Florid Mesothelial Hyperplasia Associated with Abdominal Wall Endometriosis Mimicking Invasive Carcinoma

Florid mesothelial hyperplasia typically occurs in the pelvis, abdomen, or chest associated with an underlying neoplastic or inflammatory process. These lesions are of clinical significance because they can mimic a neoplasm. Early reports were published in the 1970s, but only a few case series of such lesions have been published in the gynecologic pathology literature. Here, we report a case of florid mesothelial hyperplasia with an infiltrative growth pattern, mimicking an invasive carcinoma. The lesion was associated with endometriosis forming a mass lesion in the abdominal wall. Histologically, tubular arrangements and nests of mesothelial cells, some with artifactual slit-like spaces, formed a stellate lesion adjacent to endometrial glands and stroma. Cytologic atypia was mild and reactive, and positive immunostaining for calretinin, WT-1, and cytokeratin 5 identified the lesion as mesothelial and benign. We describe in detail the histologic findings in this case and review the pertinent literature. We discuss the clinically importance of this diagnostic pitfall and the path to arriving at the correct diagnosis.

Cytokeratin 5 and cytokeratin 6 expressions are unconnected in normal and cancerous tissues and have separate diagnostic implications

Cytokeratins (CKs) 5 and 6 are functionally unrelated but often analyzed together using bispecific antibodies in diagnostic immunohistochemistry. To better understand the diagnostic utility of CK5 or CK6 alone, tissue microarrays with > 15,000 samples from 120 different tumor types as well as 608 samples of 76 different normal tissues were analyzed by immunohistochemistry. In normal tissues, both CKs occurred in the squamous epithelium; CK5 dominated in basal and CK6 in suprabasal layers. CK5 (not CK6) stained basal cells in various other organs. Within tumors, both CK5 and CK6 were seen in > 95% of squamous cell carcinomas, but other tumor entities showed different results: CK5 predominated in urothelial carcinoma and mesothelioma, but CK6 in adenocarcinomas. Joint analysis of both CK5 and CK6 obscured the discrimination of epithelioid mesothelioma (100% positive for CK5 alone and for CK5/6) from adenocarcinoma of the lung (12.8% positive for CK5 alone; 23.7% positive for CK5/6). CK5 and CK6 expressions were both linked to high grade, estrogen receptor, and progesterone receptor negativity in breast cancer (p < 0.0001 each), grade/stage progression in urothelial cancer (p < 0.0001), and RAS mutations in colorectal cancer (p < 0.01). Useful diagnostic properties which are commonly attributed to CK5/6 antibodies such as basal cell staining in the prostate, distinction of adenocarcinoma of the lung from squamous cell carcinoma and epithelioid mesothelioma, and identification of basal-type features in urothelial cancer are solely driven by CK5. At least for the purpose of distinguishing thoracic tumors, monospecific CK5 antibodies may be better suited than bispecific CK5/6 antibodies.

Inhibition of Notch activity promotes pancreatic cytokeratin 5-positive cell differentiation to beta cells and improves glucose homeostasis following acute pancreatitis

Some individuals develop prediabetes and/or diabetes following acute pancreatitis (AP). AP-induced beta-cell injury and the limited regenerative capacity of beta cells might account for pancreatic endocrine insufficiency. Previously, we found that only a few pancreatic cytokeratin 5 positive (Krt5+) cells differentiated into beta cells in the murine AP model, which was insufficient to maintain glucose homeostasis. Notch signaling determines pancreatic progenitor differentiation in pancreas development. This study aimed to examine whether Notch signaling inhibition could promote pancreatic Krt5+ cell differentiation into beta cells and improve glucose homeostasis following AP. Pancreatic tissues from patients with acute necrotizing pancreatitis (ANP) were used to evaluate beta-cell injury, Krt5+ cell activation and differentiation, and Notch activity. The murine AP model was induced by cerulein, and the effect of Notch inhibition on Krt5+ cell differentiation was evaluated both in vivo and in vitro. The results demonstrated beta-cell loss in ANP patients and AP mice. Krt5+ cells were activated in ANP pancreases along with persistently elevated Notch activity, which resulted in the formation of massive duct-like structures. AP mice that received Notch inhibitor showed that impaired glucose tolerance was reversed 7 and 15 days following AP, and increased numbers of newborn small islets due to increased differentiation of Krt5+ cells to beta cells to some extent. In addition, Krt5+ cells isolated from AP mice showed increased differentiation to beta cells by Notch inhibition. Collectively, these findings suggest that beta-cell loss contributes to pancreatic endocrine insufficiency following AP, and inhibition of Notch activity promotes pancreatic Krt5+ cell differentiation to beta cells and improves glucose homeostasis. The findings from this study may shed light on the potential treatment of prediabetes/diabetes following AP.

A RARE HISTOLOGICAL FINDING AFTER PANCREATICODUODENECTOMY

In this paper, we describe the case of successful surgical treatment of a rare combination of three malignant tumors of the major duodenal papilla in one patient. A 59-year-old woman presented with abdominal pain, fever, nausea, vomiting, weight loss and obstructive jaundice. After routine examination, the patient with suspected cancer of the major duodenal papilla underwent pylorus-sparing pancreatoduodenal resection. Final histology revealed a rare collision of three types of cancer in the major duodenal papilla invading the pancreatic head: moderately-differentiated adenocarcinoma (30 %), moderately differentiated squamous cell carcinoma (20 %) and poorly differentiated small cell neuroendocrine cancer (50 %), surgical resection margins were intact. Immunohistochemical analysis revealed positivity for synaptophysin, chromogranin A and cytokeratin 5/6. The tumor diameter of 2 cm and the absence of signs of locoregional spread allowed the process to be staged as T2N0M0, so the patient did not receive any adjuvant treatment. Follow-up CT performed 6 months later showed two lesions in the liver, and biopsy of one of them was performed. Metastasis of neuroendocrine cancer was histologically and immunohistochemically verified. She started first-line chemotherapy with etoposide + cisplatin.

Basal cell carcinoma with signet ring cell morphology accumulating the ubiquitinated cytokeratin 5/6

Basal cell carcinoma (BCC) showing signet ring (SR) cell morphology is a very rare variant of BCC. Here, we report BCC with SR cell morphology developed in the right cheek skin of a 79-year-old man. Histopathologic examination showed irregularly shaped islands of basaloid cells with characteristic peripheral palisading. Inside of the cancer islands, many tumour cells showed an enlarged fine granular cytoplasm with the peripherally compressed nuclei, being similar to the SR cell. Immunohistochemical examination revealed dense accumulation of cytokeratin (CK) 5/6 and a faint signal of 34βE12 in SR cells. The reported myoepithelial markers were not detected. Interestingly, ubiquitin, a component of the ubiquitin–proteasome protein degradation system, was co-localised in the SR cells. These suggest, for the first time, that accumulation of the undegraded CK5/6 with ubiquitination results in the SR cell morphology. Our report showed that the aberrant keratin turnover is associated with the SR cell BCC.