BackgroundThe clear cell/signet-ring cell variant of cutaneous squamous cell carcinoma (cSCC) is extremely rare. Its carcinogenesis has consistently been linked to ultraviolet radiation and HPV in the literature. However, there is little definite information about the contribution of diabetes mellitus (DM) to cSCC.Case presentationA 78-year-old Chinese woman with type 2 DM presented with a mushroom-like lump in her right thigh. Histological findings revealed that the lesion was mainly composed of clear cells and signet-ring cells. The septa of vacuoles in cytoplasm displayed positivity for periodic acid schiff (PAS) and cytokeratins such as AE1/AE3, CK5/6, CK14, and CK19. Malignant cells did not express CK7, CK8, CK18, CK20, p16, p53, or c-erbB-2, and the Ki-67 index was less than 5 %. We further explored the etiology of clear cell/signet-ring cell cSCC using human papillomavirus (HPV) type-specific PCR and genotyping and confirmed that the patient was not infected with HPV. Nucleus positivity for p63 indicated the involvement of the p53 family in the lesion. Meanwhile, the expression of fibroblast growth factor receptor-2 (FGFR2), a downstream effector of p63, was upregulated in tumor cells.ConclusionsThis study provides the first report on the clear cell/signet-ring cell variant of cSCC found in the right thigh of a patient with type 2 DM. Metabolic imbalance in addition to conventional pathogens such as UV and HPV may contribute to the development of the lesion via p63/FGFR2 axis.

Let R 3 1 be the Lorentzian 3-space with inner product ( , ). Let Q 3 be the conformal compactification of R 3 1 , obtained by attaching a light-cone C∞ to R 3 1 in infinity. Then Q 3 has a standard conformal Lorentzian structure with the conformal transformation group O(3, 2)/{±1}.In this paper, we study local conformal invariants of time-like surfaces in Q 3 and dual theorem for Willmore surfaces in Q 3 . Let M ⊂ R 3 1 be a time-like surface. Let n be the unit normal and H the mean curvature of the surface M . For any p ∈ M we define S 21 , which has the same tangent plane and mean curvature as M at the point p. We show that the family {S 2 1 (p), p ∈ M } of hyperboloid in R 3 1 defines in general two different enveloping surfaces, one is M itself, another is denoted byM (may be degenerate), and called the associated surface of M . We show that (i) if M is a time-like Willmore surface in Q 3 with non-degenerate associated surfaceM , thenM is also a time-like Willmore surface in Q 3 satisfyinĝ M = M ; (ii) ifM is a single point, then M is conformally equivalent to a minimal surface in R 3 1 .

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a highly aggressive and extremely rare hematologic disease with a poor prognosis, involving mainly the skin and bone marrow. The immunophenotype of these tumor cells is characterized by the expression of CD4, CD56, CD123, TCL-1, and CD303. To date, no consensus has been reached on the standard of care for BPDCN. Currently, clinical treatment is mainly based on high-dose chemotherapy combined with hematopoietic stem cell transplantation. However, this treatment method has limitations for elderly, frail, and relapsed/refractory patients. In recent years, breakthroughs in molecular biology and genetics have not only provided new ideas for the diagnosis of BPDCN but also helped develop targeted treatment strategies for this disease. The emergence of targeted drugs has filled the gap left by traditional therapies and shown great clinical promise. This article focuses on the latest advances in genetics and targeted therapies for BPDCN, especially the emerging therapies that may provide new ideas for the clinical treatment of BPDCN.Abbreviations: 5-Aza = 5-azacytidine, ALL = acute lymphoblastic leukemia, allo = allogeneic, AML = acute myeloid leukemia, BETi = bromodomain and extra-terminal protein inhibitors, BPDCN = blastic plasmacytoid dendritic cell neoplasm, CAR = chimeric antigen receptor, CR1 = first complete remission, FDA = Food and Drug Administration, HSCT = hematopoietic stem cell transplantation, IL-3 = interleukin-3, LXR = liver X receptor, R/R = relapsed/refractory, SL-401 = tagraxofusp.

BACKGROUND Synchronous multiple primary cancers (SMPC) mean two or more malignant tumors occurring simultaneously and with different origins no matter what types they are or where they are located. The carcinogenesis of SMPC often involves variations of some specific genes. However, the correlation between CDH1 mutations and synchronous multiple primary gastrointestinal cancers is largely unknown. CASE SUMMARY A 62-year-old woman had sustained abdominal pain for one week and visited our hospital. Gastrointestinal endoscopy revealed multiple small polypoid lesions in both the stomach and colorectum. Computed tomography and laboratory results were within normal limits. Pathological evaluation confirmed signet ring cell carcinoma without obvious metastatic evidence. Malignant cells showed negativity for E-cadherin and positivity for β-catenin in the cytoplasm and nucleus. DNA sequencing performed on paraffin-embedded tissue revealed two exactly coincident alterations in CDH1 , C.57T>G and C.1418A>T . CONCLUSION This case suggests that the combination of CDH1 mutations and WNT/β-catenin signaling activation contributes to the carcinogenesis of gastrointestinal SMPC.

BackgroundThe origin and heterogeneity of hepatic progenitor cells (HPCs) remain unclear. This study aimed to investigate the involvement of epithelial-mesenchymal transition (EMT) in the histogenesis of HPCs.MethodsSurgical liver specimens from patients with HBV-related hepatitis and cirrhosis were investigated with double immunofluorescence labeling to detect antigens associated with HPCs and EMT. Ductular reactions were subjected to quantitative reverse transcription PCR following isolation by laser capture microdissection. Electron microscopic examination was performed to find an ultrastructural evidence of EMT.ResultsThe number of EpCAM-positive HPCs was proportional to the disease severity. The S100A4 expression of HPCs was firstly observed in mild hepatitis and increased significantly in moderate hepatitis, but decreased in severe hepatitis and cirrhosis. The levels of MMP-2, Twist, and Snail increased in direct proportion to the number of HPCs. Some hepatocytes adjacent to portal tracts in cirrhosis showed positivity for MMP-2. Although CK7 and E-cadherin levels decreased in mild and moderate hepatitis, HPCs re-expressed both of them in severe hepatitis and cirrhosis. However, HPCs expressed neither vimentin nor αSMA. The relative mRNA expression levels of EpCAM and EMT-associated markers supported immunohistochemical results. Electron microscopic examination demonstrated the existence of intercellular junctions among HPCs, cholangiocytes, and intermediate hepatocyte-like cells.ConclusionWe provided preliminary evidence for the involvement of EMT in the histogenesis of HPCs from cholangiocytes in HBV-related liver diseases. HPCs may re-transdifferentiate into hepatocytes, and the differentiation direction depends, at least in part, on interactions between HPCs and the surrounding microenvironment, especially the non-resolving inflammation caused by HBV infection.