Background and Aim
The true incidence of incomplete muscularis mucosa resection with cold snare polypectomy (CSP) is unknown. We examined the incidence of incomplete muscularis mucosa resection both ...with and without cold snare defect protrusion (CSDP).
Methods
We prospectively enrolled patients undergoing polypectomy for 4 to 9mm nonpedunculated polyps. We evaluated the presence of CSDP immediately following CSP and biopsied the CSDP or the center of the mucosal defect without CSDP. The presence of the muscularis mucosa and any residual polyp in the biopsies was evaluated histologically. The primary outcome was the incidence of incomplete mucosal layer resection defined as the presence of muscularis mucosa or residual polyp in the biopsies.
Results
From August 2017 to October 2018, 188 patients were screened, and 357 polyps were included. CSDP was detected in 122/355 (34%) evaluated mucosal defects. Excluding five lesions requiring hemostasis immediately following CSP, 352 mucosal defects were biopsied. After excluding 102 biopsies containing normal mucosa, we evaluated 250 biopsies. The overall incidence of incomplete mucosal layer resection was 63% (159/250), 76% (68/90) with CSDP and 57% (91/159) without CSDP (P < 0.01). Both univariate and multivariate analyses showed that size (≥ 6 mm), resection time (≥ 5 s), and serrated lesions were risk factors for CSDP.
Conclusions
Cold snare defect protrusion (CSDP), which was present with 36%, was a good indicator for incomplete mucosal layer resection. Even in nonCSDP polypectomies, 57% of the mucosal layer was not removed completely. Thus, CSP should be used for intra‐epithelial lesions only, and careful pretreatment evaluation is recommended.
Secretory carcinoma (SC) of the salivary gland is a relatively newly described disease, separate from acinic cell carcinoma (ACC), which frequently displays ETV6-NTRK3 gene fusion. However, the ...differences between SC and ACC remain unclear. Here, histological reevaluation of 12 formerly diagnosed ACC cases was performed, which yielded a new diagnosis of SC in four cases due to a lack of obvious acinar-like cells. Immunohistochemically, phosphorylated signal transducer and activator of transcription 5 (p-STAT5) was expressed in SC but not in ACC, whereas discovered on GIST-1 (DOG1) was expressed in ACC but not in SC. Molecular analysis was possible in three SC cases, of which two showed the ETV6-NTRK3 fusion transcript on reverse-transcription polymerase chain reaction, as well as breaks in the ETV6 gene on fluorescence in situ hybridization. However, the remaining SC cases did not show this fusion transcript. Recently, several reports have suggested that SC might not be adequately diagnosed if the focus is placed solely on the ETV6-NTRK3 fusion gene due to genetic diversity. In this regard, immunohistochemistry of p-STAT5 and DOG1 is expected to be a useful alternative diagnostic tool to discriminate SC from ACC.
Lymphoepithelial carcinoma (LEC) shows characteristic histology of nesting growth of tumor cells with unclear differentiation against the lymphoid stroma background. Although rare in salivary glands, ...it has previously been recognized as a type of undifferentiated carcinoma but is currently clearly defined as an independent disease separate from undifferentiated carcinoma. We report a case of LEC that developed in the parotid gland and was immunohistochemically positive for p16, which suggested the causative involvement of human papillomavirus (HPV). The patient was a 38-year-old Japanese male aware of mass formation in the left parotid area for 8 years. Parotidectomy was performed and there have been no signs of recurrence or metastasis for 18 month post-operation. The tumor was histologically typical except for Epstein–Barr virus (EBV)-encoded small RNA (EBER)-negative in situ hybridization (ISH), but p16-positivity by immunohistochemistry, and also frequent contact with extended and expanded pre-existing ductal structures. Although usually strongly associated with EBV infection, the tumor could be regarded to have eventually reached completion as a LEC lesion associated with HPV infection possibly through the pathway shared with squamous cell carcinoma. EBER–ISH remains the most promising index for confirming diagnosis of LEC, but EBV-negative result alone should not prevent diagnosis of LEC.
Familial adenomatous polyposis (FAP) patients develop various life‐threatening extracolonic comorbidities that appear individually or within a family. This diversity can be explained by the ...localization of the adenomatous polyposis coli (APC) variant, but few reports provide definitive findings about genotype–phenotype correlations. Therefore, we investigated FAP patients and the association between the severe phenotypes and APC variants. Of 247 FAP patients, 126 patients from 85 families identified to have APC germline variant sites were extracted. These sites were divided into six groups (Regions A to F), and the frequency of severe comorbidities was compared among the patient phenotypes. Of the 126 patients, the proportions of patients with desmoid tumor stage ≥III, number of FGPs ≥1000, multiple gastric neoplasms, gastric neoplasm with high‐grade dysplasia, and Spigelman stage ≥III were 3%, 16%, 21%, 12%, and 41%, respectively, while the corresponding rates were 30%, 50%, 70%, 50%, and 80% in patients with Region E (codons 1398–1580) variants. These latter rates were significantly higher than those for patients with variants in other regions. Moreover, the proportion of patients with all three indicators (desmoid tumor stage ≥III, number of FGPs ≥1000, and Spigelman stage ≥III) was 20% for those with variants in Region E and 0% for those with variants in other regions. Variants in Region E indicate aggressive phenotypes, and more intensive management is required.
Familial adenomatous polyposis patients develop various life‐threatening comorbidities in the gastrointestinal tract and other organs. This study clearly elucidated a genotype–phenotype correlation in the APC gene developing severe extracolonic phenotypes.
Aims
Follicular lymphoma (FL), comprising a minor subset of primary thyroid lymphomas, is divided into two groups based on Bcl‐2 expression and IGH‐BCL2 translocation. The clinicopathological ...features exhibited by Bcl‐2‐negative IGH‐BCL2 translocation‐negative FL of the thyroid (Bcl‐2–/IGH‐BCL2– tFL) are different from those of conventional FL; however, its lymphomagenesis remains unclear. Here, we collected samples from seven patients with Bcl‐2–/IGH‐BCL2– tFL to investigate their epigenetic and genetic aberrations.
Methods and results
The immunohistochemical profiles of epigenetic modifiers and the methylation status of histones were examined, including EZH2, MLL2/KMT2D, CBP/CREBBP, EP300, H3K27me3 and H3K4me3, in Bcl‐2–/IGH‐BCL2– tFL and Bcl‐2‐positive IGH‐BCL2 translocation‐positive FL of the thyroid (Bcl‐2+/IGH‐BCL2+ tFL). Most Bcl‐2–/IGH‐BCL2– tFLs retained the positivity of epigenetic modifiers and lower expression of H3K27me3, although Bcl‐2+/IGH‐BCL2+ tFLs exhibited aberrant immunohistochemical patterns of EZH2 and CBP/CREBBP and overexpression of H3K27me3. Samples from seven cases were further analysed using targeted sequencing, focusing on the exons of 409 key tumour suppressor genes and oncogenes. Bcl‐2–/IGH‐BCL2– tFLs do not have pathogenic mutations of epigenetic modifiers, such as EZH2, MLL2/KMT2D, MLL3/KMT2C, EP300 and ARID1A, which have been reported in FLs in the literature, whereas Bcl‐2+/IGH‐BCL2+ tFLs are probably pathogenic/pathogenic missense mutations or frameshift mutations of these genes. Additionally, novel mutations in TET2 and EP400 were detected in Bcl‐2–/IGH‐BCL2– tFLs.
Conclusions
Different genetic and epigenetic abnormalities might be involved in the oncogenesis of Bcl‐2–/IGH‐BCL2– tFLs from Bcl‐2+/IGH‐BCL2+ tFLs and other FLs.
Carcinosarcoma is a clonal tumor developed through sarcomatoid changes in a carcinoma via the epithelial–mesenchymal transition (EMT). Here, we present an extremely rare case of pulmonary ...carcinosarcoma characterized by components suggesting pluripotency, namely neuroendocrine, myogenic, and chondrogenic differentiation, based on immunohistochemical analysis. A 42‐year‐old Japanese man was admitted to our hospital. Analysis of tumor tissue after right upper lobe lobectomy revealed a transition between carcinomatous and sarcomatous components. Immunohistochemical analysis suggested immortality owing to complete loss of p53 and diffuse expression of p16 in both the carcinomatous and sarcomatous components. There were also scattered cell groups expressing aldehyde dehydrogenase 1 family member A1, SOX2, CD133, and c‐kit, suggesting the possible presence of cancer stem cells. Our findings in this case suggested that the EMT may play a key role in mediating the immortality of tumor cells in carcinosarcoma and facilitating the pluripotency of cancer stem cells.
Adrenal incidentaloma is a clinically unapparent adrenal mass more than one cm in diameter detected during imaging performed not for adrenal disease. A 34-year-old man was evaluated for AI with a ...diameter of 3.5 cm in the left adrenal. He was obese with body mass index of 33,9. Blood pressure was 110–120/90 mmHg. The general laboratory tests were unremarkable. An adrenal hormone screening set revealed that ACTH was 6.9 pg/mL, cortisol 14.9 μg/dL, renin activity 0.9 ng/mL/h, aldosterone 79.4 pg/mL, dehydroepiandrosterone-sulfate (DHEA-S) measured on two occasions 5,217 ng/mL and 6,477 ng/mL (gender- and age-adjusted reference values, 1,060–4,640 ng/mL). The levels of metanephrine and normetanephrine were normal. The tumor was thought to produce solely DHEA-S. The excised left adrenal tissue contained a tumor with a diameter of 26 mm and neighboring adrenal tissue. The tumor consisted mostly of acidophil cells without necrosis, capsular or vascular invasion, and mitosis. Immunohistochemical study revealed followings: the cells of the tumors were stained positive for 3β-hydroxysteroid dehydrogenase, and 17α-hydroxylase, and 11β-hydroxylase, weakly positive for DHEA sulphotransferase, and negative for aldosterone synthetase. The atrophy of neighboring tissue was presumably caused by excess cortisol production. Four months after surgery, the cortisol level was 11.2 μg/dL and DHEA-S level 1,462 ng/mL. The tumor is considered to be a cortisol-producing adenoma with modestly excessive DHEA-S production rather than isolated DHEA-S-producing adenoma. Immunohistochemical study of steroidogenic enzymes is a valuable addition to blood hormone measurement to clarify steroid production profile.
Sclerosing mucoepidermoid carcinoma (SMC) is described as a “sclerosing variant” of mucoepidermoid carcinoma, and it is characterized by dense fibrosis and sclerosis of the stroma. SMC with ...eosinophilia (SMCE) is another and more rare subtype characterized by eosinophilia in addition to the sclerotic stroma common to SMC. However, unlike SMC, SMCE is not listed in the current 4th edition of WHO classification. Here, we describe three cases: one SMC in the parotid gland, one SMCE in the submandibular gland and one SMCE in the minor salivary gland of the oral cavity. The patients included a 71-year-old Japanese male, a 74-year-old Japanese female, and an 81-year-old Japanese female. They each complained of mass formation and underwent surgical resection. Histologically, the tumors mainly consisted of squamous cells with scarce keratinization that formed irregular large and small nests along with cystic structures containing mucous cells against the background of sclerotic stroma. One oral SMCE showed fine nesting and trabecular invasion. The two SMCEs included dense aggregates of eosinophils as well as more prominent lymphoid infiltration. Fluorescence in situ hybridization for
MAML2
confirmed split signals in SMC, but not in SMCE.
Secretory carcinoma of the salivary glands is a relatively new disease concept, and is characterized by “morphological resemblance to mammary secretory carcinoma and
ETV6–NTRK3
gene fusion.” Herein ...we describe a confusing case and briefly discuss practical diagnostic problems. The patient was a 71-year-old Japanese man who had a tumor consistent with secretory carcinoma at the microscopic and immunohistochemical levels. Immunohistochemically, EMA and S100 protein were noted to be positive along with various cytokeratins as well as mammaglobin and pSTAT5. Moreover, vimentin was focally positive. Smooth muscle actin, p63, p40, and androgen receptor were negative. However, a search using fluorescence in situ hybridization did not reveal a definite split signal for the ETV6 gene. It is presumed that confirming the diagnosis of secretory carcinoma without genetic retrieval will be accepted as a diagnostic method, and we hope that worldwide general recognition may earlier reach “gradual acceptance.”
