SciCombinator

Discover the most talked about and latest scientific content & concepts.

Journal: Pathology, research and practice

28

Mesenchymal anal and perianal tumors are relatively uncommon. The majority are malignant. Benign mesenchymal anal tumors are rare. Some are common stromal neoplasms, but with the rare presentation as anal polyps. Other lesions are rare, but unique to the anal/perianal region. Common keratinous cysts might uncommonly present as anal polyps, while other rare cysts are unique to the anogenital region. A retrospective review study of 493 anal and perianal specimens conducted over seven years showed twenty cases (4.0%) of benign anal polypoid lesions. We excluded the usual fibroepithelial polyps, anal tags, papilla, hemorrhoids and warts. We found six cysts, three lipomas, two papillary hidradenomas, two melanocytic nevi, one hamartoma, one xanthogranuloma, one seborrheic keratosis, one hematoma, one fibrous histiocytoma, one granular cell tumor and one lymphangioma. The male to female ratio was 1.5:1. They were found in adults (mean age 37.8years) and in infants (mean age 2.4years). In general, they were smaller than 2cm. They were either asymptomatic or presented with anal pain, bleeding or lumps. Some were clinically confused with the more common non-neoplastic anal tags, hemorrhoids and fibroepithelial polyps/papilla. A variety of common and rare benign lesions might present as anal polyps with important surgical and pathologic challenges and implications.

Concepts: Perianal hematoma, Neoplasm, Seborrheic keratosis, Tumor, Anatomical pathology, Cancer, Oncology, Benign tumor

28

Dermatofibrosarcoma protuberans (DFSP) is a dermal and subcutaneous tumor of intermediate malignancy. The most remarkable cytogenetic feature of DFSP is the chromosomal translocation t(17;22)(q22;q13), causing a fusion of the platelet-derived growth factor beta chain (PDGFB) gene at 22q13, and the collagen type 1 alpha 1 (COL1A1) at 17q22. The aim of the study was to analyze the molecular characteristic of DFSP in conjunction with histopathological and clinical features. We performed fluorescence in situ hybridization (FISH) and multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) to detect chromosomal translocations and fusion gene transcripts in 16 formalin-fixed, paraffin-embedded DFSP samples. In addition, the amplification of PDGFB was also evaluated in the 16 DFSP samples by real-time PCR. FISH analysis revealed that all the 16 samples exhibited COL1A1-PDGFB gene fusion. Eleven out of 11 informative cases (100%) showed fusion transcripts by multiplex RT-PCR analysis. Various exons of the COL1A1 gene were fused with the PDGFB gene. Among them, exon 25 was found to be more frequently involved. Real-time PCR showed that the PDGFB copy number increase in the DFSP samples was higher than in normal skin tissues (p=0.007). Values of FISH fusion signals and PDGFB DNA analysis were variable between samples, but suggested that increased values might be associated with parameters of tumor progression. Our results confirm that analysis of the COL1A1-PDGFB status by FISH and RT-PCR is a useful tool in the confirmation of a DFSP diagnosis. In addition, the analysis of PDGFB copy number status may become a useful diagnostic marker since the gene is a potential target for treatment of DFSP patients.

Concepts: PDGFB, DNA, Genetics, Philadelphia chromosome, Cytogenetics, Molecular biology, Dermatofibrosarcoma protuberans, Chromosomal translocation

27

Hibernomas are uncommon benign lipomatous tumors which show differentiation toward brown fat. To our knowledge, only one case of adrenal hibernoma has been previously reported. We describe a 55-year-old woman showing an incidental, 1.7cm-hibernoma associated with a 2.6cm-cortical adenoma producing primary hyperaldosteronism (Conn’s syndrome), both in the left adrenal gland. The hibernoma was composed predominantly of univacuolated mature fat cells admixed with small vessels. Scattered areas composed of large multivacuolated pale cells with central or paracentral nuclei, mimicking lipoblasts, accounting for less than 30% of the tumor, were found. These cells lacked nuclear hyperchromasia or marked atypia, were S100-positive, and showed numerous mitochondria reactive with the anti-mitochondrial antibody. A diagnosis of lipoma-like hibernoma was made. Pathologists should be aware of this variant of hibernoma to avoid misdiagnosis and excessive treatment.

Concepts: DNA, Primary aldosteronism, Adipose tissue, Oncology, Lipoma, Benign tumor, Hyperaldosteronism, Adrenal gland

27

ErbB receptor tyrosine kinases family plays an important role in cell cycle regulation. Overexpression of ErbB receptors has been described in several solid tumors. The aim of this study was to investigate the levels of ErbB1, ErbB2, ErbB3, and ErbB4 expression in bladder cancer. Urinary bladder tumor samples were obtained from 33 bladder cancers and 7 non-cancerous bladder biopsies. The levels of ErbB1, ErbB2, ErbB3, and ErbB4 genes expression in bladder cancer were determined by real-time PCR. The presence of protein was confirmed by immunostaining. Expression of ErbB1, ErbB2, ErbB3, and ErbB4 genes increased 0.67, 4.72, 2.89, and 2.65-fold, respectively, in bladder tumors as compared with normal tissue. There was a significant difference between immunostaining results of ErbB4 protein in bladder tumors and normal bladder tissue (P<0.01). The present data suggest that ErbB2, ErbB3, and ErbB4 genes may have a role in bladder cancer tumorigenesis.

Concepts: ErbB, Urinary bladder, Receptor tyrosine kinase, Tyrosine kinase, Bladder cancer, Gene expression, Signal transduction, Cancer

26

The aim of this study was to compare the expressions of fascin and EMMPRIN in primary malignant, borderline and benign mucinous ovarian tumors, and to investigate the relationship of these markers with tumor progression and their applicability to differential diagnosis.

Concepts: Medical diagnosis, Oncology, Benign tumor, Medical terms, Ovarian cancer, Differential diagnosis, Cancer

26

Endometriosis is associated with an increased risk of ovarian cancer. Few studies have also shown increased risk of breast cancer. BRCA1/2 mutations are linked to an increased risk of breast and ovarian cancers but their relation to endometriosis is unknown. The objective of this study was to examine the mutation rate of BRCA1/2 among women with surgically treated ovarian endometriosis. We collected 126 specimens from Jewish Ashkenazi women with endometriotic (76) and control non-endometriotic (50) ovarian cysts, reviewed the pathological diagnoses and extracted DNA from all samples. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), samples were examined for the founder germline mutations of BRCA1/2, most common among Ashkenazi Jews. The rate of mutations in each group was calculated and compared. BRCA1/2 mutation rate was 1/76 (1.3%) in the endometriotic cyst study group and 1/50 (2%) in the control non-endometriotic cysts, showing no statistically significant difference between the groups (p=0.84). BRCA1/2 mutation rate was similar to the previously reported rate among Jewish Ashkenazi women. BRCA1/2 mutation rates in patients with endometriotic ovarian cysts and with non-endometriotic ovarian cysts are similar. A larger cohort is required to completely exclude the possibility of an association between BRCA1/2 mutations and surgically treated endometriosis.

Concepts: Endometriosis, Mass spectrometry, Mutation, BRCA1, BRCA2, Ovarian cyst, Ovarian cancer, Cancer

24

Primary mucinous adenocarcinoma of the renal pelvis is easily misdiagnosed and it was rarely reported in the literature. We describe in this study a case of 40-year-old male patient presented with right lumbar pain of one year duration and elevated level of carcinoembryonic antigen (CEA). After a series of imaging examinations, the initial impression was a cystic renal cell carcinoma. Right radical nephrectomy was performed on the patient. The postoperative pathological examination indicated a primary mucinous adenocarcinoma of enteric type of the renal pelvis. After surgical removal of the tumor, an immunotherapy was administrated to prevent recurrence. The patient survives upon this report. A review of pertinent literature is also presented.

Concepts: Carcinoembryonic antigen, Hospital, Examination, Anatomical pathology, Cancer, Nephrectomy, Kidney, Renal cell carcinoma

23

Selective progesterone receptor modulators have shown efficacy in the treatment of endometriosis, however they are not currently licensed in Canada for this purpose. Their histomorphological effects have been well documented in the endometrium, but not in endometriosis.

Concepts: Menstrual cycle, Endometrium, Progesterone receptor, Endometriosis, Progesterone, Selective progesterone receptor modulator

1

The aim of the study was detailed clinicopathological investigation of SMARCB1/INI1-deficient sinonasal carcinomas, including molecular genetic analysis of mutational status and DNA methylation of selected protooncogenes and tumor suppressor genes by means of next generation sequencing (NGS) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). A total of 4/56 (7%) cases of SMARCB1/INI1-deficient carcinomas were detected among 56 sinonasal carcinomas diagnosed over a 19year period using immunohistochemical screening. The series comprised 3 males and 1 female, aged 27-76 years (median 64 years). All tumors arose in the nasal cavity. Three neoplasms were diagnosed in advanced stage pT4. During the follow-up period (range 14-111 months (median 72 months)), three tumors recurred locally, but none of the patients developed regional or distant metastases. Ultimately, two patients died due to the tumor. Microscopically, all tumors consisted of infiltrating nests of polygonal basaloid cells with a variable component of rhabdoid cells with eosinophilic cytoplasm. Immunohistochemically, there was almost diffuse expression of cytokeratins (CK), p16, p40 and p63 in all cases, while expression of CK5/6, CK7 and vimentin was only focal or absent. The detection of NUT gave negative results. In three cases, the absence of SMARCB1/INI1 expression was due to deletion of SMARCB1/INI1 gene. Methylation of SMARCB1/INI1 gene was not found. One tumor harbored HPV18 E6/E7 mRNA. All 12 genes (BRAF, BRCA1, BRCA2, KIT, EGFR, KRAS, NRAS, PDGFRA, PIK3CA, PTEN, RET, and ROS1) tested for mutations using NGS were wild-type. Regarding DNA methylation, all four SMARCB1/INI1-deficient tumors showed methylation of RASSF1 gene by means of MS-MLPA. There was a statistically significant difference in RASSF1 gene methylation between SMARCB1/INI1-deficient and SMARCB1/INI1-positive tumors (p=0.0095). All other examined genes (ATM, BRCA1, BRCA2, CADM1, CASP8, CD44, CDKN1B, CDKN2A, CDKN2B, CHFR, DAPK1, ESR1, FHIT, GSTP1, HIC1, KLLN, MLH1a, MLH1b, RARB, and VLH) were unmethylated. In summary, we described four cases of SMARCB1/INI1-deficient sinonasal carcinoma with detailed clinicopathological data indicating that these tumors can be regarded as a distinct entity with aggressive behaviour. For the first time, we performed analysis of DNA methylation in SMARCB1/INI1-deficient sinonasal carcinomas, reporting on significantly higher methylation of RASSF1 gene in this neoplasm.

Concepts: Anatomical pathology, DNA methylation, DNA repair, Gene expression, Gene, Genetics, DNA, Cancer

1

Mucosal biopsies from the head and neck are often small and poorly oriented, which impedes diagnostic interpretation, especially in patients with a history of cancer, being monitored for recurrence. A cocktail of antibodies targeted against DNA topoisomerase IIA and mini-chromosome maintenance protein 2 (MCM2/TOP2A, ProExC), markers of aberrant S-phase induction, have been used with success as a diagnostic adjunct in the evaluation of squamous dysplasia of the uterine cervix. We tested the utility in head and neck biopsies to see if ProExC could be used to discriminate reactive/inflammatory from true pre-neoplasia. Sixty-four archival biopsies were selected from patients who presented to the surgeon with an indication for biopsy to “rule out” dysplasia. Histologically, all biopsies showed nonspecific atypia that was difficult to discriminate from dysplasia. Twenty-three of the patients progressed to squamous carcinoma and the rest remained benign over five years follow-up. Cases stained with ProExC by IHC methods showed a significant pattern of expression (p=0.026). The staining was greatest in patients without a history of prior head and neck cancer but was not significant. Our results show that ProExC, used in conjunction with the H&E slide, can enhance the predictive power of a mucosal biopsy in a cohort of patients.

Concepts: Skin biopsy, Uterus, Cervix, Head and neck cancer, DNA, Squamous cell carcinoma, Vagina, Cancer