[Clinicopathological features of verrucous type dysplasia of esophagus].

Objective: To investigate the clinicopathological features of verrucous type (squamous) dysplasia of esophagus. Methods: The clinicopathological data of 18 verrucous type dysplasia of esophagus patients in the 989th Hospital of the Joint Logistics Support Force of the People's Liberation Army (formerly 152 Central Hospital) and Beijing Chaoyang Hospital Affiliated to Capital Medical University from 2009 to 2021 were retrospectively collected. The histomorphologic characteristics and immunophenotype were observed, and human papillomavirus (HPV) genotyping was detected by PCR-fluorescence probe. The relevant literature was reviewed. Results: The median age of the 18 patients was 68 years (range 53-76 years); there were 13 males and 5 females. There were four cases in the upper esophagus, seven in the middle esophagus and seven in the lower esophagus. The median diameter of the lesion was 18 mm (range 6-54 mm). According to the Paris Classification, 11 cases were 0-Ⅱa, one case was 0-Ⅱa+Ⅰ, five cases were 0-Ⅱb, and one case was 0-Ⅱb+Ⅰ. White light endoscopy showed that the surface of the lesion was white plaque, red areas between the plaques, and papillary surface structure could be seen. In narrow-band imaging, some mucosal areas of lesions were opaque or patchy and light brown, and papillary microsurface structures were different in shapes and sizes. Intraepithelial microvessels were elongated, dilated, twisted and varied in diameter. Lugol iodine stain showed nil to faint staining. Histologically, the atypia cells were large with rounded to irregular nuclei, coarse chromatin, mitotic figures, and abundant eosinophilic cytoplasm. The basal cells showed increased atypia, crowding, increased nuclear-cytoplasmic ratio, and active mitosis. The cells were arranged haphazardly. Single cell keratinization, binuclear cells, and hollow-out-like cells, as well as surface epithelial keratinization and parakeratosis were observed in three cases. There were obvious verrucous or papillary structures in the epithelial layer. Five patients had local verrucous carcinoma. Immunohistochemical staining showed that the mutant expression of p53 protein in 6/10 cases; p16 was positive in 5/10 cases; abnormal Ki-67 distribution pattern in 10/10 cases. HPV was negative in all 10 cases tested. The original pathologic diagnosis of preoperative biopsy was high-grade dysplasia in 8 cases, low-grade dysplasia in 6 cases and atypical squamous epithelial cells in 4 cases. Conclusions: Esophageal verrucous dysplasia tumor cells are well differentiated with obvious verrucous or papillary structures. The unique morphological features suggest that it represents a histological subtype of esophageal squamous high-grade dysplasia and it is a precursor of verrucous carcinoma. Its preoperative biopsy diagnosis is challenging.

[Clinicopathological features of very well-differentiated adenocarcinoma of the stomach].

Objective: To investigate the clinicopathological features of very well-differentiated adenocarcinoma (VWDA) of the stomach. Methods: The clinicopathological data of 12 cases of VWDA of the stomach were collected retrospectively at the People's Liberation Army Joint Logistics Support Force 989 Hospital (formerly 152 Hospital), Pingdingshan, China, from January 2013 to May 2021. The histological characteristics and immunophenotypes were observed and analyzed with review of current literature. Results: There were 8 males and 4 females with a median age of 63 years (range 47 to 80 years). The tumor involved in the upper part of the stomach in 6 cases, the middle part in 2 cases, and the lower part in 4 cases. The median diameter of the tumors was 17 mm (range 5-65 mm). The tumor cells were similar to absorbent cells, Paneth cells, foveolar epithelial cells, and goblet cells. The cells were arranged in a single layer, and the nuclei were slightly enlarged and located at the base. The nuclei were fusiform to slightly irregular, with loss of nuclear polarity. Early tubular VWDA was found in 9 cases, and the tumor glands were similar to intestinal metaplasia. In two cases the tumors infiltrated into the submucosa. The lesions in the mucosa and submucosa showed the glands with cystic expansion, bending, branching, spiky and abortive growth pattern. One case of early papillary tubular VWDA was confined to the mucosal layer and composed of foveolar-type epithelial cells. There were two cases of advanced papillary tubular VWDA, which consisted of foveolar-type epithelial, pyloric glands, or mucinous neck cells and were associated with intra-lymphatic cancer embolus and lymph node metastases. Background mucosal atrophy and intestinal metaplasia were observed in all cases. Immunohistochemical staining showed intestinal type VWDA in 1 case, mixed gastrointestinal type VWDA in 9 cases, and gastric type VWDA in 2 cases. The Ki-67 proliferation index of 8 cases limited to the mucosa was 40%-70%, 2 cases of infiltration into the submucosa and 2 cases of advanced carcinoma was 10%-25%. All the tumors showed a wild type of p53 protein expression pattern and negative HER2. Adenocarcinoma or high-grade dysplasia was diagnosed on preoperative biopsy in 5 cases, and chronic atrophic gastritis with intestinal metaplasia in 7 cases. The median follow-up time was 28 months (range 12-72 months). No recurrence was found in the 10 patients with early cancer. Of the two patients with advanced carcinoma, one patient had lung metastases and the other died. Conclusions: Gastric VWDA is a rare low-grade malignancy with structural features of highly differentiated adenocarcinoma and extremely low cytological atypia. The diagnostic value of structural abnormality is significantly greater than cytological atypia. The invasive growth of irregular glands in the deep mucosa and submucosa is reliable evidence for diagnosis. The diagnosis of intramucosal VWDA is challenging and very difficult in some biopsy specimens.

[Clinicopathological features of differentiated-type dysplasia of the esophagus].

Objective: To investigate the clinicopathological features of differentiated-type (squamous) dysplasia of the esophagus. Methods: A total of 184 cases of esophageal differentiated-type dysplasia were collected retrospectively at People's Liberation Army Joint Logistics Support Force 989 Hospital (formerly 152 Hospital), and Beijing Chaoyang Hospital, Capital Medical University, China from 2016 to 2019. Their histological characteristics and immunophenotypes were analyzed, and related literature was reviewed. Results: The median age of the 184 patients was 65 years (range 39-83 years), while the ratio of men to women was 1.7∶1.0. There were 17 cases in the upper esophagus, 143 in the middle esophagus and 24 in the lower esophagus. The median diameter of the dysplasia was 15 mm (range 2-50 mm). According to the Paris classification, 2 cases were 0-Ⅰ, 25 cases were 0-Ⅱa, 70 cases were 0-Ⅱb, 74 cases were 0-Ⅱb and 0-Ⅱc and 13 cases were 0-Ⅱc. Macroscopically, the lesional mucosa was reddish with rough surface and white moss; capillary abnormality was found on narrow-band imaging. Histologically, dysplastic cells had distinct features of squamous epithelium, with abundant eosinophilic cytoplasm, round to irregular nuclei, coarse chromatin, obvious nucleolus, and conspicuous mitoses. The cellularity was increased, the arrangement of cells was disordered, and the polarity of cells in basal layer was lost. When the dysplasia did not completely spread to the whole layer of squamous epithelium, a clear boundary was often formed between the dysplasia and the normal epithelium above it. The neoplastic epithelial protrusions often grew toward the lamina propria and were accompanied by conspicuous inflammatory cell reaction at its frontal edge. Sometimes, abnormal mature single epithelial cells or cell clusters infiltrated into the lamina propria. There were high-grade dysplasia of the common type and superficial invasive squamous cell carcinoma in 98 cases of differentiated-type dysplasia. Immunohistochemical staining showed that the mutation rate of TP53 was 47.7% (53/111). The median of Ki-67 labeling index was 50.0% (range 10%-80%), while that of basal tumor cells was 12/HPF (range 3-65/HPF). The abnormal distribution pattern of Ki-67 was seen in 111 (100%) cases. According to the initial pathological diagnosis, there were 16 cases of low-grade intraepithelial neoplasia, 37 cases of atypical epithelial cells and 131 cases of high-grade intraepithelial neoplasia and superficial invasive squamous cell carcinoma. Conclusions: The morphology of differentiated-type dysplasia of the esophagus is unique. Characteristics of highly differentiated dysplastic cells suggest that they may represent a differentiated type in the morphological lineage of esophageal squamous (high-grade) dysplasia. When the knowledge of the lesion is insufficient, it is easy to be misdiagnosed or missed in pathologic examination.

[Spindle cell type squamous dysplasia of the esophagus: a clinicopathological analysis].

Objective: To investigate the clinicopathological features and significance of spindle cell type squamous dysplasia of the esophagus. Methods: The clinicopathological data of 37 cases of spindle cell type squamous dysplasia of esophagus were collected retrospectively at People's Liberation Army Joint Logistics Support Force 989 Hospital (formerly 152 Hospital), Pingdingshan, China, from 2009 to 2019. The histological and immunohistochemical characteristics were analyzed, with a literature review. Results: The median age of the 37 patients was 65 years (range 47-81 years), while the ratio of men to women was 1.5∶1.0. There were 4 cases in the upper esophagus, 31 in the middle esophagus and 2 in the lower esophagus. The median diameter of the lesions was 14 mm (range 3-40 mm). According to the Paris classification, 11 cases were 0-Ⅱa, 14 cases were 0-Ⅱb, 3 cases were 0-Ⅱb and 0-Ⅱa, and 9 cases were 0-Ⅱc. Under endoscope, the lesional mucosa was reddish. The micro-vessels were dilated, with various shapes and density. Histologically, tumor cells and nuclei were spindle shaped or elongated spindle shaped, with considerable homogeneity, dark nuclei and delicate or slightly thickened chromatin. The mitosis was conspicuous, and atypic mitoses were seen; the cytoplasm was acidophilic, and the intercellular bridge was obvious. The cells were dense and often lost polarity, but still arranged in parallel, mostly perpendicular to the basement membrane. Spindle cells often involved the whole layer of epithelium, with no gradient maturation and differentiation of normal squamous epithelium. The tumor was well demarcated. The spindle cells often invaded lamina propria. There were 15 cases with focal high-grade dysplasia and superficial invasive squamous cell carcinoma. Immunohistochemical staining showed that the mutation rate of p53 was 41.4% (12/29), the median of Ki-67 labeling index was 40% (range 20%-80%), and the abnormal distribution pattern of Ki-67 was 29 (100%). According to the initial pathological diagnosis, there were 6 cases of low-grade dysplasia, 4 cases of atypical epithelial cells and 27 cases of high-grade dysplasia and superficial invasive squamous cell carcinoma. Conclusions: Spindle tumor cells have moderate to severe atypia, and some tumors show invasive pattern. P53 mutation and Ki-67 abnormal distribution pattern indicate that they are high-grade dysplasia of esophageal squamous epithelium. The unique characteristics of spindle tumor cells suggest that they may represent a spindle cell subtype in the morphological spectrum of esophageal squamous dysplasia. When the knowledge of the lesion is insufficient, it can be easily misdiagnosed or missed.

[Role of Claudin-1 on diagnostic cut-off value and multiple tests in patients with papillary thyroid carcinoma].

Objective: To explore the diagnostic cut-off value of Claudin-1 (Cla-1) in papillary thyroid carcinoma (PTC) and the efficacy of the multiple test. Methods: Clinical and pathological data were collected from 295 patients with PTC and 137 patients with benign thyroid lesions (BTL) admitted to two hospitals in Pingdingshan City, Henan Province from January 2015 to June 2020. The expression index of Cla-1, the positive expression rate of high molecular weight cytokeratin (HMW-CK) and the negative expression rate of leukocyte differentiation antigen 56 (CD56) were calculated according to the results of immunohistochemistry. Receiver operating characteristic (ROC) curve was used to determine the cut-off value of Cla-1 for diagnosing PTC. Cla-1+HMW-CK, Cla-1+CD56, HMW-CK+CD56 and Cla-1+HMW-CK+CD56 were tested in series, and the diagnostic efficacy was evaluated by sensitivity, specificity and accuracy. Results: The age of PTC patients M (P25, P75) was 48.0 (41.0, 55.0) years old, among which 230 cases were male (78.0%). The age of BTL patients M (P25, P75) was 53.0 (46.0, 61.0) years old, including 34 males (24.8%). Cla-1 detection was conducted in all PTC and BTL patients, whereas only 198 and 97 cases conducted HMW-CK detection, 242 and 136 cases conducted CD56 detection, respectively. The M (P25, P75) of Cla-1 expression index in PTC was 80.0% (45.0%, 90.0%), which was higher than that in BTL [0.0 (0.0, 2.0%)] (P<0.001). The positive expression rate of HMW-CK was 93.9% (186/198) in PTC, and was negative in all BTL. The negative expression rate of D56 was 89.7% (217/242) in PTC, higher than that of BTL [1.5% (2/136)] (P<0.001). When expression index 19.0% was set as the cut-off value of Cla-1 for diagnosing PTC, the area under the ROC curve (AUC) was the maximum [AUC (95%CI): 0.981 (0.969, 0.994)], and the sensitivity, specificity and accuracy were 92.2% (272/295), 98.5% (135/137) and 94.2% (407/432), respectively. In multiple tests for diagnosis of PTC, the sensitivity ranged from 89.3% to 94.7%, specificity were all 100.0% and accuracy ranged from 93.1% to 96.9%. Conclusion: Cla-1 expression index ≥19.0% could be set as a cut-off value for the diagnosis of PTC and serial test of Cla-1 combined with HMW-CK(CD56) improves diagnostic specificity.

[Clinicopathological features of basal cell type dysplasia of esophagus].

Objective: To investigate the clinicpathological features of basal cell type dysplasia of the esophagus. Methods: The clinicopathological data of 71 cases of basal cell type dysplasia of esophagus were collected at the People's Liberation Army Joint Logistics Support Force 989 Hospital, from 2009 to 2019, and the histomorphologic characteristics and immunophenotype were evaluated. The relevant literature was reviewed. Results: The ratio of male to female patients was 1.6∶1.0, and the median age was 65 years (range 48-81 years). The tumors were located in the upper segment of the esophagus in four cases (5.6%), the middle segment in 54 cases (76.1%), and the lower segment in 13 cases (18.3%).The median maximal tumor diameter was 12.0 mm (range 3-42 mm). According to Paris Classification, 0-Ⅱb accounted for 42.3% (30/71) of the cases. Under endoscope, the lesions were reddish with abnormal mucosal microvessels. Histologically, the neoplastic cells were small, with a high nuclear-cytoplasmic ratio, similar to basal cells, and uniform in morphology. The structural atypia was characterized by dense and disordered tumor cells, loss of basal cell polarity, and absence of normal squamous differentiation gradient. In 10 cases, the tumors were confined to the lower part of the epithelium. The tumor cells were smaller and more uniform in shape, and extend to the superficial lamina propria. Sixty-one tumors involved at least the entire layer of the upper cortex. There were 31 cases of neoplasms with superficial invasive carcinoma. The types of neoplasms included typical squamous cell carcinoma, basaloid squamous cell carcinoma, small cell neuroendocrine carcinoma, squamous cell carcinoma with sebaceous adenoid carcinoma, and differentiation of glandular/ductal epithelioid carcinoma. Immunohistochemical staining showed that the mutant expression rate of p53 protein was 41.5% (17/41). All 41 cases (100.0%) showed abnormal distribution pattern of Ki-67. According to the initial pathologic diagnosis, there were 18 cases of low grade dysplasia, 12 cases of atypical epithelial cells, and 41 cases of high grade dysplasia and superficially invasive carcinoma. Conclusions: Basal cell type dysplasia has unique morphologic characteristics and represents a tumor subtype in the morphologic lineage of esophageal squamous dysplasia. Tumor cells of basal cell type dysplasia, especially those distributed only in the lower part of the stratified squamous epithelium, may be tumor stem cells at the earliest stage of esophageal carcinogenesis and have multidirectional differentiation potential. When the tumor is confined to the lower part of the stratified squamous epithelium, it does not meet the diagnostic criteria for esophageal squamous dysplasia as defined by the current WHO classification.

[Clinicopathological features of basal cell layer type high-grade squamous dysplasia of the esophagus].

Objective: To investigate the clinicopathological features of basal cell layer type high-grade squamous dysplasia of the esophagus. Methods: Fifty-two cases of basal cell layer type high-grade squamous dysplasia of the esophagus were collected at PLA Joint Logistics Support Force 989 Hospital (34 cases) and Beijing Chaoyang Hospital (18 cases) from 2009 to 2019. The clinical, histological and immunohistochemical features were characterized. Related literature was also reviewed. Results: The median age of the 52 patients was 64 years (range 43-72 years). There were 35 men and 17 women, with a male to female ratio of 2.1∶1.0. There were 8 cases in the upper esophagus, 41 in the middle esophagus and 3 in the lower esophagus. According to the Paris Classification, 24 cases were 0-Ⅱb and 28 cases were 0-Ⅱc. Endoscopic examination showed that the color of the lesions was red and the edge was irregular. The narrow band imaging showed that the lesions were brown, and the microvascular abnormalities on the mucosal surface were observed with high magnification. Iodine staining of the lesions showed no or light staining and irregular border. Histologically, the basal layer of squamous epithelium was hypercellular, with large and hyperchromatic nuclei, and disordered cell arrangement. A high proportion of the cases showed a down-growth pattern and associated invasive squamous cell carcinoma. The immunohistochemical staining of 37 cases showed that the mutation rate of p53 was 48.6% (18/37), the median of Ki-67 labeling index was 60% (range 20%-90%), the median of Ki-67 labeling index of the basal tumor cells was 26/HPF (range 5-70/HPF), and the rate of abnormal Ki-67 distribution pattern was 37(100.0%). According to the initial pathological diagnosis, there were 8 cases of low-grade intraepithelial neoplasia, 2 cases of atypical epithelial cells and 42 cases of high-grade intraepithelial neoplasia. Conclusions: The basal cell layer type high-grade squamous dysplasia of the esophagus has a unique morphology. The dysplasia is mainly limited to the lower half part of the squamous epithelium. With marked cytological atypia and prominent invasiveness pattern, it is likely to develop into invasive squamous cell carcinoma at an early stage of the disease. The rate of pathologic misdiagnosis (such as low-grade lesion) is high. The p53 mutation and Ki-67 abnormal distribution pattern are helpful features for confirming the diagnosis of such high-grade dysplasia.

[Pathological characteristics of colorectal adenoma with submucosal pseudoinvasion].

Objective: To investigate the pathomorphological characteristics of colorectal adenoma with submucosal pseudoinvasion and to summarize the corresponding pseudoinvasion patterns. Methods: The clinicopathological data of 9 cases of colorectal adenoma were collected at 989 Hospital of PLA Joint Logistics Support Force (4 cases) and Beijing Chaoyang Hospital, Capital Medical University (5 cases), from 2016 to 2019. retrospectively, and the histomorphological characteristics and immunophenotypes were analyzed, and discussed in light of the relevant literature. Results: There were 8 cases of adenoma with stalk. Tumor glands were found in the submucosa at the head end of adenoma, similar to infiltrating adenocarcinoma. The structure and cellular morphology of submucosal glands were very similar to the intramucosal tumor while the local submucosal tumor showed continuity with the intramucosal tumor. The submucosal tumors were lobule-like or nest-like with clear boundary. The outline of the gland was smooth and blunt-round, and there was loose fibromyxoid stroma around the gland, similar to the mucosa propria stroma. Some cases of the submucosal glands were cystic dilated with mucocele formation and hemosiderin deposition. One case with broad stalk-base showed an elevated adenoma with local high grade dysplasia involved in the aggregated lymphoid nodule, forming the lymphoglandular complexes, simulating invasive adenocarcinoma with associated submucosal lymphoid aggregates. Submucosal cancer tissue and intramucosal cancer tissue had continuity, and their morphology was the same. The submucosal tumor was round in the outline, smooth and blunt in the edge, and surrounded by lymphoid tissue. There was no stromal response around the gland to promote the proliferation of connective tissue, neither was there single-cell or small-cell cluster, sharp angle branch of gland, or vascular infiltration. Conclusions: There are two unique morphological patterns in colorectal adenoma with submucosal pseudoinvasion. Morphologically, the data show that one is lobular-like pattern, and the other is lymphoglandular complexes-like pattern. The main features of the two patterns are the same-morphology and continuity of submucosal tumor and intramucosal tumor. The pushed glands were surrounded by the intrinsic membrane stroma and muscularis mucosae in proper order, lacking the typical morphological characteristics of invasive adenocarcinoma.