Proteomic analysis distinguishes basaloid carcinoma as a distinct subtype of nonsmall cell lung carcinoma

The histopathologic type of lung cancer is known to be correlated with tumor behavior and prognosis. However, this classification is subjective and no specific molecular markers have been identified. The aim of this study was to identify protein markers in different types of nonsmall cell lung cancers. Two-dimensional polyacrylamide gel electrophoresis analysis was performed with paired samples of three squamous cell carcinomas, three adenocarcinomas, four large cell carcinomas, and four basaloid carcinomas. We found that 25 proteins in 14 cases of lung cancer were differentially expressed compared to matched nontumorous lung tissues. Among these 25 proteins, 11 proteins were down-regulated and 14 were up-regulated in these four types of lung cancer. Alloalbumin venezia, selenium-binding protein 1, carbonic dehydratase, heat shock 20KD-like protein, and SM22 alpha protein were down-regulated in all 14 cases of lung cancer examined, whereas alpha enolase was consistently up-regulated. Supervised hierarchical cluster analysis based on the 25 differentially expressed proteins showed that basaloid carcinoma formed one independent group, whereas the other three cancer types were not uniquely classifiable. Our findings suggest that basaloid carcinoma is a unique subtype of nonsmall cell lung carcinoma.     

Cytomorphology of the variants of small-cell carcinoma of the lung

Cytologic classification of subtypes of small-cell carcinoma of the lung (SCCL) was retrospectively performed on respiratory material of 90 cases of lung carcinoma cytologically diagnosed as SCCL. Additionally, the cytologic material was reexamined for the presence of variants of SCCL in 68 cases of lung carcinoma whose types had not been conclusively defined by cytology. The type of lung cytology specimens reviewed were sputa, bronchial washings and brushings and fine needle aspirations. The study included review of pretreatment tumor histology, when present, and examination of the ultrastructure of the tumor in selected cases whose type had not been well defined by histology. Subtype recognition depended on the adequacy of the specimens rather than on the type of cytologic material examined. The cytologic subtyping was generally in agreement with the histologic subtyping of the tumor, except for cases in which SCCL was combined with other types of lung carcinoma, where certain discrepancies were noted.     

Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

Brachydactyly ("short digits") is a general term that refers to disproportionately short fingers and toes, and forms part of the group of limb malformations characterized by bone dysostosis. The various types of isolated brachydactyly are rare, except for types A3 and D. Brachydactyly can occur either as an isolated malformation or as a part of a complex malformation syndrome. To date, many different forms of brachydactyly have been identified. Some forms also result in short stature. In isolated brachydactyly, subtle changes elsewhere may be present. Brachydactyly may also be accompanied by other hand malformations, such as syndactyly, polydactyly, reduction defects, or symphalangism. For the majority of isolated brachydactylies and some syndromic forms of brachydactyly, the causative gene defect has been identified. In isolated brachydactyly, the inheritance is mostly autosomal dominant with variable expressivity and penetrtance. Diagnosis is clinical, anthropometric and radiological. Prenatal diagnosis is usually not indicated for isolated forms of brachydactyly, but may be appropriate in syndromic forms. Molecular studies of chorionic villus samples at 11 weeks of gestation and by amniocentesis after the 14^th week of gestation can provide antenatal diagnosis if the causative mutation in the family is known. The nature of genetic counseling depends both on the pattern of inheritance of the type of brachydactyly present in the family and on the presence or absence of accompanying symptoms. There is no specific management or treatment that is applicable to all forms of brachydactyly. Plastic surgery is only indicated if the brachydactyly affects hand function or for cosmetic reasons, but is typically not needed. Physical therapy and ergotherapy may ameliorate hand function. Prognosis for the brachydactylies is strongly dependent on the nature of the brachydactyly, and may vary from excellent to severely influencing hand function. If brachydactyly forms part of a syndromic entity, prognosis often depends on the nature of the associated anomalies.     

Nevoid basal cell carcinoma

The use of computer technology is becoming increasingly important in the handling of medical records. The cardiology data system used at The Hospital for Sick Children has greatly simplified the review and analysis of patient records. The methods of capturing data are logical and straightforward and have assisted fellows, residents and students in learning the systematic approach to the diagnosis of heart disease in children. The review of particular defects conducted as a research project has often led to further studies which have made important contributions to the knowledge of heart disease in childhood.     

Cytomorphology of primary small-cell (Merkel-cell) carcinoma of the skin in fine needle aspirates

The histologic appearance of primary small-cell carcinoma of the skin (the so-called Merkel-cell tumor) is similar to other small-cell tumors that may metastasize to the dermis. Significance has been placed on the electron microscopic appearance of this tumor since the ultrastructural features of this neoplasm are helpful in distinguishing it from most of the other neoplasms considered in the differential diagnosis. To determine whether any additional morphologic criteria might exist to distinguish this neoplasm, the fine needle aspirate appearance of a primary small-cell carcinoma of the skin was studied and compared to that of similar preparations of other small-cell tumors that could potentially involve the dermis. Cells of this unusual tumor were round and showed neither cohesiveness nor nuclear molding. Mitoses were numerous. The chromatin pattern was bland. The cytologic features of this tumor can aid in the distinction of primary small-cell carcinoma of the skin from other metastatic small-cell neoplastic lesions in the dermis of adults.     

Cytomorphology and copper content of the basal cells in the midgut gland of Nautilus (Cephalopoda,Tetrabranchiata)

Summary By means of light and electron microscopical studies on Nautilus pompilius and Nautilus macromphalus, special basal cells within the alveolary enlarged terminal parts of the tubules of the midgut gland were revealed. Their abundant rough endoplasmic reticulum (RER) with enlarged cisterns synthesizes ring-shaped macromolecules that resemble the hemocyanin molecules within the bloods-paces in size and form and seem to be secreted throughout the lamina basalis, locally discharged into the adjacent blood sinus. The hypothesis that this cell type represents a site of hemocyanin synthesis was confirmed by Zeeman AAS and ASTEM analyses of the content and distribution of copper within the glandular tissue, especially the different compartments of this cell type.     

Deep-seated rectal/anal basaloid carcinoma: useful immunocytochemistry in rare squamous cell carcinoma variants

Objectives:  To report the cytological aspects of ano-rectal basaloid carcinoma (BC) variant in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) conventional and liquid-based cytology (LBC), in a series of 10 cases of deep-seated squamous cell carcinomas (SCC), and to discuss the diagnostic difficulties in interpreting the morphology and immunocytochemical findings.
Methods:  Ten cases of EUS-FNA smears and LBC specimens of deep-seated pelvic masses were retrospectively collected from January 2001 to November 2006.
Results:  Ten EUS-FNA specimen cases were SCC, eight corresponding to usual SCC and two to BC-variant. Of these two cases, only one was correctly diagnosed by EUS-FNA specimen, whereas in the second case, the initial cytological diagnosis was poorly differentiated adenocarcinoma and the final diagnosis of basaloid carcinoma variant was established on surgical resection. Immunocytochemistry (ICC) using CK7, CK20 and CK34βe12 on FNA specimens confirmed the diagnosis retrospectively.
Conclusion:  The diagnosis of basaloid variant of SCC in a rectal location can be very difficult, both on account of the uncommon location and because of the low specificity of morphological aspects on EUS-FNA smears. The immunocytochemical technique, including a limited spectrum of keratins (CK7, CK20, CK34βe12, and p63) is necessary to avoid this diagnostic pitfall.     

Programmed cell death 1 (PDCD1) gene haplotypes and susceptibility of patients to basal cell carcinoma

Molecular Biology Reports - Programmed death-1 (PD-1), as an immunoinhibitory receptor encoded by programmed cell death-1 (PDCD1) gene, has a pivotal role in tolerance to self-antigens. Mutations...     

Liver kinase B1 (LKB1) in the pathogenesis of UVB-induced murine basal cell carcinoma

LKB1, a known tumor suppressor, is mutated in Peutz–Jeghers Syndrome (PJS). It is responsible for the enhanced cancer risk in patients with PJS. Dysregulation of LKB1-dependent signaling also occurs in various epithelial cancers. UVB alters the expression of LKB1, though its role in the pathogenesis of skin cancer is unknown. Here we describe upregulation of LKB1 expression in UVB-induced murine basal cell carcinoma (BCC) and in human skin tumor keratinocytes. AMP-kinase and acetyl Co-A carboxylase, the downstream LKB1 targets, are also enhanced in this neoplasm. In addition, p-Akt, a kinase which inactivates GSK3β by its phosphorylation, is enhanced in BCCs. Consistently, an accumulation of p-GSK3β and an increase in activated nuclear β-catenin are found. mTOR signaling, which is also inhibited by LKB1, remains upregulated in BCCs. However, a marked decrease in the expression of sestrins, which function as potent negative regulators of mTOR is observed. Metformin, a known chemical inducer of this pathway, was found effective in immortalized HaCaT keratinocytes, but failed to activate the LKB1-dependent signaling in human carcinoma A431 cells. Thus, our data show that the LKB1/AMPK axis fails to regulate mTOR pathway, and a complex regulatory mechanism exists for the persistent mTOR activation in murine BCCs.     

Histologic study of recurrent basal cell carcinoma

This retrospective study of recurrent basal cell carcinoma suggests the presence of irregularity in the peripheral palisade (IPP), squamous differentiation (SD), and tumor ulceration as histologic criteria for the recurrent tumor and the presence of infiltrates of small lymphocytes (LI) in the tumor as a criterion of tumor-directed host immunocompetence. The presence of either irregularity in the peripheral palisade in greater than 75 percent of the tumor cords or absence of infiltrates of small lymphocytes at the tumor base were each significant at the p less than 0.001 level in characterizing recurrent basal cell carcinoma.