Background:Heme synthesis is critical for several biological processes, including mitochondrial energy production and oxygen delivery via hemoglobin. The initial and rate-limiting step in heme synthesis is the conjugation of glycine with succinyl-CoA to form 5-aminolevulinic acid (ALA), which is catalyzed by two closely related enzymes that are coded by highly homologous genes, known as ALAS1 and ALAS2. Loss-of-function variants in ALAS2 result in sideroblastic anemia, whereas gain-of-function variants result in porphyria. We present a case of a woman who died with severe metabolic acidosis and was found to have a rare variant in ALAS2. We propose the hypothesis that the ALAS2 variant, in conjunction with other factors, was responsible for her demise. Case Report:A previously healthy 34-year-old woman presented to the emergency department of her local hospital complaining of severe fatigue. Her arterial pH was 6.95. No cause for her acidosis could be identified, and she expired from unremitting acidosis. The autopsy was notable for an enlarged liver. Whole exome sequencing identified a rare, paternally inherited variant in ALAS2. This prompted a re-evaluation of the autopsy and the development of a novel hypothesis to explain her acidosis. We propose that the ALAS2 variant identified in this family, NM_000032.5(ALAS2)c.1273C>T(p.Pro425Ser), is a conditional allele that can contribute to mitochondrial dysfunction under unusual conditions. Discussion:We hypothesize that the P425S variant identified in ALAS2 leads to dysfunction of the homeostatic down-regulation of ALAS2 in times of cofactor deficiency. This case illustrates that DNA sequencing as a part of the autopsy procedure will, as it becomes more routine, lead to the identification of sequence variants that may or may not be clinically relevant. The pursuit of hypotheses, prompted by genetic data, has the potential to identify novel pathogenic mechanisms.
Background:The prevalence of pancreatic cancer is increasing globally, with over 510,566 new cases reported in the literature in 2022. Adenosquamous carcinoma of the pancreas is a rare histological variant with poor prognosis compared to other exocrine pancreatic cancer subtypes. Little is known about the prevalence of PASC in sub-Saharan Africa. Case Presentation:Two cases are presented here: Case 1 reports PASC with invasion of the gallbladder and duodenum, and Case 2 shows early-onset PASC at an even younger age. Diagnosis was made through clinical evaluation and imaging and confirmed by histological findings. Conclusion:Due to its similar presentation with pancreatic adenocarcinoma, lack of routine immunohistochemistry in some cases, and limited access to some cross-sectional imaging, PASC is often misdiagnosed or detected late. These two cases, one with invasion of the duodenum and gallbladder and the other with atypical presentation and hepatic metastasis, highlight the need for a high clinical suspicion and histopathological confirmation in sub-Saharan Africa.
Teratoma is a germ cell neoplasm of the ovary. There are two main types of teratomas: mature teratoma and immature teratoma. Teratomas can rarely be associated with disseminated deposits. It is most commonly seen in immature teratomas. Mature teratomas with deposits are exceedingly rare. Glial tissue is the most widely implanted tissue in the case of teratomas. We report a case of immature teratoma of the ovary, postneoadjuvant chemotherapy with abdominal pain and distension. Imaging revealed an ovarian mass. Following this, total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. The patient was diagnosed with bilateral mature teratoma with disseminated deposits and ascitic fluid involvement. These deposits comprised elements with derivatives of all three germ cell layers. This case will help to shed light on the literature regarding the status of disseminated deposits and ascitic fluid involvement in mature teratoma of the ovary.
Among 86 adult patients who underwent surgery for intestinal perforation, excluding cases caused by cancer invasion or appendicitis, diverticulitis (33/86, 38%) was identified as the most common cause of perforation, followed by ischaemia (7/86, 8%) and segmental absence of intestinal musculature (SAIM) (5/86, 6%). In patients with SAIM-related perforation, the site of perforation was the sigmoid colon in four cases and the caecum in one. SAIM-related perforation occurred predominantly in older women and most frequently involved the sigmoid colon. The four patients with sigmoid colon perforation showed an abrupt loss of the muscularis propria. In the patient with caecal perforation, the muscularis propria exhibited separation and thinning with focal complete loss. Secondary inflammation or haemorrhage associated with the perforation was observed in the bowel wall surrounding the perforation site. However, there was no evidence of primary suppurative inflammation or necrosis causing of perforation. Given that the prevalence of SAIM among patients with bowel perforation appeared to be higher than previously assumed, it is essential to histologically examine sufficient tissue samples to avoid missing this diagnosis. Recognition of SAIM is clinically important, especially in adults without previous or current evidence of intestinal disease, as it should be considered a possible cause of intestinal perforation, thereby facilitating early diagnosis and prompt treatment.
Background:Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are uncommon uterine neoplasms representing 1%-2% of uterine smooth muscle tumors. Recurrence after hysterectomy in postmenopausal patients has rarely been reported. Molecular alterations associated with recurrence remain poorly characterized. Methylthioadenosine phosphorylase (MTAP) deficiency has been described in sarcomas, but its role in STUMP remains poorly characterized. Case Presentation:A 61-year-old postmenopausal woman developed multifocal extrauterine recurrence affecting the rectus abdominis, vaginal cuff, peritoneum, small bowel, and abdominal wall 18 months after total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO) for presumed leiomyomas. The cumulative clinicopathologic findings were considered most consistent with recurrent STUMP, with one lesion exhibiting loss of MTAP expression. Retrospective review of the original hysterectomy specimen revealed previously unrecognized STUMP features, highlighting the diagnostic challenges at initial presentation. Conclusion:This case presents an unusual multifocal recurrence of STUMP following hysterectomy in a postmenopausal patient and reinforces the importance of long-term surveillance, even after definitive surgical management. Focal MTAP loss was identified in one recurrent lesion and should be interpreted cautiously as a descriptive, hypothesis-generating finding.
Low-grade oncocytic tumor (LOT) of the kidney is a rare, indolent neoplasm within the spectrum of eosinophilic renal tumors. It typically presents as a small, solitary mass and is associated with molecular alterations in TSC1, TSC2, or MTOR. We describe a 72-year-old male with a history of pancreatic neuroendocrine tumor, gastrointestinal stromal tumor, and prostate cancer who presented with multiple bilateral renal masses. Partial nephrectomy revealed two distinct tumors: one consistent with LOT and the other with a sclerosing angiomyolipoma (AML). The LOT consisted of oncocytic cells with round to oval nuclei and delicate perinuclear halos, arranged predominantly in solid architecture, and immunoreactive for PAX8, EMA, and CK7, whereas negative for CD117 and AMACR. The AML was composed of spindle and epithelioid cells embedded in sclerotic stroma, positive for MiTF and SMA, and negative for conventional melanocytic markers, including HMB45 and Melan-A. Germline testing identified a TSC1 intron 6, c.509-15G > A variant of uncertain significance. Somatic analysis showed increased allelic imbalance at the TSC1 locus, suggesting loss of heterozygosity and a potential pathogenic role. This case adds to the limited reports of multifocal LOT and demonstrates the consistent association of germline TSC1 alterations with this rare tumor presentation.
Perivascular epithelioid cell tumors (PEComa) are a family of tumors characterized by epithelioid cells and are often found in perivascular spaces. Cases originating in the lungs are highly uncommon. We discuss the case of a pulmonary PEComa found in a 71-year-old male who had two instances of lung cancer 4 years prior. He had received a left lower lobectomy and a subsequent right upper lobectomy for separate primary Stage IA adenocarcinomas. His most recent surveillance imaging revealed a cystic lesion in the left upper lobe. A surgical course of treatment was recommended, and a wedge resection was performed. After immunohistochemical and genetic analysis, the lesion was characterized as a localized PEComa that was positive for Melan-A and Cathepsin-K on IHC, although negative for HMB-45. The current case contributes to the expanding histopathologic profile of these lesions.
Yolk sac tumor (YST) of the endometrium is very rare, with fewer than 40 cases reported in the English literature. We here describe a case of primary endometrial YST and discuss the clinicopathological features with a literature review. A 66-year-old Chinese woman presented with abnormal vaginal bleeding for 15 days and a uterine mass for 3 days. The preoperative alpha-fetoprotein (AFP) level was 9652.0 ng/mL, while other serum tumor markers, including carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and β-human chorionic gonadotropin (β-HCG), were 40.2 ng/mL, 29.19 ng/mL, and 27.7 mIU/mL, respectively. Pelvic ultrasound imaging revealed a 7.1 × 6.6 × 6.0 cm mass in the endometrial cavity. The patient underwent total abdominal hysterectomy, salpingo-oophorectomy, and partial omental resection. The morphologic and immunohistochemical pattern (cytokeratin+++, Sal-Like Protein 4+++, AFP++, Focal Hepatocyte Nuclear Factor 1 beta+, and Focal Glypican-3+) was consistent with a primary YST of the endometrium, and the final pathologic stage was IVb based on the International Federation of Gynecology and Obstetrics (FIGO) staging. Postoperative serum AFP level was 5193.0 ng/mL 5 days after the operation. Primary endometrial YST is extremely rare. It should be differentially diagnosed from other uterine malignancies. Complete surgical staging combined with chemotherapy may have a better survival impact on endometrial YST.
Background: Osteogenesis imperfecta (OI) is a group of skeletal dysplasias characterized by recurrent fractures and fragile bones. Two pathogenic variants in the IFITM5 gene cause distinct forms of OI: The recurrent c.-14C>T variant causes OI type V (MIM #610967), characterized by hyperplastic callus formation and interosseous membrane ossification, while the rare c.119C>T (p.Ser40Leu) variant causes a phenotypically distinct, severe form of IFITM5-related OI without these hallmark features. Radiographically, OI-related skeletal lesions may resemble malignant bone tumors such as osteosarcoma, leading to diagnostic challenges. Although the co-occurrence of OI and osteosarcoma has been reported, with approximately nine documented cases, all involved other OI subtypes. No case of true osteosarcoma arising in a patient with genetically confirmed IFITM5-related OI has been previously described. We present this case to highlight the novelty of this association, improve recognition of the distinguishing features, and prevent future misdiagnosis. Case Presentation: A 23-year-old female with IFITM5-related OI, confirmed by molecular testing showing heterozygosity for a pathogenic IFITM5 mutation (c.119C>T, p.Ser40Leu; parental testing to determine inheritance was not performed) presented to our Comprehensive Cancer Center in May 2025 with localized groin pain, later diagnosed as a nondisplaced pelvic fracture. Although initial clinical and radiographic findings were consistent with the patient ' s underlying OI, further evaluation revealed features concerning for concomitant osteosarcoma. The patient was treated with the MISER chemotherapy protocol with subsequent surgical resection. Conclusion: Distinguishing OI-related skeletal changes from malignant bone tumors requires integration of clinical history, genetic testing, and careful pathologic evaluation via a multidisciplinary approach. While prior reports of concomitant osteosarcoma and OI have involved other subtypes, this case represents the first documented true co-occurrence in a patient with IFITM5-related OI and underscores the importance of recognizing the overlapping and divergent features of these conditions when rendering a diagnosis and initiating treatment protocols.
Ovarian carcinosarcoma typically comprises high-grade carcinoma and sarcoma components. We report a case of a woman in her 40s with endometriosis-associated ovarian carcinosarcoma exhibiting an unusual presentation of well-differentiated adenocarcinoma and rhabdomyosarcoma. The patient underwent bilateral salpingo-oophorectomy and hysterectomy for tumors in both ovaries. Histologically, with a background of endometriosis, the epithelial component exhibited features of a borderline tumor with an intraepithelial carcinoma composed of Müllerian-type epithelium in both ovaries. In the left ovary, a very minor area of clear cell carcinoma (less than 5%) was identified. In contrast, the mesenchymal component was a well-differentiated rhabdomyosarcoma resembling fetal rhabdomyoma, constituting more than 60% of the left ovarian tumor. One year later, pulmonary metastases of the sarcomatous component were detected. Molecular analysis using next-generation sequencing identified PIK3CA H1047R (c.3140A>G) and CSF1R (c.∗1841TG>GA) in both the epithelial and mesenchymal components, indicating a clonal origin and supporting a diagnosis of primary ovarian carcinosarcoma. The patient died 29 months after surgery despite receiving platinum-based chemotherapy. This report highlights the challenges of diagnosing rare ovarian carcinosarcomas arising in endometriosis and with unusually low-grade histology, and it emphasizes the need for comprehensive pathological assessment, including molecular analysis, for accurate diagnosis and optimal management.
The co-occurrence of T-lymphoblastic leukemia/lymphoma and thymic neoplasia is a rare event that can present a diagnostic challenge. In this case report, we describe a 31-year-old man who was found to have thymic neuroendocrine carcinoma and T-lymphoblastic leukemia/lymphoma 2 years after initial treatment for T-lymphoblastic leukemia/lymphoma. The thymic neuroendocrine carcinoma was initially detected in a malignant pleural effusion, and a retrospective review of a preceding lung biopsy suggested the involvement of both tumors within one tissue sample. Immunohistochemical analysis was imperative in highlighting these two elements because despite their unique cytomorphological characteristics, a limited amount of each component was seen in the tissue biopsy. Ancillary testing is critical to the recognition of these entities in small biopsies.
: This case presents incidental heterotopic salivary gland tissue adjacent to a dermatofibrosarcoma protuberans (DFSP) located in the abdominal wall. The mature, functional heterotopic tissue was identified during Mohs micrographic surgery (MMS) performed for a DFSP, a slow-growing cutaneous tumor with locally aggressive and potentially malignant behavior. Definitive diagnosis of the heterotopic tissue was confirmed by histopathological examination and immunohistochemical analysis. This case underscores the importance of being alert to unusual tissue findings at the time of MMS and the value of close collaboration between dermatologists and pathologists.
Pulmonary adenoleiomyomatous hamartomas represent a rare and intriguing entity in pulmonary pathology. This study presents a unique case of adenoleiomyomatous hamartoma along with a comprehensive analysis of 14 cases identified through a systematic review of the literature. A 69-year-old Caucasian female presented for evaluation of an incidentally discovered, PET nonavid and slow-growing pleural-based nodule in the medial aspect of the lower lobe of her right lung. The biopsy showed pulmonary parenchyma with chronic inflammation, fibrosis, and smooth muscle hyperplasia. Subsequently, a diagnosis of pulmonary adenoleiomyomatous hamartoma was made on wedge resection after the exclusion of differential diagnoses. The literature review suggests a mean age of 54.5±3.5 years at diagnosis and male predominance with a male-to-female ratio of 6:1. Follow-up data on our patient and literature suggest a uniformly benign course. The key takeaways include the indolent radiologic growth pattern. From a pathologic standpoint, excluding mimics such as solitary fibrous tumor, inflammatory myofibroblastic tumor, PEComa, Langerhans cell histiocytosis, mesothelial proliferations, and IgG4-related diseases is crucial.
Urachal mucinous cystic tumour of low malignant potential (MCTLMP) is a rare cystic epithelial neoplasm of urachal origin, with fewer than 50 cases described as such in the English-language scientific literature. This case report describes an instance of urachal MCTLMP discovered incidentally in a 59-year-old female patient following the performance of imaging studies for an unrelated condition: Management consisted of surgical resection of the tumour and partial cystectomy, with no complications and no recurrence after 10 months of follow-up. Sections of the partial cystectomy specimen demonstrated histological features that were reminiscent of a low-grade appendiceal neoplasm or a borderline ovarian mucinous neoplasm, which were favoured to represent urachal MCTLMP. This case report highlights the clinical importance of both the complete surgical resection of tumour and the exclusion of secondary involvement of the bladder or urachus by a glandular tumour for the diagnosis of urachal MCTLMP and represents the emerging ‘typical’ clinical trajectory of a patient with urachal MCTLMP. Ongoing longitudinal study is required to better understand the longer term behaviour and clinical course of urachal MCTLMP.
BackgroundAdenoid cystic carcinoma (ACC) of the breast is an exceedingly rare malignancy, accounting for less than 0.1% of all breast cancers. It typically affects postmenopausal women and is exceptionally uncommon in men, with fewer than 20 cases reported in the literature. Histologically, ACC is a biphasic tumor composed of epithelial and myoepithelial cells with distinct cribriform, tubular, and solid-basaloid subtypes. Awareness of this condition in men is essential to prevent misdiagnosis and guide appropriate management.Case PresentationWe report the case of a 40-year-old man who presented with a painful right breast mass that had been present for 3 years. Ultrasonography revealed multiple solid lesions, and histopathological examination following surgical excision confirmed ACC with cribriform and solid patterns. Immunohistochemistry results were negative for ER, PR, HER2, and p53, with a Ki-67 index of 17%. Although a chest CT scan revealed suspicious bilateral pulmonary nodules, FDG-PET/CT did not reveal evidence of distant metastasis. Subsequent total mastectomy after 3 months revealed cribriform ACC without lymph node involvement. Due to imaging findings suggestive of possible local recurrence or residual disease, the patient was treated with adjuvant radiotherapy.ConclusionThis case highlights the importance of considering ACC in the differential diagnosis of breast masses in male patients. Given the rarity of this tumor in males, accurate histopathological and immunohistochemical diagnoses are critical to avoid misclassification. Although the overall prognosis is favorable, close follow-up is warranted because of the potential for recurrence and metastases.
Chronic histiocytic intervillositis (CHI) is a rare placental disorder characterized by an irregular and diffuse infiltration of the intervillous space by a monomorphic population of macrophages and monocytes. CHI is associated with adverse pregnancy outcomes, including intrauterine fetal demise, miscarriage, fetal growth restriction (FGR), and preterm birth. Its etiology remains unknown, and its pathophysiology is not fully understood; however, an underlying immune disorder targeting the semiallogeneic fetus has been proposed. Notably, CHI has undergone changes following the COVID-19 pandemic, now recognized as part of the SARS-CoV-2 placentitis triad.In this case series, we describe two pregnancies affected by CHI, highlighting their clinical relevance due to the immediate neonatal implications and the impact on maternal obstetric prognosis.
Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma defined by its characteristic multinodular myxoid architecture and distinctive clinicopathological features. Although EMC typically exhibits a multinodular myxoid architecture, its histologic variability and frequent immunophenotypic overlap with other myxoid tumors can make diagnosis challenging. We report a case of EMC arising around the left knee of a 73-year-old male patient. Histologically, the tumor exhibited abundant myxoid stroma with lace-like and haphazard cellular arrangements and focal epithelioid morphology. Immunohistochemically, the lesion showed diffuse positivity for several myoepithelial markers, including epithelial membrane antigen, α-smooth muscle actin, HHF35, calponin, and p63. However, the absence of cytokeratin and SOX10 expression raised diagnostic uncertainty despite the myoepithelial-like immunoprofile. Because immunohistochemistry remained inconclusive, targeted RNA sequencing was performed on formalin-fixed, paraffin-embedded tissue. A TAF15::NR4A3 fusion transcript was identified, leading to revision of the initial diagnosis to EMC. At 3-year follow-up, the patient remains free of recurrence or metastasis. This case demonstrates the potential for EMC to mimic myoepithelial tumors and supports the use of molecular analysis when histologic or immunohistochemical findings are insufficient for diagnosis.
BackgroundMorular metaplasia is a phenomenon described in neoplasms of various sites, including endometrioid neoplasms of the uterus and colonic tubular adenomas. Although of questionable biological significance, they may be confused with squamous differentiation/neoplasia or neuroendocrine lesions.Case PresentationA 34 year-old female patient on proton-pump inhibitor therapy underwent esophagogastroduodenoscopy for evaluation of bloating and reflux-type symptoms, which revealed three mucosal polyps within the proximal stomach. Microscopic examination showed conventional fundic gland polyps with foci of squamoid nests of whorled cells. These cells were positive for CDX2, demonstrated abnormal beta-catenin staining, and were negative for neuroendocrine markers. The diagnosis is fundic gland polyps with morular metaplasia.ConclusionThis case expands the types of lesions in which morular metaplasia may be identified, particularly in the setting of lesions with abnormalities of the Wnt/beta-catenin pathway protein expression, and raises awareness of the finding that may be confused with neoplastic lesions.
Introduction and Importance:Gallbladder carcinosarcoma (GBCS) is a rare and aggressive biliary tract malignancy, constituting approximately 1.7% of gallbladder cancers, with fewer than 100 cases reported in the English literature as of 2023. These tumors, often affecting gynecological organs, feature both carcinomatous and sarcomatous components. They predominantly occur in females, with a mean presentation age of 66 years. Diagnosis is primarily based on pathological analysis, and the mainstay of treatment is surgical excision. Presentation of Case:We present a case of an 81-year-old female with no significant medical history, who was admitted after a fall. A CT scan revealed an 18.2 cm gallbladder mass extending into the liver and colon. The patient underwent tumor resection. Pathological examination confirmed a carcinosarcoma with osteoid and cartilage elements, supported by immunohistochemical staining as gallbladder primary. Clinical Discussion:Carcinosarcomas are composed of both epithelial (commonly adenocarcinoma) and mesenchymal (spindle cell) components. Their pathogenesis remains poorly understood. Typically diagnosed at advanced stages, these tumors have a poor prognosis, with survival rates ranging from 2.9 to 6 months. Gallbladder carcinosarcomas behave similarly to sarcomas, exhibiting rapid growth and resistance to both radiation and chemotherapy. Current treatment consensus involves surgical excision of the gallbladder, extrahepatic bile duct, regional lymphadenectomy, and possibly pancreaticoduodenectomy depending on tumor extent. Conclusion:Gallbladder carcinosarcoma is a rare and aggressive malignancy with a poor prognosis even following complete resection. Given the limited number of cases, further research is necessary to improve treatment strategies for these patients.
Synchronous coexistence of plasma cell neoplasms (PCNs) and metastatic carcinoma is not a common phenomenon and poses a significant diagnostic challenge requiring meticulous histopathological and immunophenotypic analysis for accurate lineage assignment. We report two cases of collision tumors comprising PCN and metastatic lung carcinoma. Case 1 involved a 68-year-old male with metastatic non-small cell lung adenocarcinoma who developed intracranial lesions; resection revealed metastatic adenocarcinoma intermingled with clonal plasma cells. Case 2 was a 73-year-old woman with a lytic iliac crest lesion whose bone marrow and lesion biopsies showed diffuse infiltration by both carcinoma and atypical plasma cells. Comprehensive immunohistochemical profiling, in situ hybridization (ISH), and molecular studies were performed. In both cases, histology demonstrated two distinct, intermingled cell populations without transitional features. IHC was critical for confirmation: the carcinoma cells expressed epithelial markers (AE1/AE3), whereas the plasma cell components were positive for CD138. ISH in Case 1 and flow cytometry in Case 2 confirmed clonality (kappa light-chain restriction). The final diagnoses were collision tumors of metastatic non-small cell lung adenocarcinoma with synchronous PCN (Case 1) and metastatic small cell carcinoma with synchronous PCN (Case 2). There are sporadic reports of PCN coexistent in the same lesion with solid tumors. These cases reveal the critical role of the pathologist in diagnosing collision tumors. IHC panel, including cytokeratins, CD138, and MUM1, can help in distinguishing these dual populations and avoiding diagnostic pitfalls.
