Specific Expression of Human Intelectin-1 in Malignant Pleural Mesothelioma and Gastrointestinal Goblet Cells

Malignant pleural mesothelioma (MPM) is a fatal tumor. It is often hard to discriminate MPM from metastatic tumors of other types because currently, there are no reliable immunopathological markers for MPM. MPM is differentially diagnosed by some immunohistochemical tests on pathology specimens. In the present study, we investigated the expression of intelectin-1, a new mesothelioma marker, in normal tissues in the whole body and in many cancers, including MPM, by immunohistochemical analysis. We found that in normal tissues, human intelectin-1 was mainly secreted from gastrointestinal goblet cells along with mucus into the intestinal lumen, and it was also expressed, to a lesser extent, in mesothelial cells and urinary epithelial cells. Eighty-eight percent of epithelioid-type MPMs expressed intelectin-1, whereas sarcomatoid-type MPMs, biphasic MPMs, and poorly differentiated MPMs were rarely positive for intelectin-1. Intelectin-1 was not expressed in other cancers, except in mucus-producing adenocarcinoma. These results suggest that intelectin-1 is a better marker for epithelioid-type MPM than other mesothelioma markers because of its specificity and the simplicity of pathological assessment. Pleural intelectin-1 could be a useful diagnostic marker for MPM with applications in histopathological identification of MPM

Stromal micropapillary pattern predominant lung adenocarcinoma - a report of two cases

Generally, adenocarcinomas with micropapillary pattern, featuring small papillary tufts lacking a central fibrovascular core, are thought to have poor prognosis. This pattern has been described in various organs. However, tumor cells with micropapillary pattern of lung adenocarcinoma are more often seen to float within alveolar spaces (aerogenous micropapillary pattern, AMP) than in fibrotic stroma like other organs (stromal micropapillary pattern, SMP) and SMP predominant lung adenocarcinoma (SMPPLA) has not been well described yet. We presented two cases of SMPPLA which were found in the last four years. Both the cases showed more than 50% of SMP in the tumor area. The majority of the stromal micropapillary clusters expressed MUC1 and epithelial membrane antigen along the outer surface of cell membrane. On the other hand, connective tissues surrounding stromal micropapillary clusters showed no reactivity for epithelial markers (thyroid transcription factor-1 and cytokeratin) or endothelial marker (D2-40 and CD34). It means clusters of SMP do not exist within air space or lymphatic or vessel lumens. The tumors with SMP often presented lymphatic permeation and vessel invasion, and intriguingly, one of the two cases showed metastasis to the mediastinal lymph node. Additionally, both the cases showed EGFR point mutations of exon 21. These results suggest that SMPPLA might be associated with poor prognosis and effective for EGFR tyrosine kinase inhibitors

Single cell RNA-seq reveals profound transcriptional similarity between Barrett's oesophagus and oesophageal submucosal glands

Barrett’s oesophagus is a precursor of oesophageal adenocarcinoma. In this common condition, squamous epithelium in the oesophagus is replaced by columnar epithelium in response to acid reflux. Barrett’s oesophagus is highly heterogeneous and its relationships to normal tissues are unclear. Here we investigate the cellular complexity of Barrett’s oesophagus and the upper gastrointestinal tract using RNA-sequencing of single cells from multiple biopsies from six patients with Barrett’s oesophagus and two patients without oesophageal pathology. We find that cell populations in Barrett’s oesophagus, marked by LEFTY1 and OLFM4, exhibit a profound transcriptional overlap with oesophageal submucosal gland cells, but not with gastric or duodenal cells. Additionally, SPINK4 and ITLN1 mark cells that precede morphologically identifiable goblet cells in colon and Barrett’s oesophagus, potentially aiding the identification of metaplasia. Our findings reveal striking transcriptional relationships between normal tissue populations and cells in a premalignant condition, with implications for clinical practice

Differential diagnosis of uterine adenosarcoma: identification of JAZF1-BCORL1 rearrangement by comprehensive cancer genomic profiling

Abstract Background Uterine adenosarcoma is a rare malignant tumor that accounts for 8% of all uterine sarcomas, and less than 0.2% of all uterine malignancies. However, it is frequently misdiagnosed in clinical examinations, including pathological diagnosis, and imaging studies owing to its rare and non-specific nature, which is further compounded by the lack of specific diagnostic markers. Case presentation We report a case of uterine adenosarcoma for which a comprehensive genomic profiling (CGP) test provided a chance to reach the proper diagnosis. The patient, a woman in her 60s with a history of uterine leiomyoma was diagnosed with an intra-abdominal mass post presentation with abdominal distention and loss of appetite. She was suspected to have gastrointestinal stromal tumor (GIST); the laparotomically excised mass was found to comprise uniform spindle-shaped cells that grew in bundles with a herringbone architecture, and occasional myxomatous stroma. Immunostaining revealed no specific findings, and the tumor was diagnosed as a spindle cell tumor/suspicious adult fibrosarcoma. The tumor relapsed during postoperative follow-up, and showed size reduction with chemotherapy, prior to regrowth. CGP was performed to identify a possible treatment, which resulted in detection of a JAZF1-BCORL1 rearrangement. Since the rearrangement has been reported in uterine sarcomas, we reevaluated specimens of the preceding uterine leiomyoma, which revealed the presence of adenosarcoma components in the corpus uteri. Furthermore, both the uterine adenosarcoma and intra-abdominal mass were partially positive for CD10 and BCOR staining. Conclusion These results led to the conclusive identification of the abdominal tumor as a metastasis of the uterine adenosarcoma. The JAZF1-BCORL1 rearrangement is predominantly associated with uterine stromal sarcomas; thus far, ours is the second report of the same in an adenosarcoma. Adenosarcomas are rare and difficult to diagnose, especially in atypical cases with scarce glandular epithelial components. Identification of rearrangements involving BCOR or BCORL1, will encourage BCOR staining analysis, thereby potentially resulting in better diagnostic outcomes. Given that platinum-based chemotherapy was proposed as the treatment choice for this patient post diagnosis with adenosarcoma, CGP also indirectly contributed to the designing of the best-suited treatment protocol

Insignificant expression of intelectin-1 in non-MPM cancers that lack mucus production.

<p>Specimens were immunostained with MPM markers, and representative photographs are shown. A scale bar (100 µm) is shown in the bottom side of panel A, representatively. <b>A</b>, intelectin-1 staining of a colon adenocarcinoma (AD) lacking mucus production; <b>B</b>, intelectin-1 staining of mucus-producing colon AD; <b>C</b>, intelectin-1 staining of a gastric AD lacking mucus production; <b>D</b>, intelectin-1 staining of mucus-producing gastric AD; <b>E</b>, intelectin-1 staining of lung AD; <b>F</b>, calretinin staining of lung AD; <b>G</b>, intelectin-1 staining of lung squamous cell carcinoma (SCC); <b>H</b>, calretinin staining of lung SCC.</p

Expression of intelectin-1 in gastrointestinal goblet cells.

<p>Specimens were immunostained with anti-intelectin-1, and representative photographs are shown here. The scale bar (100 µm) is shown at the bottom of panel A, representatively. The scale bars of panel G (100 µm), panel H (100 µm), panel I (50 µm), and panel J (50 µm) are also shown. The arrows indicate paneth cells. <b>A</b>, duodenum; <b>B</b>, small intestine; <b>C</b>, colon; <b>D</b>, stomach; <b>E</b>, complete intestinal metaplasia (IM) in stomach; <b>F</b>, incomplete IM in stomach; <b>G</b>, hematoxylin–eosin (HE) staining of complete IM in stomach; <b>H</b>, complete IM in stomach; <b>I</b>, mucous granules in goblet cells; <b>J</b>, mucus-secreting goblet cells; <b>K</b>, liver and bile duct (open arrow); <b>L</b>, pancreas and pancreatic duct (open arrows).</p

Expression of intelectin-1 in normal tissues.

<p>Specimens were immunostained with anti-intelectin-1, and representative photographs are shown. A scale bar (100 µm) is shown in panel A, representatively. The scale bars of panel G (100 µm) and panel P (100 µm) are also shown. The closed black arrows indicate intelectin-1-positive cells. <b>A</b>, kidney collecting tubule; <b>B</b>, kidney cortex; <b>C</b>, intelectin-1-negative bladder; <b>D</b>, intelectin-1-positive bladder; <b>E</b>, bronchus. The open arrow shows the serous gland; <b>F</b>, bronchus. The open or closed arrow shows the serous or mucous gland, respectively; <b>G</b>, lung; <b>H</b>, intelectin-1-positive pleura; <b>I</b>, intelectin-1-positive peritoneum; <b>J</b>, intelectin-1-positive tunica vaginalis; <b>K</b>, pericardium; <b>L</b>, cardiac muscle and endocardium; <b>M</b>, vascular; <b>N</b>, S-100 protein staining of adipocytes in greater omentum; <b>O</b>, adipocytes in greater omentum; <b>P</b>, greater omentum with mesothelial cells.</p