ABSTRACT
The prognostic value of microsatellite instability (MSI), as well as other histological characteristics such as lymphovascular invasion (LI), perineural invasion (PNI) and extramural vascular invasion (EMVI), is unclear in colorectal mucinous carcinoma (MC). This study aims to determine the relevance of these factors in MC patients and analyses the role of MSI in stage III MC patients treated with adjuvant chemotherapy. A cohort of 650 patients diagnosed with stages I-IV colonic MC from 2000 to 2010 was selected from PALGA, the nationwide Dutch pathology databank. Histopathology was revised and mismatch repair (MMR) status determined. Univariate and multivariate survival analyses were performed. Deficient MMR (dMMR) was found in 33% of MCs and correlated with female gender and right-sidedness, but also with lower tumour stage (stages I/II: 73.2 versus 47%; P < 0.0001) and the absence of EMVI (9.7 versus 23.7%; P < 0.0001) and PNI (5.6 versus 12.7%; P = 0.005). On univariate analysis OS was better for dMMR MC than for proficient MMR (pMMR) MC (median OS of 9.7 versus 5.0 years; P = 0.009), but MMR status was no longer a relevant prognostic factor on multivariate analysis [hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.70-1.18]. Stage III MC patients benefited from adjuvant chemotherapy, and dMMR status was associated with better OS in this group (HR = 0.35, 95% CI = 0.13-0.94). EMVI, LI and PNI, but not MMR, status are independent prognostic factors for survival in MC patients. Stage III MC patients benefit from adjuvant chemotherapy and dMMR status is associated with improved survival when adjuvant chemotherapy is given.
Subject(s)
Colonic Neoplasms , Research Design , Female , Humans , Colonic Neoplasms/genetics , PrognosisABSTRACT
AIM: Mucinous carcinoma is a histological subtype of rectal cancer and has been associated with a poor response to neoadjuvant chemoradiotherapy (CRT). The primary aim of this study was to analyse the response on MRI of mucinous locally advanced rectal cancer (LARC) after CRT compared to regular adenocarcinoma. METHOD: Patients with LARC (defined as cT4 and/or cN2), who underwent CRT followed by restaging MRI and surgery in two tertiary referral hospitals were retrospectively included in the study. Pre- and post-treatment MRI was reviewed by an experienced abdominal radiologist. RESULTS: A total of 102 patients, of whom 29 were diagnosed with mucinous carcinoma, were included for analysis. At restaging MRI, adenocarcinoma patients demonstrated significantly less clinical involvement of the mesorectal fascia (37% vs. 62%, P = 0.003) while this was not demonstrated in mucinous carcinoma patients (86% vs. 97%, P = 0.16). Significant downstaging after CRT in adenocarcinoma patients (P = 0.01) was seen while, in mucinous carcinoma patients, no downstaging after CRT (P = 0.89) was seen. Pathology revealed significantly higher rates of an involved circumferential resection margin in mucinous carcinoma versus adenocarcinoma patients (27.6% vs. 1.4%; P < 0.001). After multivariate regression analysis, mucinous carcinoma remained an independent prognostic factor for local recurrence (hazard ratio 3.6; 95% CI 1.1-12.4), although no differences in overall or disease-free survival were observed. CONCLUSION: Mucinous rectal carcinoma is associated with a poor clinical response at restaging MRI after CRT, leading to relatively higher rates of involved circumferential resection margins at pathology. In this cohort, mucinous carcinoma seems to be a prognostic factor for increased risk of local recurrence, without an effect on overall survival.
Subject(s)
Neoplasm Recurrence, Local , Rectal Neoplasms , Chemoradiotherapy , Humans , Magnetic Resonance Imaging , Neoadjuvant Therapy , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/therapy , Neoplasm Staging , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND AND AIMS: There is no clear guideline nor protocol for macroscopic examination of the gallbladder, leaving surgeons extemporaneous in regard of gallbladder examination in selective histopathologic policy. The purpose of this article is to describe a surgical approach for adequate macroscopic inspection of the gallbladder. MATERIALS AND METHODS: The described practical method was developed in collaboration between surgeons and pathologists. This method was introduced in 2011 and implemented in 2012. We retrospectively reviewed the number of cholecystectomies and number of histopathologic examinations between 2006 and 2017, using our own patient database. We used the Netherlands Cancer Registry (NCR) to examine the incidence of gallbladder cancer patients before and after implementation of the selective policy in our hospital. In addition to the method, we depict several frequent macroscopic abnormalities in order to provide some examples for surgical colleagues. RESULTS: Since implementation of the selective policy, 2271 surgical macroscopic gallbladder examinations were performed. As a result, we observed a significant decrease from 83% in 2012 to 38% in 2017, in histopathologic examination of the gallbladder following cholecystectomy. We observed a stable trend of gallbladder carcinoma in the same period (0.17%, n = 4 during 2006-2011 and 0.26%, n = 6 during 2012-2017). CONCLUSION: A simple, valid and easy method is described for future macroscopic analysis by the surgeon following a cholecystectomy.
Subject(s)
Cholecystectomy , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/surgery , Gallbladder/pathology , Databases, Factual , Gallbladder/surgery , Humans , Netherlands , Retrospective StudiesABSTRACT
INTRODUCTION: Neuroendocrine neoplasm of the gallbladder is an extremely uncommon diagnosis. We present a case of a benign gallbladder paraganglion that was initially incorrectly diagnosed as a neuroendocrine tumour (NET). PRESENTATION OF CASE: A 27-year-old female with symptomatic gallstone disease underwent an uncomplicated laparoscopic cholecystectomy. Routine histopathologic examination suggested the presence of a small adventitial NET. However, histopathological revision was performed by our pathologist because of regional gallbladder carcinoma (GBC) treatment evaluation. The revision demonstrated the presence of a normal paraganglion, a preexistent structure that is only rarely encountered during routine histopathologic examination of the gallbladder. DISCUSSION: Neuroendocrine neoplasms of the gallbladder are extremely rare. Treatment varies from a simple cholecystectomy to extensive surgical resections. Chemotherapy is usually reserved for metastatic disease. In contrast, a gallbladder paraganglion is a benign entity not requiring additional treatment. CONCLUSION: A neuroendocrine neoplasm of the gallbladder may closely resemble a benign paraganglion. If a NET is suspected, the clinician should be aware of the histopathologic mimicry of a paraganglion prior to initiating additional treatments.
ABSTRACT
BACKGROUND: Intramuscular myxoma (IM) is a hypocellular benign soft tissue neoplasm characterized by abundant myxoid stroma and occasional hypercellular areas. These tumors can, especially on biopsy material, be difficult to distinguish from low-grade fibromyxoid sarcoma or low-grade myxofibrosarcoma. GNAS mutations are frequently involved in IM, in contrast to these other malignant tumors. Therefore, sensitive molecular techniques for detection of GNAS aberrations in IM, which frequently yield low amounts of DNA due to poor cellularity, will be beneficial for differential diagnosis. METHODS: In our study, a total of 34 IM samples from 33 patients were analyzed for the presence of GNAS mutations, of which 29 samples were analyzed using a gene-specific TaqMan genotyping assay for the detection of GNAS hotspot mutations c.601C > T and c602G > A in IM, and 32 samples using a novel next generation sequencing (NGS)-based approach employing single-molecule tagged molecular inversion probes (smMIP) to identify mutations in exon 8 and 9 of GNAS. Results between the two assays were compared for their ability to detect GNAS mutations with high confidence. RESULTS: In total, 23 of 34 samples were successfully analyzed with both techniques showing GNAS mutations in 12 out of 23 (52%) samples. The remaining 11 samples were analyzed with either TaqMan assay or smMIP assay only. The TaqMan assay revealed GNAS mutations in 16 out of 29 samples (55%), with six samples c.601C > T (p.R201C; 38%) and ten samples c.602G > A (p.R201H; 62%) missense mutations. The smMIP assay identified mutations in 16 out of 28 samples (57%), with five samples c.601C > T (p.R201C; 31%) and seven samples c.602G > A (p.R201H; 44%) missense mutations. In addition, four samples (25%) revealed novel IM-associated mutations, including c.601C > A (p.R201S), c.602G > T (p.R201L), c.602G > C (p.R201P) and c.680A > G (p.Q227R). Combining the results of both tests, 23 out of 34 sporadic IM samples (68%) showed a GNAS mutation. CONCLUSIONS: Both the TaqMan and the smMIP assay a show a high degree of concordance in detecting GNAS hotspot mutations in IM with comparable sensitivity. However, since the NGS-based smMIP assay permits mutation detection in whole exons of GNAS, a broader range of GNAS mutations can be identified by the smMIP approach.
Subject(s)
Chromogranins/genetics , DNA Mutational Analysis/methods , GTP-Binding Protein alpha Subunits, Gs/genetics , High-Throughput Nucleotide Sequencing/methods , Muscle Neoplasms/genetics , Myxoma/genetics , Adult , Aged , Female , Humans , Male , Middle Aged , MutationABSTRACT
Myoepithelial carcinoma of soft tissue (MEC) and cellular extraskeletal myxoid chondrosarcoma (cEMC) share striking similarities. In this paper, we compare ten MECs with five cEMCs. MEC patients had an equal gender distribution. The age range was 15-76 years (mean, 42 years). Tumours were located on extremities, pelvic girdle, vulva and neck. Follow-up, available for nine patients, ranged from 4 to 85 months (mean, 35 months). Five patients were alive without evidence of disease, two were alive with disease and two died 8 months after the initial diagnosis. cEMCs were from three males and two females with an age range of 37-82 years (mean, 57 years); they presented in extremities, shoulder and paravertebral/cervical. Follow-up, available for four patients, ranged from 6 to 220 months (mean, 61 months). All patients were alive, two with recurrences and/or metastases and two without evidence of disease. Morphologically, the distinction between these two entities was difficult since all cases exhibited features typically seen in myoepithelial tumours. Immunohistochemically, MECs expressed pan-keratin (80 %), epithelial membrane antigen (EMA; 57 %), S100 (50 %), alpha-smooth muscle actin (ASMA; 75 %), calponin (67 %) and p63 (25 %). S100 and EMA were expressed in 40 % of cEMC cases respectively with additional immunoreactivity for p63, ASMA and glial fibrillary acidic protein in one case. Pan-keratin was negative in all neoplasms. NR4A3 rearrangement was present in four of four cEMCs and in none of the MECs. In contrast, three of nine (33 %) MECs and four of five (80 %) cEMCs showed an EWSR1 rearrangement. In summary, MECs and cEMCs share clinical, morphological, immunohistochemical and genetic characteristics. The pathognomic rearrangement of NR4A3 is a useful diagnostic feature in identifying cEMCs.