Pathology International最新文献

Primary pulmonary hyalinizing clear cell carcinoma (HCCC) is a rare salivary gland-type tumor; most of the cases reported in the literature were diagnosed by surgical resection specimens. Herein, we present a case of pulmonary HCCC diagnosed with computed CT-guided percutaneous biopsy and discuss its clinicopathologic characteristics and diagnostic strategy. Microscopically, the lesion was mainly composed of small-to-medium-sized epithelioid cells with eosinophilic or transparent cytoplasm in a background of hyalinized fibrosis. The tumor cells showed immunoreactivity for CK and p63. The Ki67 proliferative index was 1%-5%, while TTF-1, CgA, S100, Syn, Desmin, SMA and PD-L1 staining were all negative. EWSR1 rearrangement was identified by break-apart fluorescence. The report highlights a case of pulmonary HCCC with negative PD-L1. The combination of tumor location, immunophenotypes and genetic alterations would be harnessed to differentiate HCCC from other tumors.

SMARCA4-deficient non-small cell lung cancer is characterized by highly aggressive clinical behavior, diverse tumor subtypes, and complex histological features. The application of the SMARCA4 immunohistochemical marker facilitates accurate identification. This study presents a rare case of SMARCA4-deficient pulmonary invasive mucinous adenocarcinoma with high-grade transformation.

Medullary thyroid carcinoma (MTC) with high proliferative potential or tumor necrosis is classified as high-grade MTC. Progression from low- to high-grade MTC has rarely been documented. We report a case in which a sporadic MTC transitioned from low- to high-grade after the initial therapy. A 62-year-old man with low-grade MTC underwent total thyroidectomy and bilateral neck dissection. Recurrence was identified postoperatively, and the surgical specimen of the lymph node revealed metastatic MTC with high-grade features. Treatment was initiated with vandetanib followed by selpercatinib, with no significant efficacy. Debulking surgery was performed for five recurrent lesions. Surgical specimens of the tumor after chemotherapy showed increased aggression, characterized by high Ki-67 index and decreased calcitonin expression. The patient eventually died due to brain metastasis. This case highlights the potential for MTC to progress from low- to high-grade and underscores the importance of ongoing evaluations for recurrent disease.

Solitary pulmonary capillary hemangioma (SPCH) is a rare, benign nodular lesion composed of proliferating capillaries in the lung. While pulmonary capillary hemangiomatosis-characterized by diffuse or patchy capillary proliferation in the lung leading to pulmonary hypertension and eventually fatal outcomes-has been recognized since 1978, the concept of solitary capillary hemangioma of the lung began to emerge in 2000 and has been increasingly recognized through subsequent reports. SPCH typically presents as a solitary nodule < 20 mm in diameter, often appearing as a ground-glass nodule on computed tomography. These features can closely mimic early-stage lung adenocarcinoma, posing a diagnostic challenge. In addition, SPCH is often difficult to palpate during surgery, which occasionally complicates intraoperative management. This review outlines the historical background of SPCH and summarizes its clinicoradiological, surgical (including intraoperative diagnosis), pathological (gross appearance and histopathological findings), and molecular characteristics. In particular, a literature review of previous studies, together with our own cases, highlights its distinguishing clinicoradiological features. Furthermore, SPCH is discussed in the broader context of pulmonary vascular tumors, and future directions for research and clinical practice are proposed.

Loeys-Dietz syndrome (LDS) is a rare autosomal dominant disorder whose clinical phenotype overlaps with that of Marfan syndrome (MFS) and vascular Ehlers-Danlos syndrome (vEDS), including aortic and/or arterial aneurysms, skeletal abnormalities, and spontaneous pneumothorax. Although the pathological features of MFS- and vEDS-associated pulmonary lesions have been described, the pulmonary pathology of LDS remains virtually unknown. Herein, we report the detailed histopathological features of LDS-associated pulmonary vascular abnormalities and pneumothorax. A 32-year-old Japanese woman underwent pulmonary surgery for spontaneous pneumothorax. She had undergone aortic valve surgery 7 years earlier, and genetic testing identified a heterozygous germline missense variant in TGFBR2 (c.1150 A > C, p.Asn384His). Histologically, the resected lung showed a ruptured bulla/bleb. Localized distal acinar emphysema was present in continuity with the bullous lesion. In the remaining parenchyma, the alveolar septa exhibited a distinctive proliferation of irregularly dilated and tortuous capillaries, reminiscent of pulmonary capillary hemangiomatosis. Hemosiderin-laden macrophages were conspicuous in some air spaces. In addition, several pulmonary muscular arteries and veins showed irregular dilatation and tortuosity, with elastic fibers that were fragmented and disorganized. Aberrant TGF-β signaling, together with deranged matrix formation, may underlie both the dilated, tortuous vasculature and the emphysematous/bullous changes leading to pneumothorax in the LDS lung.

We have established a highly stable and reproducible patient derived xenograft model that exclusively and robustly retains the morphological, functional, and proliferative characteristics of human yolk sac tumor of the testis. This model might provide an invaluable in vivo platform for accelerating the discovery and validation of novel therapeutic strategies for this aggressive malignancy, with the ultimate aim of improving the prognosis for affected patients.

Anaplastic pancreatic carcinoma (APC) arising from mucinous cystic neoplasm (MCN) is rare, with only 12 cases reported. The relationship between pregnancy-associaed hormonal changes and MCN progression remains poorly understood, particularly regarding hormone receptor expression patterns during malignant transformation. A 34-year-old woman presented with persistent abdominal pain 9 months post-delivery. Imaging revealed an 11 cm multilocular cystic mass in the pancreatic body and tail with mural nodules showing blood flow signals. Laboratory findings demonstrated normal. She underwent distal pancreatectomy and splenectomy and no recurrence at 6-month follow-up. Histopathological examination revealed MCN with ovarian-type stroma progressing from low-to-high grade dysplasia, invasive ductal carcinoma, and anaplastic carcinoma with osteoclast-like giant cells. Immunohistochemically, estrogen receptor (ER) expression showed stepwise pattern: negative in low-grade dysplasia, strongly positive in high-grade dysplasia and anaplastic components. Progesterone receptor positivity was observed in stromal and epithelial components, with elevated Ki-67 correlating with ER expression. This represents first documentation of progressive ER acquisition during MCN malignant transformation, suggesting autonomous hormone production by ovarian‑type stroma may help sustain tumor growth beyond pregnancy. Stepwise ER expression may serve as a biomarker for risk stratification and a potential target for therapy in hormone-sensitive pancreatic neoplasms.

The differential diagnosis of epithelioid mesothelioma and reactive mesothelial hyperplasia can be challenging based on morphology alone, particularly in small specimens. Consequently, the use of ancillary techniques, such as immunohistochemistry for BRCA1-associated protein 1, methylthioadenosine phosphorylase, and CDKN2A/p16 fluorescence in situ hybridization, has been considered a reliable method. Moreover, the potential of Merlin, enhancer of zeste homolog 2, 5-hydroxymethylcytosine, and c-Met immunohistochemistry in differential diagnosis has been reported. We conducted BRCA1-associated protein 1, methylthioadenosine phosphorylase, Merlin, enhancer of zeste homolog 2, 5-hydroxymethylcytosine, and c-Met immunohistochemistry in 43 epithelioid mesothelioma and 28 reactive mesothelial hyperplasia samples. BRCA1-associated protein 1 and/or methylthioadenosine phosphorylase achieved the highest sensitivity (83.7%), while the addition of Merlin improved the sensitivity to 86.0% while maintaining 100% specificity. We confirmed that the addition of Merlin to BRCA1-associated protein 1 and methylthioadenosine phosphorylase improved the sensitivity in the differential diagnosis of epithelioid mesothelioma and reactive mesothelial hyperplasia while maintaining 100% specificity. Moreover, the utilization of enhancer of zeste homolog 2, 5-hydroxymethylcytosine, and c-Met cannot be unequivocally endorsed, as these markers have not demonstrated 100% specificity, despite their capacity to modestly enhance sensitivity when employed in conjunction with BRCA1-associated protein 1 and methylthioadenosine phosphorylase.

Previously, we concluded that thyroid resections with multifocal, genetically distinct lesions more often showed florid chronic lymphocytic thyroiditis (CLT) than thyroids with clonally related multiple lesions. In this study, we characterized a consecutive cohort of thyroid lesions for molecular drivers and investigated the relationship between the molecular alteration type and florid CLT. Molecular diagnostic data from 414 patients (2016-2025) were retrospectively reviewed, including clinical information and histopathological evaluation. Gene fusion, somatic mutation, and chromosomal LOH/imbalance/copy-number analysis results were available for 342 cases. Eighty-eight gene rearrangements were identified across 86 patients. Most had been previously reported in thyroid neoplasia. Five well-known gene fusions revealed unusual breakpoints. Three gene fusions, previously reported only in nonthyroid malignancies (BRAF-TRIM24, SLC12A7-TERT, PVT1-MYC), were described for the first time in thyroid carcinoma. Three novel gene fusions (TRIM65-RET, FGFR2-WARS1, PPARGC1A-PPARɣ) produced in-frame translation products leading to corresponding mRNA expression. BRAF exon-skipping events were identified in treatment-naïve papillary thyroid carcinomas. Florid CLT (p = 0.002) and younger age (OR = 0.97 per year, p < 0.001) were independently associated with gene fusion-positive tumors. Sex, follicular nodular disease, and Graves' disease were not significant predictors. Our findings suggest an association between fusion-driven thyroid neoplasia and florid CLT, warranting further investigation.

Asthma is a recognized risk factor for nontuberculous mycobacterial (NTM) pulmonary infections, yet the precise routes of infection and dissemination remain visually unclear. We analyzed a rare surgical case of asthma complicated by Mycobacterium avium-associated lung cavity formation in a young adult. Following antibiotic treatment, the patient underwent left upper segmentectomy, with successful subsequent treatment of residual lesions using amikacin liposome inhalation suspension. To precisely visualize the infection route, we utilized a three-dimensional merged whole block imaging (WBI) technique. Fifteen formalin-fixed paraffin-embedded tissue blocks from the resected lung were individually scanned using a custom-built micro-computed tomography system, reconstructed, and combined to generate merged-WBI. Three core merged-WBIs revealed that the remodeled asthma-associated airway ascended from the proximal hilar region, intertwined with surrounding epithelioid granulomatous tissue, and then descended into a subpleural cavity composed of epithelioid granulomas with central caseous necrosis containing acid-fast bacilli. Besides the distinct airway path, the WBI delineated the distribution of minor epithelioid granulomas and calcifications. This report provides the first three-dimensional visualization of a continuous airway route extending from the hilum to a subpleural cavity using merged-WBI, suggesting bronchial spread as a probable mechanism of NTM dissemination in the setting of chronic airway disease. Clinical trial registration: No clinical trials.