Microcystic adnexal carcinoma (sclerosing sweat duct carcinoma)

Microcystic adnexal carcinoma (MAC) is a recently described malignant neoplasm of the adnexal structures of skin that shows a marked propensity for early infiltrative and locally aggressive growth. Its banal clinical appearance may lead to a delay in diagnosing the tumor by biopsy, and its multifaceted histologic features may lead to an incorrect tissue diagnosis. Confusion with benign tumors and less aggressive malignancies can lead to inadequate initial treatment and extensive recurrences. We describe three cases of microcystic adnexal carcinoma and review the clinical and histologic features, treatment, and prognosis of this neoplasm.     

Immune surveillance of nasopharyngeal carcinoma (NpC)

In the U.S., nasopharyngeal carcinoma (NpC) kills >7,600 each year. Deaths are predominantly among adult men, and in most cases, early detection and treatment can save lives. Despite the annual spending of approximately 3.2 billion dollars on head and neck cancer research, NpC remains a neglected disease since its fatality rates are among the lowest nation wide. The relative survival rates from NpC have not improved in the U.S. in the last 20 years. Infection with Epstein Barr Virus (EBV) is an important co-factor in the etiology of NpC. In other regions of the word (e.g., South-East Asia, Latin America), EBV infection and NpCrelated prevalence and mortality are substantially higher and more alarming. Epidemiological data indicate high prevalence of EBV infection and increased risk for NpC among Central and South American and Asian immigrants in the U.S., and also predict a sharp increase in NpC incidence in the next decade. To face this emerging threat, it is important to develop and validate novel modes of detection and intervention for NpC. To this end, we characterized the proteomic signature of NpC, and of the tumor infiltrating lymphocytes of the CD8+, activated (CD38+, mTOR+) and regulatory immune cell (FoxP3+) phenotype. Paraffinized biopsies were processed, and tissue microarrays constructed and tested by immunohistochemistry and triimmunohistofluorescence for a battery of signaling markers, including AKT and PI3K, in conjunction with EBV status and ANKRD11, an NpC susceptibility biomarker. Microphotographs, analyzed and quantified by confocal microscopy and fractal analysis, suggest new avenues for immunotherapies of NpC.     

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.     

Sarcomatoid hepatocellular carcinoma (SHC): a case report

Background

Sarcomatoid hepatocellular carcinoma (SHC) is a rare malignant hepatic tumor. Recurrent interventional therapies such as transcatheter arterial chemo-embolization (TACE), radiofrequency ablation (RFA), and percutaneous ethanol injection have been reported previously utilized in a majority of SHC cases. To date, the exact pathogenic mechanisms underlying sarcomatoid transformation of hepatocellular carcinoma (HCC) remain unknown.

Case presentation

In this study, we report a 68-year-old female SHC patient admitted to our hospital due to discrete abdominal distention for more than 20 days. Abdominal computed tomography (CT) with tri-phase enhancement revealed portal vein tumor thrombi (PVTT) and a left hepatic lobe lesion measuring 110.0 mm?×?160.0 mm. The patient subsequently underwent liver resection, after which pathological examination revealed proliferation of spindle-shaped SHC cells. A sarcomatoid, T4 stage carcinoma was eventually diagnosed. Forty-seven days after the operation, tri-phase enhanced CT detected extensive lesions in the liver, spleen, peritoneum, omentum majus, and mesentery, indicating SHC recurrence and metastases. Combination chemotherapy with pirarubicin and cisplatin was initiated for 1 cycle, but terminated due to resultant severe myelosuppression and medication intolerance. The patient was lost to therapy after 3 months of follow-up.

Conclusions

This case is unique because of hepatitis C virus infection. We should consider the possibility of this disease in patients with atypical clinical presentation.

     

Hepatocellular carcinoma in a squirrel monkey (Saimiri sciureus)

Abstract: A well-differentiated hepatocellular carcinoma of the liver was diagnosed in a female squirrel monkey. The lesion showed trabecular, solid and glandular features that are characteristics of malignant liver tumours.     

Neuroendocrine carcinoma of the skin (Merkel cell carcinoma): immunocytochemical study of a case

The immunocytochemical phenotype was evaluated in a case of Merkel cell carcinoma of the skin. Intermediate filaments, i.e. neurofilament, glial fibrillary acid protein, cytokeratins, keratin and panfilament as well as S-100 protein, calcitonin and epithelial membrane antigen were detected by immunoperoxidase methods. Nodular positivity for neurofilament was observed. The remaining intermediate filaments and other markers were negative. Thus the origin of Merkel cell carcinoma appears uncertain and this tumor probably has neuroendocrine activity.     

Elevated expression of squamous cell carcinoma antigen (SCCA) is associated with human breast carcinoma

Squamous cell carcinoma antigen (SCCA) belongs to the serine protease inhibitor (Serpin) family of proteins. Elevated expression of SCCA has been used as a biomarker for aggressive squamous cell carcinoma (SCC) in cancers of the cervix, lung, head and neck, and liver. However, SCCA expression in breast cancer has not been investigated. Immunohistochemical analysis of SCCA expression was performed on tissue microarrays containing breast tumor tissues (n = 1,360) and normal breast epithelium (n = 124). SCCA expression was scored on a tiered scale (0-3) independently by two evaluators blind to the patient''s clinical status. SCCA expression was observed in Grade I (0.3%), Grade II (2.5%), and Grade III (9.4%) breast cancers (p<0.0001). Comparing tissues categorized into the three non-metastatic TNM stages, I-III, SCCA positivity was seen in 2.4% of Stage I cancers, 3.1% of Stage II cancers, and 8.6% of Stage III breast cancers (p = 0.0005). No positive staining was observed in normal/non-neoplastic breast tissue (0 out of 124). SCCA expression also correlated to estrogen receptor/progesterone receptor (ER/PR) double-negative tumors (p = 0.0009). Compared to SCCA-negative patients, SCCA-positive patients had both a worse overall survival and recurrence-free survival (p<0.0001 and p<0.0001, respectively). This study shows that SCCA is associated with both advanced stage and high grade human breast carcinoma, and suggests the necessity to further explore the role of SCCA in breast cancer development and treatment.     

High-affinity binding sites for 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE) in carcinoma cells.

12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE) enhances tumor cell adhesion to endothelial cells [Honn et al. (1988) Proc. Soc. Exp. Biol. Med. 189, 130-135]. The effect is correlated to surface expression of an integrin receptor, GpIIb/IIIa. Here, we describe evidence for high-affinity binding of 12(S)-HETE to Lewis lung carcinoma cells. Scatchard plot analyses indicated a single class of sites with apparent Kd and Bmax values of 0.44 nM and 66,000 sites per cell, respectively. Competition experiments with unlabeled compounds shod d that the binding was reversible and saturable as well as stereo- and regiospecific. The 12(S)-HETE binding, demonstrated here, might be an important step in a series of events controlling surface expression of integrin receptors.     

Lymphokine-activated suppressor (LAS) cells in patients with gastric carcinoma

Summary T-cell-growth-factor (TCGF) activated peripheral blood lymphocytes (PBL), cultured for 14 days, showed killer cell activities against natural-killer resistant Daudi cells in a 4 h ⁵¹Cr-release assay. However, the effector cells obtained from patients with nonresectable carcinoma exhibited very much lower cytotoxicity to tumor cells. To analyze the mechanism of depression, we have attempted to examine suppressor cell activities of the TCGF-activated PBL. The assay for the suppressor cell activities was made by in vitro inhibition of cell-mediated cytotoxicity by incubating radiolabeled target tumor cells with lymphokine-activated killer (LAK) cells and TCGF-activated PBL. LAK cells were induced by cultivation with recombinant interleukin-2. TCGF-activated PBL, obtained from four out of ten patients with resectable carcinoma and nine out of ten patients with nonresectable carcinoma, significantly suppressed the LAK cell activities. However, this suppression was not observed in TCGF-activated PBL from ten normal healthy control subjects. TCGF-activated PBL with immunosuppressive reactivity were named lymphokine-activated suppressor (LAS) cells. To investigate the phenotypic characterization of TCGF-activated PBL, the cells were analyzed by two-color flow cytometry. TCGF preferentially expanded CD8⁺CD11^– cells and decreased the growth of CD8⁺CD11⁺ cells in both normal healthy control subjects and gastric cancer (resectable and nonresectable) patients. Dominantly expressed CD8⁺CD11^– cells on TCGF-activated PBL in patients — especially those with nonresectable gastric carcinoma — showed strong LAS cell activity, irrespective of the presence of killer cell activities of CD8⁺CD11^– cells in TCGF-activated PBL from normal healthy control subjects. The results suggested the generation of CD8⁺CD11^– LAS cells from cancer patients, and revealed that CD8⁺CD11^– T-cells contained killer and/or suppressor cell function. In addition, it was found that the TCGF-activated PBL from gastric cancer patients were associated with an increased proportion of CD4⁺Leu8⁺, HLA-DR⁺CD8⁺ and HLA-DR⁺CD25⁺ cells.Abbreviations LAK lymphokine-activated killer - TCGF T-cell growth factor - PBL peripheral blood lymphocytes - rIL-2 recombinant interleukin-2 - LAS lymphokine-activated suppressor This study was supported by a grant-in-aid for scientific research (no. 62570307) from the Ministry of Education, Science and Culture, Japan     

Hepatic neuroendocrine carcinoma in a Japanese macaque (Macaca fuscata)

Primary neuroendocrine neoplasm of the liver is extremely rare in both humans and non‐human primates. The present report describes the clinical and pathological findings of an aged Japanese macaque (Macaca fuscata) with hepatic neuroendocrine carcinoma. To our knowledge, this is the first report of hepatic neuroendocrine neoplasm in macaques.     

Iron-induced oxidative damage in colon carcinoma (Caco-2) cells

Intestinal epithelial cells have an active apical iron uptake system that is involved in the regulated absorption of iron. By the action of this system, intestinal cells acquire increasing amounts of iron with time. Since intracellular reactive iron is a source of free radicals and a possible cause of colon carcinoma, this study analyzed the oxidative damages generated by iron accumulation in Caco-2 cells. Cells cultured with increasing concentrations of iron increased both total intracellular iron and the reactive iron pool, despite an active IRE/IRP system, which regulates intracellular iron levels. Increasing concentrations of iron resulted in increased protein oxidative damage, as shown by the immunoreactivity for 4-hydroxy-2-nonenal-modified proteins, and markedly induced DNA oxidation determined by 8-hydroxy-2'-deoxyguanidine production. Iron also impaired cell viability, resulting in increased cell death after 6 days of culture. In summary, iron accumulation by intestinal Caco-2 cells correlated with oxidative damage to proteins and DNA. Oxidative damage finally resulted in loss of cell viability. The Fe-induced oxidative damage observed may be relevant in understanding the cascade of events associated with iron-mediated colon carcinogenesis.