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To evaluate the feasibility of the glue-in-plug (GIP) technique using n -butyl-2-cyanoacrylate‒Lipiodol (NL)–iopamidol (NLI) for short-segment embolization in swine. The renal arteries, left external iliac artery, subclavian arteries, and common carotid arteries were each embolized in 4 swine using the GIP technique under general anesthesia. First, a type I Amplatzer vascular plug (AVP) (1–2 times the target vessel diameter) was deployed in the target artery. Next, the AVP was filled with NL mixture prepared at a ratio of 1:2 (NL12) (n = 11) or with NLI mixture prepared at a ratio of 2:3:1 (NLI231) (n = 11). Angiography was performed before, immediately after, and 1 hour after embolization to assess embolization and migration of the embolic materials. The embolized arteries were also evaluated histopathologically. The migration distance of the embolic material beyond the plug tip was significantly shorter in the NLI231 group than in the NL12 group immediately after embolization (6.5 mm ± 4.5 vs 1.0 mm ± 1.8, P =.0024) and 1 hour after embolization (8.4 mm ± 5.6 vs 1.0 mm ± 1.8, P =.0013). Angiography revealed no sign of recanalization of the target vessels in any artery in either group. Mild inflammatory cell infiltration was observed around the arterial wall at the embolization site in all arteries in both groups. The GIP technique using NLI231 may be a feasible procedure for short-segment embolization based on these short-term results. [Display omitted] [ABSTRACT FROM AUTHOR]

In 2020, acquired cystic disease-associated renal cell carcinomas (ACD-RCCs) were reported to harbor KMT2C and TSC2 variants: however, their carcinogenic implication has not yet been reported. This study aimed to explore the variant features of KMT2C and TSC2 in ACD-RCC and their implication in ACD-RCC tumorigenesis. Eleven ACD-RCCs, 10 ACD-RCC-like cysts, and 18 background kidneys were retrieved. The background kidneys consisted of atrophic thyroid follicle-like tubules. They included four with clustered cysts, two with eosinophilic changes, and one each with clear cell changes and sieve-like changes in the renal tubules. First, DNA-targeted sequencing of KMT2C and TSC2 whole exons was performed on eight ACD-RCC samples. Subsequently, a custom DNA panel was designed to include the recurrent KMT2C and TSC2 variants based on the sequencing results. Second, DNA-targeted sequencing was performed on the remaining samples using a custom panel targeting the recurrent variants. Additionally, immunohistochemistry was performed for KMTC, H3K4me1, H3K4me3, TSC2, and GPNMB on the ACD-RCCs. Six of the 11 ACD-RCC cases harbored KMT2C and TSC2 variants, including nine likely pathogenic variants. In contrast to ACD-RCC, 1 of the 9 ACD-RCC-like cysts harbored both variants. Immunohistochemical analysis did not support the loss of function in ACD-RCCs harboring KMT2C and TSC2 variants. KMT2C and TSC2 variant frequencies were higher in ACD-RCC than in other renal cell carcinomas. However, KMT2C and TSC2 are unlikely to be the primary drivers of ACD-RCC development. • Approximately half of ACD-RCCs harbored KMT2C and TSC2 variants. • Most ACD-RCC-like cysts and background kidneys did not harbor both variants. • KMT2C and TSC2 are unlikely to be the primary drivers of ACD-RCC development. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare complications and the number of ghrelin-expressing cells (GECs) after bariatric arterial embolization (BAE) using soluble gelatin sponge particles (SGSs) or tris-acryl gelatin microspheres (MSs) in swine. Twelve swine underwent embolization of gastric fundal arteries with SGSs (n = 4) or MSs (n = 4) or underwent saline infusion (n = 4, control group). One week later, the number of gastric ulcers and the percentage of GECs were compared among the 3 groups. There were no ulcers in the SGS and control groups. Two swine in the MS group had 4 large ulcers (12-50 mm in size). The mean percentages of GECs were significantly lower in the SGS (2.7% ± 0.9%) and MS (2.5% ± 1.0%) groups compared with the control group (3.7% ± 1.3%; P = .038 and P = .016, respectively). SGSs may be safer than MSs for BAE while inducing a similar reduction of GECs in swine. [ABSTRACT FROM AUTHOR]

• The cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is an uncommon variant of PTC, which incidence of CMV-PTC is less than 0.3% of PTC. • The strong expression of β-Catenin is a hallmark staining in CMV-PTC. • Total thyroidectomy in CMV-PTC with FAP should be performed at initial surgery due to high recurrence. The cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is an uncommon subtype of PTC, and it is associated with familial adenomatous polyposis (FAP). We describe a 32-year-old female who presented recurrent CMV-PTC with FAP. Surgery performed after the recurrent disease resulted in left recurrent laryngeal nerve palsy due to formation of strong scar after initial operation. The histopathological examination revealed the recurrent CMV-PTC without thyroid capsular invasion in remnant thyroid tissue of berry ligament. In addition, the immunohistochemical analysis showed that β-Catenin was diffusely positive in both cytoplasm and nucleus in CMV-PTC tissue. Total thyroidectomy in CMV-PTC with FAP should be performed at initial surgery due to high recurrence. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (CRCC) is well known for its intratumoral heterogeneity. Paneth-like cells (PLC) have been reported in variable organs (i.e., hepatobiliary, genitourinary, and female genital tract). In genitourinary system, it is possible to find PLCs in epididymis, urinary bladder and prostate. The objective of this study was to assess PLC in CRCCs 13 CRCCs with prominent PLC (CRCCPLC) were selected out of 1378 CRCCs in our registry. The tumors were analyzed using morphologic, immunohistochemical, ultrastructural, and molecular genetic methods. CRCCPLCs were mostly of low histologic grade (12/13). Immunohistochemical profile was compatible with classic CRCC. PLC constituted 10 to–70% of the tumor volume (mean 17.7%, median 10%). PLCs did not express neuroendocrine markers (chromogranin, synaptophysin, CD56, INSM-1). Ultrastructurally, PLCs were filled by membrane bounded vesicles of various sizes and were compatible with secretory type of cells. VHL mutation was found in 9/9 cases, and LOH3p was found in 6/8 analyzable cases. Conclusions: PLC morphology can variably be present in "classic" CRCC, even in a substantial proportion. Ultrastructurally, PLCs have all attributes of secretory cells. Preliminary follow up data showed that these tumors may not be associated with aggressive clinical behavior. • Paneth-like cells were reported in variable organs. • We assessed PLC in clear cell renal cell carcinomas. • 13 CRCCs with prominent PLC were selected. • Ultrastructurally, PLCs have attributes of secretory cells. • Follow up data indicated non-aggressive behavior. [ABSTRACT FROM AUTHOR]

Macroscopic cyst-formation by prostatic adenocarcinoma, herein referred to as macrocystic prostatic adenocarcinoma (MPA), is extremely rare. To date, no studies of prostate cancer performed based on gross cystic appearance have been reported. MPA can include various diseases, one of which is cystadenocarcinoma. Several cases of ductal adenocarcinoma exhibiting a macrocystic appearance have recently been reported; however, the histological and clinicopathological characteristics of MPAs have yet to be characterized and established. Therefore, we aimed to determine the histological and clinicopathological characteristics of MPA, via a multi-institutional investigation. We discovered five patients with MPA out of 1559 treated patients (0.32%); all cases were ductal adenocarcinomas. MPA was found to have three growth patterns: Two cases showed a prevalence of exuberant papillary proliferation with a fibrovascular core in the macroscopic multilocular cysts. Two others predominantly exhibited multilocular cysts lined by flat epithelium with foci of low papillae, and the fifth had a cystic lesion with intracancerous necrosis. Three of the cases showed extraprostatic invasion; however, none of the patients experienced recurrence during the follow-up period. Each predominant growth pattern tended to exhibit unique clinicopathological characteristics with respect to serum prostate specific antigen level and tumor size and location. In conclusion, we demonstrated that MPA is a ductal adenocarcinoma that is composed of intracystic exuberant papillary proliferation and flat proliferation with foci of low papillae, both of which might exhibit different clinicopathololgical appearances. [ABSTRACT FROM AUTHOR]

Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare cutaneous neoplasm with histopathologic similarities to nasopharyngeal carcinoma. The association of nasopharyngeal carcinoma with Epstein–Barr virus (EBV) is well documented. EBV has also been reported to be associated with LELC in only four sites (the stomach, salivary glands, lung, and thymus), but not in the skin. We report herein a case of EBV-positive LELCS. An 82-year-old female presented with a red nodule on the right cheek. Histologically, the entire dermis was occupied by atypical tumor cell nests with dense lymphocytic infiltration. Neoplastic cells were strongly positive for cytokeratin 14 but were negative for cytokeratins 19 and 20. EBV genomes in neoplastic cells were detected by polymerase chain reaction analysis and in situ hybridization for EBV-encoded RNA, suggesting an association with EBV. [Copyright &y& Elsevier]

Abstract: A case of exceptionally rare odontogenic malignant tumor, called ghost cell odontogenic carcinoma, is described. The tumor was considered to be derived from calcifying odontogenic cyst, which had been resected 5 years before. In the present resected specimen, cellular atypia, mitotic activity, Ki-67 labeling index, and p53 positivity were all increased in comparison with the initially resected specimen. This is a valuable case in which malignant transformation from calcifying odontogenic cyst to ghost cell odontogenic carcinoma was proven by the histopathologic and immunohistochemical findings. Pathologists should be aware of this rare entity. [Copyright &y& Elsevier]

Summary: BRAF (7q24) encodes a serine/threonine protein kinase, and its expression level varies in different tissues. Although a high prevalence of BRAF mutation has been suggested as an important event in thyroid tumorigenesis, little is known about the expression pattern of B-Raf in the thyroid. Thus, we examined the expression of B-Raf in various neoplastic and nonneoplastic thyroid tissues and compared it with BRAF mutational status. Normal and hyperplastic thyroid tissues showed focal and faint immunoreactivity for B-Raf, especially in cuboidal follicular cells of small follicles. In contrast, diffuse expression of B-Raf was observed in follicular adenomas and well-differentiated carcinomas. The missense point mutation BRAF V600E was identified in 42% (13/31 cases) of papillary carcinomas and 33% (5/15 cases) of undifferentiated carcinomas but not in normal thyroid tissues, nodular hyperplasia, follicular adenomas, or follicular carcinomas. The immunohistochemical expression of B-Raf did not correlate with BRAF mutational status. Moreover, Western blotting revealed that B-Raf expression in thyroid carcinoma cell lines was also independent of BRAF mutation. Serum or fibroblast growth factor-1 stimulation further activates ERK1/2 in heterozygous BRAF V600E-positive carcinoma cells as well as BRAF V600E mutation–negative carcinoma cells. In conclusion, heterogeneous focal expression of wild-type B-Raf in nonneoplastic tissues may play a role in the growth or functional activity of thyroid follicular cells. In contrast, diffuse expression of wild-type and/or mutant B-Raf may be involved in the tumorigenic process resulting in activation of the mitogen-activated protein kinase signaling pathway in cooperation with other genetic abnormalities and activation of ligand-receptor signaling pathways. [Copyright &y& Elsevier]

Summary: Aquaporin 3 (AQP3) acts as the membrane channel of water and other small solutes and plays a major role in fluid homeostasis. To investigate the expression of AQP3 in normal and neoplastic lung tissues, we studied a series of 149 lung carcinoma tissues and 2 cell lines by immunohistochemistry, Western blotting, and reverse transcriptase–polymerase chain reaction. In normal lung tissues, immunohistochemical expression of AQP3 was demonstrated in bronchial basal cells, alveolar type II cells, bronchiolar epithelial cells, and secretory cells of submucosal glands. In lung carcinomas, AQP3 expression was observed in 59 (70.2%) of 84 adenocarcinomas. Squamous cell carcinoma and large cell carcinoma had rather low positive ratios (35.8% and 13.4%, respectively). No AQP3 expression was demonstrated in small cell carcinoma, pleomorphic carcinoma, or metastatic colon adenocarcinoma. In adenocarcinomas, AQP3 was detected in all tumors of bronchioloalveolar subtype. Papillary subtype also showed a higher positive ratio of AQP3 compared with that in acinar and solid with mucin subtypes. In addition, AQP3 expression was related to tumor differentiation and clinical stage in adenocarcinomas. Western blotting and reverse transcriptase–polymerase chain reaction analyses confirmed the expression of AQP3 protein and messenger RNA in cell lines and tissues of lung adenocarcinoma. We conclude that AQP3 is widely expressed in the normal respiratory tract and can play an important role in the maintenance of water homeostasis. In addition, lung carcinomas, especially adenocarcinomas, can produce AQP3, possibly in connection with their functional and/or biological nature, although the detailed mechanism of AQP3 expression in lung carcinomas remains to be clarified. [Copyright &y& Elsevier]

Summary: We report on a case of mucinous carcinoma of the thyroid in an 82-year-old Japanese woman. The 3 × 2 × 2-cm thyroid tumor located in the patient''s right lateral lobe was soft and yellowish gray on the cut section. Microscopically, the tumor was composed entirely of strands or solid clusters accompanied by extensive extracellular mucin. Extracellular mucin was positive with Alcian blue stain and negative with periodic acid–Schiff stain. Immunohistochemically, the tumor cells were positive for thyroglobulin, thyroid-specific transcription factor 1, and low–molecular-weight cytokeratin but negative for carcinoembryonic antigen, calcitonin, and high–molecular-weight cytokeratin. The MIB-1 labeling index was rather high (11%), and immunoexpression of p53 was detectable in the nuclei of carcinoma cells. From these findings, we classified the present tumor as a mucinous carcinoma of the thyroid (poorly differentiated thyroid carcinoma producing massive extracellular mucin). The patient died of multiple metastases 4 years after the initial operation. [Copyright &y& Elsevier]

Summary: Stromal elastosis, defined as dense aggregations of elastic fibers, is found in some neoplastic tissues especially in malignant tumors of the breast and lung. Although also found in thyroid tissue, stromal elastosis in thyroid neoplasms have received little attention. To clarify the histopathological significance of stromal elastosis in the thyroid, we examined neoplastic (n = 223) and hyperplastic (n = 82) thyroid tissues in conjunction with cancer tissues (n =193) of various other organs. Stromal elastosis was observed as deposits of pale homogeneous material in hematoxylin and eosin stain, and distinctively highlighted by elastic-van Gieson''s stain. On immunohistochemical examination, elastin and tropoelastin were confirmed in these deposits. Stromal elastosis was found in 66% of papillary thyroid carcinomas (PTCs), although it was not identified in other histological types of thyroid neoplasms. In PTCs, deposits of elastic fibers varied in size and shape, and were more frequently distributed in the periphery of the tumor tissue. The histological subtypes of PTC varied in prevalence of elastosis with the follicular variant''s (9%) prevalence being significantly lower than that of the classical type (72%). The frequency of stromal elastosis in PTCs was very similar to the frequencies in breast and lung adenocarcinomas, and higher than the frequencies in carcinomas of other organs. In conclusion, our results suggest that stromal elastosis is a characteristic histological finding of PTCs, presumably associated with their growth pattern and/or histological architecture. It is, therefore, reasonable to propose that stromal elastosis is an ancillary feature in the histopathological diagnosis of PTCs. [Copyright &y& Elsevier]

Paneth-like cells (PLCs) are different from Paneth cells (PCs) and contain Paneth-like granules, which have been reported in non-neoplastic conditions and in neoplasms of various organs. PLCs have been reported in clear cell renal cell carcinoma (CCRCC), but not in non-CCRCC, including acquired cystic disease–associated renal cell carcinoma (ACD-RCC). We analyzed clinicopathological features of 24 acquired cystic disease–associated renal cell carcinoma (ACD-RCC) with PLCs (ACD-RCCP+) and compared with those of 23 ACD-RCCs without PLCs (ACD-RCCP−). Approximately half of ACD-RCCs had PLCs and that almost all kidneys harboring ACD-RCC had cysts with PLCs. The fact that many ACD-RCCs and the cysts had PLCs is further evidence that the cyst with vacuoles and complex architecture might be a precursor lesion for ACD-RCC. The presence of PLCs may provide additional morphologic clue for distinguishing ACD-RCC from PRCC in challenging differential diagnostic workup in acquired cystic disease of the kidney setting. • Paneth-like cells were found in ACD-associated RCC. • Same cells were found in non-neoplastic cysts in end-stage kidneys. • Presence of such cells supports hypothesis that such cysts might be precursor lesions. [ABSTRACT FROM AUTHOR]

A 72-year-old male had pseudomonal enteritis related to pembrolizumab. Chemotherapy for hypopharyngeal carcinoma with lung metastasis comprised cisplatin, 5-FU, and pembrolizumab. On day 14 of chemotherapy treatment he had a sudden prominent abdominal bulge, decreased consciousness, and drop in blood pressure in septic shock. CT scan showed marked intestinal gas through to intrahepatic bile ducts. Pseudomonas aeruginosa was simultaneously detected in both blood and stool cultures. Intestinal endoscopy revealed ulcerative lesions from the transverse colon to the rectum. Pathological investigations indicated apoptosis of the villus. The patient was diagnosed with pseudomonal enteritis induced by immune-related adverse events from the use of pembrolizumab. Treatment by corticosteroid and meropenem were subsequently switched to cefepime and metronidazole, and this successfully improved his colitis. In this new era of biological-targeted drugs and as clinical experience grows, we recommend a high level of alertness for potential diagnosis of infectious complications. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Cytology is well established and widely accepted method to diagnose lung tumors. However, cytological changes of malignant cells can be so subtle that cytopathologists cannot always diagnose with certainty. In such cases, some cytopathologists believe that radiological assessment is important for correct cytological diagnosis. However others deny the importance of radiological information, because they believe it could not change the cytological assessment. This study mainly aimed to clarify how radiologist''s comments affect cytological diagnosis of lung tumors. Methods: Of 201 patients who underwent cytological examinations, 131 and 57 patients were diagnosed with malignant and benign lung lesions, respectively. Study coordinators randomly selected 60 cytological slides each of the benign and malignant lesions. A radiologist graded their CT images by using a 5-point confidence scale. Three cytotechnologists assessed the 120 cytological slides twice on the basis of a 5-grade classification: first before and then after obtaining radiologist''s grading. Receiver operating characteristic analysis was performed. The Az values, sensitivities, and specificities of the cytological diagnoses were calculated for comparing the results before and after obtaining radiologist''s grading. Results: The mean Az value for cytological assessment after obtaining radiologist''s grading (0.88) was significantly higher than that before obtaining radiologist''s grading (0.78). The mean sensitivity of cytological assessment after obtaining radiologist''s grading (77%) was significantly higher than that before obtaining radiologist''s grading (67%). Conclusions: Radiological assessment, together with a radiologist''s confidence, improves cytological diagnoses of lung diseases. Thus, the importance to positively provide radiological assessment to cytopathologists should be considered by all clinicians. [Copyright &y& Elsevier]