A Histological and Clinical Study of MatriDerm® Use in Burn Reconstruction.

Dermal substitutes are well established in the reconstructive ladder. MatriDerm® (Dr. Otto Suwelack Skin & Health Care AG, Billerbeck, Germany) is a single-layer dermal substitute composed of a bovine collagen (type I, III, and V) and elastin hydrolysate, that allows for immediate split-thickness skin grafting (SSG). The aim of this study was to histologically characterize the integration of MatriDerm® when used during burns surgery reconstruction. Eight subjects with nine burn scars and one acute burn wound underwent reconstruction with MatriDerm® and an immediate SSG. MatriDerm® integration and skin graft take were assessed with serial biopsies performed at weeks 1, 2, 3, and 4 and months 2, 3, 6, 9, and 12. Biopsies were assessed with standard special stains and immunohistochemistry, and representative slides were imaged with a transmission electron microscope. Patient satisfaction and clinical scar outcome were assessed with the Vancouver Scar Scale and a patient questionnaire. Histological analysis showed similar stages of wound healing as shown in other dermal templates but on a different timescale. There is early evidence of vascularization and an inflammatory infiltrate in the first 2 weeks. MatriDerm® is resorbed earlier than other dermal substitutes, with evidence of resorption at week 3, to be completely replaced by a neodermis at 2 months. The use of MatriDerm® in reconstruction with immediate skin grafting is supported histologically with early evidence of vascularization to support an epidermal autograft. Future histological studies may help further characterize the ideal dermal substitute.

Oligometastatic deposits of prostate cancer found within the sigmoid pericolic fat that was resected for colonic adenocarcinoma: a case report.

BACKGROUND: Prostate cancer may rarely metastasize to the colon and colonic lymph nodes, and local treatment of oligometastatic deposits may improve oncological outcomes. Immunohistochemical stains are used to determine the most likely source of metastatic deposits when they are seen within surgical specimens. The aim of this case report is to illustrate how such techniques were used to identify unexpected prostatic metastases within the pericolic fat of a sigmoid colon resection specimen following elective curative surgery for colorectal cancer. To our knowledge, this is the first report of complete excision of oligometastatic deposits of prostate cancer found incidentally within the specimen of another cancer. CASE REPORT: An 89-year-old Caucasian man underwent sigmoid colectomy for an obstructing colorectal cancer in the sigmoid colon with some mesenteric lymphadenopathy. He had previously received radical radiotherapy for prostate cancer 10 years earlier. When the specimen was examined by the histopathologist, it was noted that the pericolic fat adjacent to the colorectal adenocarcinoma contained some metastatic deposits. Positive immunohistochemical staining for prostate-specific antigen and prostate-specific acid phosphatase with negative staining for CDX2 and CK20 revealed these to be prostatic metastases rather than colonic. Since these were completely excised, and there were no other metastases, this represented a serendipitous, curative excision of oligometastatic deposits of an additional cancer to the one that was being treated. CONCLUSIONS: This case illustrates how immunohistochemical staining may be used to distinguish the source of metastatic deposits based on the likelihood of primary tumor from a careful and thorough patient history.

Tetraspanin 6 is a regulator of carcinogenesis in colorectal cancer.

Early stages of colorectal cancer (CRC) development are characterized by a complex rewiring of transcriptional networks resulting in changes in the expression of multiple genes. Here, we demonstrate that the deletion of a poorly studied tetraspanin protein Tspan6 in Apcmin/+ mice, a well-established model for premalignant CRC, resulted in increased incidence of adenoma formation and tumor size. We demonstrate that the effect of Tspan6 deletion results in the activation of EGF-dependent signaling pathways through increased production of the transmembrane form of TGF-α (tmTGF-α) associated with extracellular vesicles. This pathway is modulated by an adaptor protein syntenin-1, which physically links Tspan6 and tmTGF-α. In support of this, the expression of Tspan6 is frequently decreased or lost in CRC, and this correlates with poor survival. Furthermore, the analysis of samples from the epidermal growth factor receptor (EGFR)-targeting clinical trial (COIN trial) has shown that the expression of Tspan6 in CRC correlated with better patient responses to EGFR-targeted therapy involving Cetuximab. Importantly, Tspan6-positive patients with tumors in the proximal colon (right-sided) and those with KRAS mutations had a better response to Cetuximab than the patients that expressed low Tspan6 levels. These results identify Tspan6 as a regulator of CRC development and a potential predictive marker for EGFR-targeted therapies in CRC beyond RAS pathway mutations.

MALDI profiles of proteins and lipids for the rapid characterisation of upper GI-tract cancers.

AIM: To identify a reliable MALDI 'cancer fingerprint' to aid in the rapid detection and characterisation of malignant upper GI-tract disease from endoscopic biopsies. METHODS: A total of 183 tissue biopsies were collected from 126 patients with or without oesophago-gastric malignancy and proteins and lipids separated by methanol/chloroform extraction. Peak intensities in the lipid and protein MALDI spectra from five types of samples (normal oesophageal mucosa from controls, normal oesophageal mucosa from patients with oesophageal adenocarcinoma, nondysplastic Barrett's oesophagus, oesophageal adenocarcinoma, normal gastric mucosa and gastric adenocarcinoma) were compared using non-parametric statistical tests and ROC analyses. RESULTS: Normal oesophageal and gastric tissue generated distinct MALDI spectra characterised by higher levels of calgranulins in oesophageal tissue. MALDI spectra of polypeptides and lipids discriminated between oesophageal adenocarcinoma and Barrett's and normal oesophagus, and between gastric cancer and normal stomach. Many down-regulations were unique to each cancer type whilst some up-regulations, most notably increased HNPs 1-3, were common. CONCLUSIONS: MALDI spectra of small tissue biopsies generated with this straightforward method can be used to rapidly detect numerous cancer-associated biochemical changes. These can be used to identify upper GI-tract cancers regardless of tumour location.

Role of endoscopic ultrasound-guided fine-needle aspiration in the diagnosis of solid pancreatic and peripancreatic lesions: is onsite cytopathology necessary?

OBJECTIVES: The reported median diagnostic yield from endoscopic ultrasound (EUS) fine-needle aspiration (FNA) cytology is 78% (range 39-93%). The aim of this study is to describe a single-centre experience in the diagnostic work-up of solid pancreatic and peripancreatic masses without the benefit of an onsite cytopathologist. METHODS: In a consecutive series of 429 EUS examinations performed over a 12-month period by a single operator, 108 were on non-cystic pancreatic or biliary lesions. Data were collected prospectively and the accuracy of FNA was assessed retrospectively using either surgery or repeat imaging as the benchmark in the presence or absence of malignancy. RESULTS: Of the 108 FNAs, 102 (94%) were diagnostic, four were falsely negative (FN) and two were atypical and considered equivocal. There were 78 pancreatic lesions, of which 65 were true positives (TP), 11 true negatives (TN) and two FN, giving an overall accuracy of 97% (76/78). Of nine periampullary lesions, two were TP, six were TN and one was FN, giving an overall accuracy of 89% (8/9). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of EUS-FNA for pancreatic and periampullary lesions combined were 96%, 100%, 100% [95% confidence interval (CI) 95-100%], 85% (95% CI 62-97%) and 97%, respectively. There were 21 bile duct lesions, of which 10 were TP, eight TN, two atypical and one FN, giving an overall accuracy of 86% (18/21). The sensitivity, specificity, PPV, NPV and accuracy of EUS-FNA for biliary lesions were 91%, 100%, 100% (95% CI 69-100%), 91% (95% CI 59-100%) and 95%, respectively. CONCLUSIONS: The diagnostic accuracy of EUS-FNA for pancreatic lesions in our series was 97% and the PPV for the three subgroups of lesion type was 100%; these figures are comparable with the best rates reported in the literature, despite the absence of onsite cytopathology. These rates are potentially a direct result of high-volume practice, dedicated endosonography and cytopathology. These results show that it is possible to achieve high rates of accuracy in places where logistical issues make it impossible to maintain a cytopathologist in the endoscopy suite. In addition, our results contribute to the limited, collective global experience on the effectiveness of EUS-FNA in periampullary and biliary lesions.

Cutaneous presentation of aleukemic monoblastic leukemia cutis - a case report and review of literature with focus on immunohistochemistry.

Aleukemic monoblastic leukemia cutis is a rare cutaneous manifestation of a systemic hematological disorder associated with dermal infiltration of monoblasts preceding bone marrow or peripheral blood involvement. We report a case of a 75-year-old woman who presented with an erythematous maculopapular rash, which was clinically diagnosed as viral exanthema. Microscopy of the skin biopsy showed features of monoblastic leukemia. Her general physical condition rapidly deteriorated and she died 4 weeks later. We present this case to alert dermatologists of innocuous erythematous skin lesions clinically resembling a viral exanthema, which, in rare instances, may be a presenting feature of an aleukemic monoblastic leukemia cutis. This entity poses problems for dermatopathologists even on immunohistochemistry as monoblasts are negative for hemopoietic precursor cell antigens like CD34, Terminal deoxynncleotidy1 transferase (TdT) and CD117.

Morphologic changes in the endometrium associated with the use of the mirena coil: a retrospective study of 106 cases.

This study outlines the histologic changes seen in 106 endometrial specimens after use of the Mirena coil (levonorgestrel) and compares these changes with previous studies. The variables assessed include nature of the endometrial glands, metaplastic glandular changes, nuclear atypia, hobnail change, and endometrial hyperplasia. Stromal changes include pseudodecidualization, mucinous change, ulceration, and infiltration by granulocytes, neutrophils, and plasma cells, and stromal hyaline nodules, a feature not described previously. Additional changes include superficial micropapillary change, infarcted decidua, dystrophic calcification, hemosiderophages, polypoid indentations, cervical microglandular hyperplasia and endocervical pseudodecidualization. These variables are compared with a similar previous study. Significant differences in the incidence of glandular metaplasia, dystrophic calcification, plasma cell infiltrates, hemosiderophages, and presence of nuclear atypia are noted. With increased use of the Mirena coil, histopathologists need to be aware of the characteristic and constant endometrial changes due to progestogenic and mechanical effects, despite a wide variation in the duration of usage.