Context Intimal sarcoma is a rare, aggressive malignant mesenchymal neoplasm arising from large vessels and the heart. Pulmonary artery involvement frequently mimics chronic thromboembolic pulmonary hypertension (CTEPH), resulting in delayed diagnosis and poor outcomes. Cases We report two cases of pulmonary artery intimal sarcoma (PAIS) identified in patients undergoing pulmonary endarterectomy for presumed CTEPH. Both patients presented with clinical and radiographic features consistent with chronic thromboembolic disease. Histologic examination of endarterectomy and tumor specimens revealed high-grade sarcomas with predominantly intraluminal growth, marked cytological atypia, and extensive necrosis. Immunohistochemical studies demonstrated limited lineage-specific differentiation, with focal expression of vascular and smooth muscle markers and broad negativity for epithelial, hemato-lymphoid, and melanocytic markers. In both cases, fluorescence in situ hybridization (FISH) demonstrated high-level MDM2 amplification, confirming the diagnosis of intimal sarcoma. Results Despite surgical intervention, both patients experienced rapid postoperative deterioration and died shortly after diagnosis. Conclusion PAIS is an important, but under-recognized mimic of CTEPH. Careful histologic evaluation of pulmonary endarterectomy specimens and consideration of MDM2 FISH testing in atypical cases are critical for accurate diagnosis. These cases underscore the aggressive nature of this entity and the need for heightened pathologic suspicion when thromboembolic disease behaves atypically.
Cystic adenomyoma is a rare focal variant of adenomyosis characterized by a cystic cavity lined by endometrial glands and stroma within hypertrophic smooth muscle. Subserosal pedunculated forms are exceptionally uncommon and may mimic uterine or adnexal masses, leading to diagnostic challenges. We report a case of a 28-year-old nulliparous woman presenting with severe progressive dysmenorrhea refractory to medical therapy since adolescence. Her medical history was notable for a previous right salpingo-oophorectomy performed ten years earlier. Pelvic ultrasound demonstrated a well-defined 6-cm cystic lesion arising from the uterine wall via a subserosal stalk, without communication with the endometrial cavity. Diagnostic laparoscopy identified a pedunculated mass originating from the uterine serosal surface, which was completely excised. Gross examination revealed an encapsulated cystic lesion containing hemorrhagic fluid. Histopathological analysis showed interlacing smooth muscle bundles with embedded endometrial glands and stroma, confirming cystic adenomyoma. The patient experienced complete resolution of symptoms with normal menstrual cycles at 4-month follow-up. This case illustrates an exceedingly rare pedunculated subserosal cystic adenomyoma manifesting as severe dysmenorrhea. Recognition of this entity is important in young women with persistent menstrual pain and normal uterine cavity morphology. Accurate diagnosis relies on imaging correlation, surgical evaluation, and histopathological confirmation, while laparoscopic excision remains as a treatment of choice.
Collision tumors with squamous cell carcinoma (SCC) and malignant melanoma components are extremely rare. We report a case of a penile collision tumor with a component of HPV-associated SCC and malignant melanoma in a 61 year-old man. The patient underwent a partial penectomy and bilateral inguinal sentinel lymph node surgery. Microscopy showed a biphasic tumor with a component of SCC with warty-basaloid morphology, positive for HPV16 and 43, and a malignant melanoma associated with a BRAF mutation. This case posed diagnostic and therapeutic challenges due to the absence of a precise TNM classification and documented treatment guidelines for this tumor type.
Background In cases where tumors share histological and immunohistochemical features, molecular studies can assist in achieving a definitive diagnosis. Next generation sequencing (NGS)-based molecular profiling helps identify characteristic genetic alterations associated with specific cancer types and mutational signatures such as tumor mutational burden (TMB). Gene fusions, present in approximately 30–50% of sarcoma cases, are especially valuable for distinguishing sarcoma from other solid tumors. However, atypical rearrangements in promiscuous genes such as EWSR1 may complicate interpretation. Case description Here we present the molecular workup of a gastrointestinal mass with a differential diagnosis of clear cell sarcoma or melanoma using DNA- and RNA-based solid tumor NGS panels and fluorescence in situ hybridization (FISH). No EWSR1::ATF1 or EWSR1::CREB1 fusions were identified by NGS; however, EWSR1 copy number gain and atypical EWSR1 fusion events were detected, representing potential diagnostic pitfalls. A high TMB (99.3 muts/Mb) and pathogenic somatic variants in BRAF, NF1 and TP53 ultimately supported a diagnosis of melanoma. Conclusions In the context of complex genomic architecture and atypical EWSR1 rearrangements, where single assays may fail to detect unusual but diagnostically critical alterations, integrating DNA-based NGS with an RNA-based fusion panel yields a more reliable molecular profile. The identification of a high TMB and multiple established somatic mutations ultimately facilitated the diagnosis of melanoma over clear cell sarcoma, despite overlapping histological and immunohistochemical features.
Introduction Undifferentiated spindle cell sarcomas (USCSs) of the breast are extremely rare, and their metastasis to the mandible and vertebrae is even rarer. This report presents a case of breast USCS metastasized into the mandible and vertebrae. Case presentation A 45-year-old woman presented with a rapidly growing, firm, non-tender left breast mass. Core biopsy confirmed high-grade USCS (Grade III). She underwent wide local excision with sentinel lymph node biopsy, which showed a 5.8 cm tumor (pT2N0) with high mitotic index, extensive necrosis, and negative margins. Nine months later, she developed lower lip numbness, and contrast-enhanced computed tomography revealed a mandibular lesion along the inferior alveolar nerve. Biopsy confirmed the lesion as metastatic sarcoma. Three weeks later, severe back pain led to magnetic resonance imaging detection of vertebral metastases (T12- L2), which were confirmed histologically. She was put on palliative chemotherapy, bisphosphonates, and neuropathic pain management, with stable disease at 4 months post-diagnosis of metastasis. Literature review Nine cases of primary and metastatic oral cancer were reviewed, of which seven cases were females. Pain and swelling were the most common symptoms. Among the five cases with metastasis, in four of them, the primary cancer originated from the breast. Treatments varied, including surgical approaches, chemotherapy, hormone therapy, and radiotherapy, and two patients died. Conclusion Breast USCS is a rare sarcoma that might metastasize to the mandible and vertebrae. Breast-wide local excision and radiotherapy may reduce the risk of local recurrence; however, distant metastasis may still occur.
Background Ectopic breast tissue (EBT) is an embryological anomaly occurring in 0.4–6% of the population due to incomplete regression of the mammary ridge. While frequently asymptomatic, EBT can harbor the same pathologies as orthotopic breast tissue. This review addresses the “diagnostic conundrum” of axillary EBT, which is often misidentified as lymphadenopathy, especially in regions with a high burden of tuberculosis. Methods We present an illustrative case of an axillary fibroadenoma in a 23-year-old female with a history of cervical tuberculosis, alongside a systematic review of cases from the literature to evaluate diagnostic pathways and clinical outcomes. Case Presentation A 23-year-old female presented with a persistent, non-tender right axillary mass. Given her history of treated cervical tuberculous lymphadenopathy, initial suspicion favored nodal pathology. Ultrasonography revealed a heterogeneous hypoechoic lesion. Following the proposed diagnostic algorithm, an FNAC suggested fibroadenoma, and surgical excision was performed. Histopathology confirmed a fibroadenoma arising within ectopic breast tissue. Discussion Modern anatomical evidence challenges the traditional “Axillary Tail of Spence” theory, favoring the concept of isolated segmental primordia along the milk line. Our review highlights that while USG and FNAC are primary tools, dynamic contrast-enhanced MRI serves as a crucial adjunct for inconclusive cases. The “TB distractor” remains a significant cause of misdiagnosis in endemic areas. Conclusions Fibroadenoma in axillary EBT must be included in the differential diagnosis of axillary swellings in reproductive-age women. A structured diagnostic approach, moving from USG to FNAC and, if necessary, MRI ensures accurate diagnosis and prevents inappropriate treatment.
Angiomatoid fibrous histiocytoma (AFH) is a rare, low-grade soft tissue neoplasm which typically occurs in the deep dermis or subcutis of extremities in children and young adults. We report an unusual case of an 8-year-old boy who presented with progressive exertional dyspnea and fatigue, and was found to have a 4 cm mass in the right atrium. The patient underwent surgical resection. Histologic examination revealed sheets of medium-sized neoplastic cells, with scant cytoplasm, finely stippled chromatin and inconspicuous nucleoli in addition to pseudoangiomatous spaces, and a background of lymphocyte-predominant chronic inflammation. Fluorescence in situ hybridization (FISH) demonstrated EWSR1 gene rearrangement and subsequent Next Generation Sequencing (NGS) identified a EWSR1::ATF1 fusion, confirming the diagnosis of Angiomatoid Fibrous Histiocytoma (AFH). To our knowledge, this represents a previously unreported cardiac location for AFH and highlights the importance of keeping it under diagnostic consideration even in highly unusual sites.
Purpose: To present two cases of ocular toxoplasmosis diagnosed by histopathological examination of eviscerated eyes. Observations: Ocular toxoplasmosis is primarily a clinical diagnosis, however atypical presentations and limitations in serological and molecular testing make the diagnosis challenging. We report two patients who were infected by the parasite Toxoplasma gondii and underwent evisceration of their blind eye. Histopathological analysis of the intraocular contents in each case demonstrated retinal necrosis located above and below the retinal pigment epithelium (RPE), identification of tachyzoites and bradyzoites, and confirmatory immunohistochemical method for Toxoplasma gondii using monoclonal antibodies. These findings are similar to previously described histopathological criteria in enucleated eyes with ocular toxoplasmosis. Conclusion and importance: This is the first report demonstrating histopathological diagnosis of ocular toxoplasmosis using evisceration rather than enucleation in immunocompromised patients. These findings support consideration of evisceration as an alternative to enucleation and highlight three key histopathological features essential for diagnosis.
Glomus tumors are mesenchymal neoplasms arising from anastomotic glomus bodies, primarily occurring in the extremities. While glomus tumors have been reported in various extracutaneous locations, tracheal involvement is exceedingly rare, with fewer than 80 documented cases. Due to their nonspecific clinical presentation and radiologic overlap with more common tracheal neoplasms, tracheal glomus tumors are frequently misdiagnosed. We present a case of a 40-year-old male presenting with chronic hemoptysis, determined by tissue sampling to be a primary tracheal glomus tumor. This case highlights the diagnostic challenges associated with tracheal glomus tumors and underscores the importance of considering rare neoplasms in the evaluation of unexplained airway obstruction as early recognition and appropriate management are crucial for optimizing patient outcomes.
Information on lymphatic vessels in human endometrium is unsettled. We planned to study immunocytochemical presence of the elusive lymphatic vessels in the eutopic human endometrium with frozen sections. By immunostaining lymphatic vessels from eutopic human endometrium, we studied lymphatic vessels and blood vessels in the post-menstrual, proliferative, secretary and menstrual stages. We used D2-40 and LYVE-1 as lymphatic vessels markers as compared to von Willebrand factor as a blood vessel marker. There was consistent presence of lymphatic vessels in myometrium and basalis. Blood vessels supply the repairing functionals while lymphatic vessels grew longitudinally from basalis to deep functionalis during proliferative phase and further grew from lower to the middle to upper secretary functionalis in late secretary phase. Thus, lymphatic vessels grew from the basalis after menstruation and grew to entire functionalis in the late secretary phase. In the late secretary menstrual phase, D2-40 immunostained larger but less lymphatic vessels in deep functionalis while LYVE-1 immunostained smaller but more lymphatic vessels in the entire functionalis. We concluded that ample blood vessels supplied the entire repair endometrium while lymphatic vessels did not catch up with the fast-growing blood vessels in the functionalis. D2-40 immunostains less but larger lymphatic vessels while LYVE-1 immunostains small but more lymphatic vessels. The less lymphatic vessels in the late secretary phase may contribute to interstitial endometrial edema during menstrual shedding. The presence of lymphatic vessels in the endometrium during the menstrual period implies the presence of sliver of lymphatic fluid in the menstrual fluid.
X-linked agammaglobulinemia (XLA) is among the most frequent primary immunodeficiencies in childhood. This disorder is caused by a disruption in B cell development resulted from mutations in Bruton’s tyrosine kinase (BTK) gene. We used whole exome sequencing (WES) to find the underlying genetic basis of immunodeficiency in a group of patients with different clinical manifestations and reported 10 cases of XLA. A range of different mutation types, including nonsense (e.g., p.Gln234*), missense (e.g., p.Arg615Ser), and frameshift (e.g., p.Glu271Lysfs*6) mutations, as well as one splice site variant (c.1631 + 5G > T in Case 8) were detected in the patients. This study provides an overview of BTK variants among Iranian patients and shows the heterogeneous pattern of these variants. Based on the importance of early diagnosis and identification of genetic basis of immunodeficiency in the affected individuals, we suggest early application of WES in the course of molecular diagnosis to save time and cost.
Adenomatoid tumor is a rare benign neoplasm that arises from mesothelial cells. It is commonly found in the genital tract, and the adrenal gland is an is an extremely rare location for adenomatoid tumor. Herein we report a rare case of adrenal adenomatoid tumor in an 83-year-old man with a history of lung non-small cell carcinoma. CT scan of the abdomen revealed a 2.2 x 1.5 cm nodular lesion in the left adrenal gland. Subsequent biopsy of the adrenal lesion revealed extensive tubular-like and vascular like spaces, which were lined with flat or cuboidal cells. The tumor cells showed minimal cytologic atypia with low proliferative activity. Immunohistochemically, the tumor cells were positive for pancytokeratin, calretinin, WT-1, D2-40, and CK7; and negative for TTF-1, SOX10, HMB45, SF1, ERG, and CD31. The overall features are consistent with adenomatoid tumor. We also reviewed adrenal adenomatoid tumors that have been reported in the English literature and identified the morphological and immunohistochemical characteristics that can be used to distinguish adenomatoid tumor from its mimickers in the adrenal gland.
The 2019 World Health Organization Classification of Digestive Tumors recognizes undifferentiated rhabdoid tumors, driven by switch/sucrose non-fermentable (SWI/SNF) chromatin-remodeling complex alterations such as SMARCA4, SMARCA2, SMARCB1, and ARID1A under the undifferentiated carcinoma category. SMARCA4-mutated undifferentiated tumors, first described in thoracic sites, are increasingly recognized in extrathoracic locations including the gastrointestinal tract. These tumors are high-grade epithelial neoplasms characterized by loss of differentiation and SMARCA4 expression. We report a 53-year-old woman presenting with severe anemia secondary to heavy vaginal bleeding. Imaging revealed a large ileal mass with hepatic hypodensities. She underwent ileocolic and hepatic wedge resections and hysterectomy. Histopathology revealed two separate tumors: a low-grade, mismatch repair (MMR) intact endometrioid endometrial carcinoma and a SMARCA4-mutated undifferentiated ileal neoplasm with epithelioid/rhabdoid morphology and liver metastasis. The ileal tumor was positive for vimentin and showed p53 overexpression with preserved SMARCB1 expression. It displayed microsatellite instability (MSI). Next-generation sequencing detected loss-of-function variants in SMARCA4 and ARID1A. The endometrial carcinoma differed in morphology and MMR status, supporting two independent primaries. SMARCA4-mutated undifferentiated tumor of the small intestine is exceedingly rare. To our knowledge, concurrent SMARCA4 and ARID1A mutations with MSI have not been documented in a primary ileal tumor. This case underscores the diagnostic challenges of SWI/SNF-mutated tumors, particularly in distinguishing synchronous primaries from metastatic carcinoma with rhabdoid tumor-like evolution. SWI/SNF assessment in undifferentiated small bowel tumors, especially with rhabdoid morphology, is warranted. Future studies should explore predictive value for immunotherapy and targeted approaches in MSI-high, ARID1A-deficient tumors.
Approximately 30% of patients with ulcerative colitis (UC) who achieve endoscopic and histologic remission after biologic therapy continue to report persistent irritable bowel syndrome (IBS)-like lower gastrointestinal symptoms. We hypothesized that mucosal mast cells, which have been implicated in IBS pathophysiology, might play a role. We conducted a retrospective case-control study using systematic random sampling of cases from an institutional database. UC patients with a Mayo endoscopic score of 0 and absent mucosal neutrophils were identified through a consecutive review of electronic medical records in chronological order. Symptom status was determined by contemporaneous clinical documentation within two weeks of colonoscopy. The first twelve symptomatic patients meeting all eligibility criteria were matched by age, sex, disease duration, and therapy to twelve asymptomatic controls. Ninety-six colonic biopsies were reviewed histologically and stained for CD117 to quantify mast cell density. Mucosal mast cell density was significantly higher in symptomatic patients compared with asymptomatic controls (54.9 +/- 11.5 vs. 40.2 +/- 13.2 cells per high-power field; P = 0.0007). It was observed consistently across colonic segments and was uncorrelated with duration of remission (range, 0-208 months). Receiver operating characteristic analysis demonstrated good discrimination between symptomatic and asymptomatic patients (AUC = 0.875). Pancolonic mucosal mast cell density is associated with persistent IBS-like symptoms in UC patients who achieved endoscopic and histologic remission, suggesting a durable potential target for IBS-like symptom-directed therapy.
Fibroadenomas are the most common benign breast tumors in young women, typically arising in the second and third decades of life. They are hormone-sensitive and may enlarge rapidly during pregnancy and lactation, occasionally presenting as giant fibroadenomas. Infarction within fibroadenomas is a rare event, but when it occurs, it may resemble necrotic carcinoma both clinically and microscopically. We report the case of a 38-year-old female who presented with a rapidly enlarging right breast mass that increased markedly in size following delivery. Careful evaluation, with the patient’s history, imaging, and histopathology, was required for accurate diagnosis. Awareness of the possibility of infarction within fibroadenomas is crucial for physicians and pathologists to avoid misdiagnosis with carcinoma, like Pregnancy-associated breast cancer (PABC). Early recognition and timely excision are essential in managing such cases, particularly in pregnancy and lactation.
We report a case of membranoproliferative glomerulonephritis (MPGN) with dominant C3 and uniquely organized deposits complicated by pulmonary non-tuberculous mycobacterial (NTM) infection. A 64-year-old man developed persistent urinary abnormalities following treatment with Mycobacterium malmoense. A renal biopsy revealed MPGN with characteristic fibrous organized deposits and strong complement C3c and fibrinogen positivity, but IgG, IgA, IgM, and C1q negativity. Immunosuppressive therapy was not administered. The patient’s renal function gradually declined, but subsequently stabilized with prolonged antibiotic therapy. This case highlights the importance of considering infection-related glomerulonephritis with C3-dominant organized deposits, particularly in the absence of any immunoglobulin involvement, as well as the need to distinguish this entity from primary C3 glomerulopathy.
Large cell neuroendocrine carcinoma (LCNEC) of the breast (LCNECB) is exceedingly rare. We encountered a case of combined LCNEC, invasive breast carcinoma of no special type (IBC-NST), and squamous cell carcinoma (SCC) of the breast. The tumor was initially diagnosed on biopsy as high-grade triple-negative breast carcinoma (TNBC). The surgical specimen after neoadjuvant chemo-immunotherapy showed no residual TNBC but revealed ductal carcinoma in situ and luminal type A-like IBC-NST. Based on these findings, anti-estrogen therapy and radiotherapy were initiated. However, brain metastasis developed seven months after mastectomy. After morphological and immunohistochemical comparison among the biopsy, mastectomy, and brain specimens, the final diagnosis was combined LCNEC with IBC-NST and SCC. Although the diagnosis of LCNECB can often be challenging, accurate histologic identification is essential for selecting the optimal treatment strategy of breast carcinoma. No established therapeutic regimen exists for LCNECB because of its extreme rarity and overlapping histologic features with high-grade IBC-NST and neuroendocrine tumor (NET) of the breast. We discuss non-morphological diagnostic features of LCNECB that may aid in recognizing LCNECB, and review selected cases from the literature to summarize its clinicopathological characteristics and current treatment modalities for this rare tumor.
Background Renal cell carcinoma (RCC) is a heterogeneous malignancy with variable clinical behaviour. Ki-67, a nuclear antigen associated with cellular proliferation, has been investigated for its prognostic relevance in RCC. However, its utility in predicting metastatic potential remains controversial, particularly in the Indian population. This study aimed to evaluate Ki-67 expression in RCC and its association with clinicopathological features and metastatic risk. Methods A retrospective analysis of 95 RCC cases was performed at a tertiary care centre between January 2018 and December 2020. Clinicopathological data were retrieved from electronic records, and histological slides were reviewed. Ki-67 immunohistochemistry was performed on tissue microarray (TMA) sections using MIB-1 antibody. The labelling index was calculated, and cases were categorized into low (<= 10%) and high (>10%) Ki-67 expression groups. Statistical analysis included chi-square tests, Mann-Whitney U tests, Kruskal-Wallis tests, logistic regression, ROC curve analysis, and Kaplan-Meier survival analysis using SPSS v27. Results The mean age was 57.09 years; 62.1% were males. Clear cell RCC was the predominant subtype (82.1%). Ki-67 expression was low in 86.3% and high in 13.7% of cases. A higher ISUP grade was significantly associated with increased Ki-67 expression (p = 0.002), and sarcomatoid differentiation correlated with high Ki-67 expression in univariate analysis (OR = 24.3, p = 0.008). However, Ki-67 was not significantly associated with tumour size, stage, or histologic subtype. Metastasis occurred in 13.7% of cases but was not significantly associated with Ki-67 expression (p = 0.49; AUC = 0.438). Event-free survival did not differ significantly between the low and high Ki-67 groups (p = 0.71). Conclusions Ki-67 showed a significant association with tumour grade and dedifferentiation in RCC, reflecting increased proliferative activity in biologically aggressive tumours. However, Ki-67 lacks independent prognostic value for metastasis or event-free survival, suggesting that Ki-67 should be integrated into a broader multiparametric model rather than used in isolation.
For the first time, the coincidence of follicular cholangitis and hepatic Langerhans cell histiocytosis are described. Hemihepatectomy was performed for suspected malignant stenosis of the left hepatic duct. Histological examination revealed (a) massive intra- and subepithelial proliferations of CD1a- and Langerin-positive Langerhans cells (LC) (b) associated with chronic fibrosing and prominent follicular cholangitis of septal and segmental bile ducts, (c) followed by multifocal LCH with granulomatous or eosinophil-rich bile duct destruction and necrotizing obliteration of the left hepatic duct, and (d) advanced secondary biliary fibrosis originating from peripheral portal fields as a result of bile duct obliteration. The striking colocalization of these findings presume a local antigen activation of LC, as part of the innate immune system, followed by a chronic fibrosing cholangitis with a prominent periductal lymphofollicular reaction. Furthermore, proliferating LC appeared to be the source of a multifocal bile duct-associated LCH with obliteration of the left hepatic bile duct. The absence of systemic foci over the course of a year indicates LCH of hepatic origin, confined to the liver. Cases of rare, eye-catching follicular cholangitis should be analyzed more closely for reactive LC proliferations and possible hepatic LCH.
Objective: Papillary immature metaplasia (PIM) of the uterine cervix is an uncommon low-grade exophytic papillary squamous intraepithelial lesion characterized by immature metaplastic morphology. It typically involves the proximal transformation zone, often extending into the endocervical canal, and has been reported almost exclusively in premenopausal women. PIM is poorly recognized, partly because it is not included as a distinct entity in the current WHO classification of tumors. Because of its proximal location, papillary architecture, and morphologic immaturity, PIM can pose significant diagnostic challenges, particularly in postmenopausal patients. Methods: Three cases of PIM occurring in postmenopausal women were described, and a review of the literature was performed. Key findings: All three cases showed typical histopathologic features of PIM; notably, two patients presented with postmenopausal bleeding and underwent repeated endometrial sampling. Among these three cases, only one case tested positive for low-risk HPV infection based on the available testing panels. Immunohistochemically, all three lesions showed diffuse GATA3 expression, suggesting its potential utility as an adjunctive marker for PIM. Review of literature shows it occurs almost exclusively in premenopausal women presenting with abnormal screening cytology or a cervical mass. Most cases (77%) are associated with low-risk HPV, predominantly types 6 and 11, and demonstrate a low Ki-67 proliferation index. Conclusion: PIM is a poorly recognized, low-grade papillary proliferative lesion of the uterine cervix associated with low-risk HPV infection. We report three cases of PIM in postmenopausal patients to increase awareness and improve recognition of this entity, thereby helping prevent both overdiagnosis and underdiagnosis.
