. Extensive nodal metastases were identified. Despite multimodal therapy, the disease recurred. This report highlights the importance of recognizing salivary duct carcinoma with rhabdoid features to avoid misdiagnosis and guide appropriate management.

Mixed hepatocellular carcinoma (HCC) and neuroendocrine tumor (NET) constitute an exceedingly rare and diagnostically challenging entity. We report a 70-year-old man with hepatitis C-related cirrhosis and multifocal HCCs, who was status post multiple microwave and radiofrequency ablation procedures. Total hepatectomy revealed a 1.9-cm viable tumor that, on histologic examination, showed moderately differentiated HCC with trabecular and pseudoacinar growth patterns and expression of albumin, arginase-1, and HepPar-1. Notably, a neuroendocrine component comprising ∼20% of the tumor volume was identified. This component consisted of sheets of intermediate-sized cells with inconspicuous nucleoli and scant cytoplasm. Scattered tumor cells with enlarged nuclei were present, but mitotic figures were difficult to identify, and no necrosis was observed. Immunohistochemically, these tumor cells were positive for synaptophysin and negative for hepatocellular markers, with wild-type p53, retained nuclear RB1, and patchy SSTR2A expression. The Ki-67 labeling index was heterogeneous, ranging from 5% in low-proliferation areas to 31% in hotspots, with an average of 11%. The morphologic and immunohistochemical findings supported a diagnosis of mixed HCC and grade 3 (high-grade) well-differentiated NET. This diagnosis should be distinguished from mixed HCC and neuroendocrine carcinoma given important differences in therapeutic decision-making and prognostic assessment.

BackgroundCytomegalovirus (CMV) hepatitis after liver transplantation may mimic or coexist with acute T-cell-mediated rejection (TCMR), complicating treatment decisions. We sought practical histologic features favoring CMV hepatitis in liver allograft biopsies with overlapping rejection-type changes.MethodsWe retrospectively studied 12 patients with CMV hepatitis and 12 CMV immunohistochemistry-negative acute TCMR controls. CMV hepatitis required viral cytopathic inclusions on hematoxylin and eosin sections at the index biopsy. Two liver pathologists, including one blinded reviewer, re-reviewed hematoxylin and eosin sections; discrepancies were resolved by consensus. C4d immunohistochemistry was performed on all index biopsies and reviewed descriptively. One CMV biopsy was excluded from comparative histologic analysis because the deeper study level was unreliable, leaving 11 CMV and 12 TCMR biopsies.ResultsClinical and transplant characteristics were similar between groups. Plasma CMV DNA was detected in all tested CMV patients and absent in tested TCMR controls. Definite concurrent acute TCMR was diagnosed in 2 of 12 CMV biopsies, while 9 were indeterminate or not evaluable for TCMR. CMV hepatitis more often showed microgranulomas (7/11 vs 1/12; P = .009) and neutrophilic microabscesses (4/11 vs 0/12; P = .037). Bile duct injury was less frequent in CMV hepatitis (7/11 vs 12/12; P = .037) and was usually mild and patchy when present. Venous endotheliitis was common in both groups.ConclusionsMicrogranulomas, neutrophilic microabscesses, and less frequent, usually mild bile duct injury favor CMV hepatitis. These findings do not exclude concurrent TCMR but should prompt careful search for viral inclusions, a low threshold for CMV immunohistochemistry, and close clinicopathologic correlation.

NTRK-rearranged spindle cell neoplasm is a rare lesion in the uterus (including the cervix), with more than 60 tumors reported in the literature so far. Most of them are characterized by fascicles of spindle cells in herringbone pattern with entrapment of endocervical glands. We report an additional tumor occurring in the uterine cervix of a 43-year-old Chinese woman, which demonstrated unusual morphologic features in addition to the conventional fibrosarcoma-like spindle cell proliferation. These included areas of neural-like whorls, as well as nuclear palisading that resembled a schwannoma. Focal myxoid stroma with loose clusters of rhabdoid cells was also identified. The nuclear grade was intermediate to severe and geographic necrosis was identified. Immunohistochemistry showed diffuse positivity for pan-TRK with patchy CD34 and focal S100 expression. Molecular analysis revealed the presence of TPM3::NTRK1 fusion with CDKN2A/B homozygous deletion and low mutational burden. Our case report and literature review highlight the diverse morphological appearance of this tumor. Specifically, nuclear palisading and rhabdoid cells are rarely reported in uterine NTRK-rearranged spindle cell neoplasm. As more clinical and molecular data become available, the clinicopathological features of this entity can be further characterized.

Phaeohyphomycosis is an uncommon fungal infection caused by dematiaceous (melanized) fungi, typically presenting as a localized subcutaneous nodule or cyst, and as systemic disease in immunocompromised individuals. It rarely involves the gastrointestinal tract. Esophageal candidiasis, a common fungal infection of the gastrointestinal tract, may cause dysphagia, whereas giardiasis is a protozoal infection, primarily associated with diarrhea and malabsorption. We report an unusual example of concomitant esophageal and gastric phaeohyphomycosis, esophageal candidiasis and duodenal giardiasis in an 8-year-old child, who presented with absolute dysphagia secondary to esophageal stricture and severe malnutrition. Histopathological examination established the diagnosis, and the patient was successfully managed with medical therapy, resulting in complete clinical, endoscopic, and histological resolution on follow-up.

BackgroundUlcerative Colitis (UC) is a chronic inflammatory bowel disease affecting the colonic mucosa, with a relapsing-remitting course. Disease activity is assessed using clinical, serologic, endoscopic, and histological parameters, among which the latter two remain the cornerstone for assessing disease severity and therapeutic response. However, limited studies have evaluated the correlation between endoscopic and histological activity. This study evaluates the correlation between the Mayo endoscopic score (MES) and validated histological indices, namely the Geboes score (GS), Nancy index (NI), and Robarts histological index (RHI), to determine the most practical and reliable histological scoring system.MethodsThis cross-sectional study was conducted over a period of two and a half years at a tertiary care hospital in North India and included 146 established UC patients. Colonoscopic evaluation was performed by a single gastroenterologist, and biopsies were obtained from areas showing the highest possible MES. Subsequent histopathological examination and scoring using the histological indices (GS, NI, and RHI) were performed independently by pathologists masked to the endoscopic findings. Correlations were assessed using the Chi-Square test and Spearman's rho to evaluate relationships between endoscopic and histopathological scores.ResultsA total of 146 biopsies were analyzed, with a median patient age of 34 years; male patients constituted 56% of patients, and the recto-sigmoid region was the most commonly affected site (62%). Moderate (50%) and severe (32%) endoscopic aspects suggestive of UC activity were predominant. Correlation coefficients between MES and GS/RHI/NI were moderate (rho = .617/.622/.599, respectively; P < .001 for all three correlations). The NI was the fastest to evaluate and demonstrated a similar correlation with the MES compared to the GS and RHI.ConclusionA moderate yet consistent correlation was observed between the MES and all three histopathological indices, highlighting their reliability in reflecting disease severity and supporting their interchangeable use in routine practice. Among them, the NI emerged as the most practical and user-friendly scoring system due to its simplicity and rapid applicability, while maintaining diagnostic performance comparable to the GS and RHI.