Pulmonary Tumor Thrombotic Microangiopathy Caused by Metastatic Ovarian Cancer: An Antemortem Diagnosis with Pulmonary Aspiration Cytopathology.

A 48-year-old woman with advanced ovarian cancer was diagnosed with pulmonary tumor thrombotic microangiopathy (PTTM) by antemortem pulmonary wedge aspiration cytopathology. Despite the initiation of anti-cancer treatment, she unfortunately died due to progressive respiratory failure. Histopathology of the autopsied lung revealed multiple tumor embolization with fibrin-rich clot and fibro-cellular intimal proliferation at the pulmonary arteriole. The embolized tumor showed strong immune-positivity for pro-thrombotic and fibrotic factors (tissue factor and vascular endothelial growth factor), suggesting the underlying mechanisms of PTTM development. This case suggests that a quick antemortem diagnosis and the early induction of specific treatments might ensure a better prognosis of PTTM.

Diagnosis of Ion-Exchange Resin Depositions in Paraffin Sections Using Corrective Light and Electron Microscopy-NanoSuit Method.

Ion-exchange resins are commonly used to treat complications such as hyperkalemia, hyperphosphatemia, and hypercholesterolemia. Gastrointestinal complications may occur as side effects of such treatments. Sodium and calcium polystyrene sulfonate (PS-Ca) are cation-exchange resins comprising an insoluble structure that binds to potassium ions in the digestive tract and exchanges them with sodium and calcium ions, respectively, to promote their elimination. PS crystals are rhomboid, refractive, and basophilic in hematoxylin and eosin staining. To differentiate PS crystals from other ion-exchange resin crystals such as sevelamer and cholestyramine, periodic acid-Schiff, Ziehl-Neelsen, and Congo red staining are usually performed. Here, correlative light and electron microscopy (CLEM)-energy-dispersive X-ray spectroscopy and the NanoSuit method (CENM) was applied to perform a definitive identification of ion-exchange resins. CENM could detect sulfur in PS crystals without destroying the glass slides. Notably, PS retained its ion-exchange ability to bind potassium in paraffin sections. Differential diagnosis of anion-exchange resins, such as sevelamer and cholestyramine, was possible using these characteristics. The phosphorus:carbon ratio was higher in sevelamer than in cholestyramine after soaking paraffin sections in a phosphate solution. Therefore, CENM may be used for the differential pathological diagnosis of ion-exchange resins in paraffin sections.

Difference in the distribution of tumor-infiltrating CD8+ T cells and FOXP3+ T cells between micronodular thymoma with lymphoid stroma and micronodular thymic carcinoma with lymphoid stroma.

Micronodular thymoma with lymphoid stroma (MNT) is a rare thymic epithelial neoplasm subtype characterized by a micronodular tumor cell growth pattern and abundant lymphoid stroma. Micronodular thymic carcinoma with lymphoid stroma (MNCA) is considered as a malignant counterpart of MNT and exhibits a growth pattern similar to that of MNT but has histologic features reminiscent of thymic squamous cell carcinoma, such as cytologic atypia and CD5 and CD117 immunoexpression. Although both MNT and MNCA are characterized by abundant lymphoid stroma, it remains unknown whether there are differences in infiltrating lymphocytes between MNT and MNCA. We analyzed the immune microenvironment profile in eight MNT and three MNCA cases. The cell density of CD8-positive T cells was significantly higher in MNT than in MNCA, whereas that of FOXP3-positive T cells was significantly higher in MNCA than in MNT. There was no significant difference in the cell density of programmed death protein 1-positive T cells and programmed death ligand 1 expression between the MNT and MNCA cases. Our findings indicated that the immune microenvironment of MNCA differed from that of MNT and, compared with the T-cell profile of MNT, that of MNCA was more suppressive to patients' antitumor immune response.

Basaloid squamous cell carcinoma with adenoid cystic-like features of the head and neck region: A report of two cases.

The histology of basaloid squamous cell carcinoma (BSCC) can resemble that of adenoid cystic carcinoma (AdCC). Herein, we report two cases of BSCC with adenoid cystic-like features (BSCC-AdC). We collected cases of AdCC and BSCC of the head and neck region, extracted two cases with unusual histology, and reexamined them histologically and immunohistochemically. Case 1 involved an 81-year-old Japanese male, who had an elastic-hard mass on the left side of his tongue, and a biopsy examination suggested AdCC. Case 2 involved a 63-year-old Japanese male, who had a polypoid mass on his right hypopharynx. He was diagnosed with AdCC with high-grade transformation. Histologically, atypical cells in a myxoid stroma, which exhibited trabecular, nest-like, and/or cribriform growth patterns, and necrosis were observed in both cases. Case 2 displayed more marked cellular atypia than Case 1. Immunohistochemically, the tumor cells were diffusely positive for cytokeratin 5/6, p63/p40, SRY-related HMG-box 10 and Ki-67, but negative for other myoepithelial markers and p16. Finally, both cases were rediagnosed as BSCC-AdC. It is known that esophageal BSCC displays adenoid cystic-like features, and BSCC-AdC also sometimes occurs in the head and neck region. Clinicians should carefully differentiate BSCC-AdC from AdCC of the minor salivary glands and human papillomavirus-related carcinoma.

An Autopsy Case of a 5-Year-Old Child with Acute Pancreatitis Caused by Eosinophilic Granulomatosis with Polyangiitis-like Necrotizing Vasculitis.

In children, acute pancreatitis has been reported in IgA vasculitis, Kawasaki disease, systemic lupus erythematosus-associated vasculitis, and juvenile dermatomyositis-associated vasculitis. However, its frequency in these vasculitides has been shown to be low. In other childhood-onset vasculitides, acute pancreatitis is seldom reported. The patient was a 5-year-old Japanese boy who suddenly presented with gastrointestinal (GI) bleeding. Therapy with antiulcer drugs successfully stopped bleeding, but subsequently, high fever, leukocytosis, and hypoxia appeared. He died 12 days after he presented with GI bleeding. An autopsy unexpectedly revealed that necrotizing vasculitis with marked eosinophilic and histiocytic infiltration of the pancreas led to acute pancreatitis, and gastric ulcer with eosinophilic infiltration was shown to be the origin of GI bleeding. In addition, eosinophilic infiltration was found in the small intestine, lungs, and bone marrow. Necrotizing vasculitis with eosinophilic and histiocytic infiltration of the pancreas, eosinophilic infiltration of the airway wall, and eosinophilic gastroenteritis with gastric ulcer were histologically confirmed, suggesting that the present case may be an early stage of eosinophilic granulomatosis with polyangiitis- (EGPA-) like vasculitis. To our knowledge, this might be the first reported case of EGPA-like vasculitis presenting with acute pancreatitis in a child.

LTBP2 is secreted from lung myofibroblasts and is a potential biomarker for idiopathic pulmonary fibrosis.

Although differentiation of lung fibroblasts into α-smooth muscle actin (αSMA)-positive myofibroblasts is important in the progression of idiopathic pulmonary fibrosis (IPF), few biomarkers reflecting the fibrotic process have been discovered. We performed microarray analyses between FACS-sorted steady-state fibroblasts (lineage (CD45, TER-119, CD324, CD31, LYVE-1, and CD146)-negative and PDGFRα-positive cells) from untreated mouse lungs and myofibroblasts (lineage-negative, Sca-1-negative, and CD49e-positive cells) from bleomycin-treated mouse lungs. Amongst several genes up-regulated in the FACS-sorted myofibroblasts, we focussed on Ltbp2, the gene encoding latent transforming growth factor-ß (TGF-ß) binding protein-2 (LTBP2), because of the signal similarity to Acta2, which encodes αSMA, in the clustering analysis. The up-regulation was reproduced at the mRNA and protein levels in human lung myofibroblasts induced by TGF-ß1. LTBP2 staining in IPF lungs was broadly positive in the fibrotic interstitium, mainly as an extracellular matrix (ECM) protein; however, some of the αSMA-positive myofibroblasts were also stained. Serum LTBP2 concentrations, evaluated using ELISA, in IPF patients were significantly higher than those in healthy volunteers (mean: 21.4 compared with 12.4 ng/ml) and showed a negative correlation with % predicted forced vital capacity (r = -0.369). The Cox hazard model demonstrated that serum LTBP2 could predict the prognosis of IPF patients (hazard ratio for death by respiratory events: 1.040, 95% confidence interval: 1.026-1.054), which was validated using the bootstrap method with 1000-fold replication. LTBP2 is a potential prognostic blood biomarker that may reflect the level of differentiation of lung fibroblasts into myofibroblasts in IPF.