Adenomatous Component Research Articles

Colorectal advanced neoplasms occur through dual carcinogenesis pathways in individuals with coexisting serrated polyps.

BackgroundIndividuals with serrated polyps (SP) are at higher risk for synchronous colorectal advanced neoplasms (AN) and cancers. However, it remains unclear whether there is a unique involvement of the serrated pathway and/or the classical adenoma-carcinoma sequence in this setting.MethodsColorectal ANs, which include tubular adenomas ≥10 mm, adenomas with villous histology, high-grade intraepithelial neoplasms, and cancers, were collected retrospectively. The groups included ANs with (AN+SP) or without (AN-only) coexisting SPs. Clinicopathological findings were compared between groups. BRAF and KRAS mutations in ANs and SPs, and methylation levels at long interspersed element-1 (LINE-1) in adjacent mucosa were determined by pyrosequencing.ResultsSeventy-five ANs from 40 patients in the AN+SP group, and 179 ANs from 119 patients in the AN-only group were analyzed. There were no significant differences in clinicopathological findings between the two groups, except that intraepithelial neoplasia in the AN+SP group was more likely to be located in the right colon (P = 0.018). BRAF mutations were significantly more frequent in the AN+SP group (P = 0.003), while KRAS mutations showed no significant differences between groups (P = 0.142). The majority of high-grade intraepithelial neoplasms in both groups showed a contiguous component of conventional adenoma. Individuals with large and right-sided SPs had significantly more conventional adenomas compared to those without such SPs (P = 0.027 and P = 0.031, respectively). Adjacent mucosa from individuals with multiple and large SPs showed significantly lower methylation levels at LINE-1 compared to individuals without such associated SPs (P = 0.049 and P = 0.015, respectively).ConclusionOur data suggest that both the adenoma-carcinoma sequence and the serrated pathway are operational in individuals with coexisting ANs and SPs. The reduced methylation levels at LINE-1 in the background mucosa suggest the possibility of an underlying ‘field defect’.

Sorbitol Dehydrogenase Overexpression and Other Aspects of Dysregulated Protein Expression in Human Precancerous Colorectal Neoplasms: A Quantitative Proteomics Study

Colorectal adenomas are cancer precursor lesions of the large bowel. A multitude of genomic and epigenomic changes have been documented in these preinvasive lesions, but their impact on the protein effectors of biological function has not been comprehensively explored. Using shotgun quantitative MS, we exhaustively investigated the proteome of 30 colorectal adenomas and paired samples of normal mucosa. Total protein extracts were prepared from these tissues (prospectively collected during colonoscopy) and from normal (HCEC) and cancerous (SW480, SW620, Caco2, HT29, CX1) colon epithelial cell lines. Peptides were labeled with isobaric tags (iTRAQ 8-plex), separated via OFFGEL electrophoresis, and analyzed by means of LC-MS/MS. Nonredundant protein families (4325 in tissues, 2017 in cell lines) were identified and quantified. Principal component analysis of the results clearly distinguished adenomas from normal mucosal samples and cancer cell lines from HCEC cells. Two hundred and twelve proteins displayed significant adenoma-related expression changes (q-value < 0.02, mean fold change versus normal mucosa ±1.4), which correlated (r = 0.74) with similar changes previously identified by our group at the transcriptome level. Fifty-one (∼25%) proteins displayed directionally similar expression changes in colorectal cancer cells (versus HCEC cells) and were therefore attributed to the epithelial component of adenomas. Although benign, adenomas already exhibited cancer-associated proteomic changes: 69 (91%) of the 76 protein up-regulations identified in these lesions have already been reported in cancers. One of the most striking changes involved sorbitol dehydrogenase, a key enzyme in the polyol pathway. Validation studies revealed dramatically increased sorbitol dehydrogenase concentrations and activity in adenomas and cancer cell lines, along with important changes in the expression of other enzymes in the same (AKR1B1) and related (KHK) pathways. Dysregulated polyol metabolism might represent a novel facet of metabolome remodeling associated with tumorigenesis.

Quantitative shotgun proteomics reveals early markers of colorectal carcinogenesis (591.1)

Colorectal adenomas are cancer precursor lesions of the large bowel. Using iTRAQ 8‐plex labelling, OFFGEL electrophoresis, and LC‐coupled tandem MS, we investigated the proteome of 30 colorectal adenomas and paired normal mucosal samples (prospectively collected during colonoscopy), and that of normal (HCEC) and cancerous (SW480, SW620, CACO2, HT29, CX1) colon epithelial cell lines. A total of 4325 and 2017 non‐redundant protein families were identified and quantified in tissue and cell lines, respectively. Principal component analysis clearly distinguished adenomas from normal mucosa, and cancer cell lines from HCEC cells. Two hundred twelve proteins displayed significant adenoma‐related expression changes (q‐value&lt;0.02, mean fold change +/‐1.4), which correlated (r=0.74) with similar changes previously identified by our group at the transcriptome level. Fifty one proteins displayed directionally similar expression changes in colorectal cancer cells (vs HCEC cells) and were therefore attributed to the epithelial component of adenomas. Although benign, adenomas already exhibited protein expression changes previously documented only in advanced colorectal cancers. They also disclosed several novel changes with potentially important roles in early‐stage large bowel tumorigenesis, including the marked upregulation of a key enzyme in the polyol pathway.Grant Funding Source: Supported by the Swiss National Science Foundation

Relative Proportions of Stromal to Cellular Components of Pleomorphic Adenomas

The purpose of this study was to evaluate whether the relative proportions of stromal to cellular components of pleomorphic adenomas have an effect on the shear elastic modulus determined by shear wave elastography (SWE). This study was approved by the Ethics Committee of our institution and performed between September 2011 and December 2012. Thirty-five patients who underwent surgery for a parotid mass were included in the study. The maximum shear elastic modulus of the mass was measured by SWE. Pleomorphic adenomas were histopathologically subdivided into stroma-poor, intermediate-stroma, and stroma-rich tumors based on the relative proportion of stromal to cellular components. The maximum shear elastic modulus values of the pleomorphic adenomas ranged from 12.6 to 291.9 kPa (mean ± SD, 120.9 ± 92.8 kPa). The Friedman test revealed a statistically significant relationship between the stromal amount and maximum shear elastic modulus (P < .001). Stroma-poor adenomas (mean, 32.3 ± 27.7 kPa; range, 12.6-81.1 kPa) were softer on SWE than stroma-rich adenomas (mean, 174.1 ± 48.4 kPa; range, 92.7-217.2 kPa; P = .009). No such significant difference was detected between stroma-poor and intermediate-stroma tumors (mean, 146.3 ± 106.1 kPa; range, 19.1-291.9 kPa; P = .062) or between intermediate-stroma and stroma-rich tumors (P = .465). Shear wave elastography depicts pleomorphic adenomas with a variable appearance, which is due to the relative proportions of stromal to cellular contents in the tumors.

Carcinoma Ex-Pleomorphic adenoma metastasising to vertebra diagnosed on frozen section - A case report

Carcinoma ex-Pleomorphic adenoma is defined as a carcinoma that arises in the epithelial and/or myoepithelial component of a pleomorphic adenoma. Prognosis and management is highly dependent on the type of carcinoma and extent of invasion. The malignant component is classified as non-invasive (intracapsular), minimally invasive, and widely invasive. Non-invasive and minimally invasive tumours have an excellent prognosis and very low metastatic potential. This case study is of a 59-year-old man with a tumour in the Thoracic 9 vertebra that was compressing the spinal cord. Multiple tissue fragments were sent to our department for frozen tissue assessment which microscopically showed a tumour with features resembling carcinoma ex-pleomorphic carcinoma with a malignant component suggestive of myoepithelial carcinoma. This was confirmed with immunohistochemistry done on further samples of the tumour. The patient was discovered in our databases to have had a previous left parotidectomy in 2008 for a carcinoma ex pleomorphic adenoma with features similar to the frozen section tissue. The clinicians involved with this case had no knowledge of this. This case, whilst rare, highlights the importance of the pathologist's role in diagnosis and patient management.

Colonic Adenocarcinoma of a Neovagina in a Patient with Mullerian Agenesis

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, also known as Mullerian agenesis, is a largely sporadic disorder resulting in absence or hypoplasia of the vagina, uterus, and fallopian tubes. In order to foster adequate psychosocial development and sexual intercourse, a number of surgical procedures are available, one of which is the creation of a neovagina from a segment of sigmoid colon. In this report, we describe a patient who presented at age 17 amenorrhea and was found to have MRKH. She underwent vaginal reconstruction with a neovagina from a segment of her sigmoid colon at age 19. Subsequent to this procedure, the patient developed carcinoma of the breast and renal cell carcinoma, and in addition developed an invasive mucinous adenocarcinoma of her neovagina. This is only the third case of an adenocarcinoma arising in a neovagina in the setting of MRKH, and the first case described with an accompanying adenomatous component. All three cases to date demonstrated a mucinous phenotype. Overall, this case emphasizes that neovaginal mucosa may undergo neoplastic transformation, and that recognition of this possibility is important in long-term follow up care for patients affected MRKH treated by surgical reconstruction.

Abstract P5-13-09: Evaluation on the risk factors and prognosis for patients with synchronous bilateral breast cancer in a Chinese cohort

Abstract Background: There has been an increasing rate of synchronous bilateral breast cancers, mainly because of the increased morbidity, improved detection abilities, better prognosis and higher life expectancy of breast cancer patients. However, evidences in the literature regarding the risk factors of bilateral breast cancers are scare, and the survival of synchronous bilateral breast cancers still remain controversies. The purpose of the present study is to investigate the risk factors and prognosis of bilateral breast cancers in a Chinese cohort. Methods: The present study included 181 patients with synchronous bilateral breast cancer and 10,831 patients with unilateral breast cancer treated in Fudan University Shanghai Cancer Center between Jan 2007 and Dec 2012. Patients with metastases or inflammatory diseases, or metachronous bilateral breast cancer (after 6 months of first cancer) were excluded. Age of the cases, family history, menopausal status, histology types, pathological stages, types of accompanied benign lesions, and patterns of surgeries and adjuvant therapies were examined to investigate the risk factors of bilateral breast cancers. Results: Patients with synchronous bilateral breast cancer were significantly elder than those with unilateral breast cancer (mean age 53 yrs vs. 51yrs, p&amp;lt;0.001). Presence of sclerosing adenoma and lobular carcinoma component were the two independent risk factors of early-stage synchronous bilateral breast cancer, with the relative risk rate at 5.52 (95% CI: 3.04-10.01) and 5.00 (95% CI: 2.64-9,47), respectively. The rate of in situ carcinoma with or without microinvasion was significantly higher in patients with sclerosing adenoma associated synchronous bilateral breast cancers at 64.3%. With a median follow-up of 35 months, the disease free survival for synchronous bilateral breast cancer was 95.0%, similar to that of unilateral breast cancer. However, for synchronous bilateral breast cancer patients with N3 disease or previously received neoadjuvant therapy (20 cases), the 1.5 year-disease free survival was merely 50%, significantly worse than that of unilateral breast cancer with N3 disease or previous neoadjuvant therapy. Conclusion: The rate of synchronous bilateral breast cancer was higher in patients with sclerosing adenosis or lobular carcinoma component. The prognosis for early-stage synchronous bilateral breast cancer was similar to those with early-stage unilateral breast cancer. However, among patients with N3 disease or previously received neoadjuvant therapy, synchronous bilateral cohort was associated to worse survival compared with unilateral cohort. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-13-09.

A Very Unusual Cause of Diarrhea in a 60-Year-Old Man

Purpose: A 60-year-old man presented with a nine-month history of diarrhea associated with 40-lb weight loss. He also complained of gradual loss of his nails and hair, burning of the tongue, decreased taste sensation and hyperpigmentation of his skin. He had a screening colonoscopy at the age of 50, which was normal. His laboratory tests were significant for low albumin and hemoglobin. Stool studies were all negative. A CT abdomen showed abnormal thickening of the distal gastric body and antrum. An upper endoscopy revealed diffuse mucosal abnormality characterized by erythema and nodularity in the gastric body and antrum, as well as in the duodenum. A colonoscopy revealed many small-to-medium sized polyps throughout the colon, along with patchy areas of moderately congested and nodular mucosa in the colon and the terminal ileum. Gastric biopsies revealed edema and foveolar hyperplasia suggestive of hyperplastic polyps, but no dysplasia. Random colonic biopsies revealed active focal colitis with multiple fragments of inflammatory polyps. The patient was diagnosed with Cronkhite-Canada syndrome (CCS). He was treated with prednisone and azathioprine with subsequent improvement in symptoms. CCS is an extremely rare non-hereditary disorder characterized by diffuse gastrointestinal polyps, diarrhea, weight loss, onychodystrophy, alopecia, hypoguesia and skin hyperpigmentation. Ever since being first described in 1955, a little over 400 cases have been reported worldwide with the majority of patients being from Japan. The GI tract polyps are of the hamartomas non-neoplastic type. Dysplastic changes can develop in these polyps, and the lifetime colorectal cancer risk is about 25%. Mortality rate, mostly related to the protein-losing enteropathy approaches 50% at 5 years from the time of diagnosis. No specifi c treatment has been standardized, but corticosteroids and azathioprine have been used with good results. Successfully treated patients should clear most of the inflammatory polyps, and any remaining polyps should be resected, as they are more likely to have an adenomatous component. Any dysplastic changes detected may warrant intestinal resection.Figure: Colon polyps.

Invasive adenocarcinoma arising from a mixed hyperplastic/adenomatous polyp and synchronous transverse colon cancer

An admixture of hyperplastic and adenomatous components within the same polyp is unusual. Adenocarcinoma arising from a mixed hyperplastic/adenomatous polyp (MHAP) occurs even more rarely. We report the first case of a 59-year-old male who presented with invasive adenocarcinoma originating from a MHAP at a sigmoid colon and synchronous transverse colon cancer.

Magnetic Resonance Imaging Criteria to Predict Complete Excision of Parasellar Pituitary Macroadenoma on Postoperative Imaging

Purpose To evaluate preoperative magnetic resonance imaging (MRI) criteria for their ability to predict the complete removal of parasellar pituitary macroadenoma on the 3-month postoperative MRI. Methods Dedicated pre- and postoperative pituitary MRI studies were reviewed in 49 patients who had undergone transsphenoidal surgery for macroadenomas with potential unilateral parasellar involvement. Twelve preoperative MRI findings and postoperative MRI outcomes were statistically compared. Results Depiction of the inferolateral (positive predictive value [PPV]: 0.6; negative predictive value [NPV], 0.92) and lateral (PPV: 0.65; NPV: 0.85) compartments of the cavernous sinus and the percentage of intracavernous carotid artery encasement (PPV: 0.63; NPV, 1.0 for <50% encasement) were the only criteria significantly predictive of parasellar tumor complete resection. The odds ratios indicated that depiction of the lateral venous or inferolateral venous compartments increased the likelihood of a complete resection by 6 times, whereas for every 25% reduction in intracavernous carotid artery encasement, the chance of a complete resection increased 3.4 times. Conclusion The preoperative MR imaging features that are useful in predicting the complete removal of the parasellar component of a pituitary adenoma as assessed by postoperative MRI are (1) depiction of the lateral and inferolateral compartment of the cavernous sinus and (2) decreasing encasement of the intracavernous carotid artery.

Identification of APC Gene Mutations in Jejunal Carcinomas from a Patient with Familial Adenomatous Polyposis

Jejunal carcinoma in patients with familial adenomatous polyposis has been rarely reported, and little is known about its association with genetic alterations of the APC gene. A 52-year-old woman with familial adenomatous polyposis underwent palliative resection of the proximal jejunum because of two circumferential tumors associated with peritoneal carcinomatosis. A histological examination revealed that one tumor was a poorly differentiated adenocarcinoma, and that the other was a moderately differentiated adenocarcinoma with adenomatous components. The patient did not respond to standard chemotherapy and died of disseminated disease 8 months after surgery. A genetic analysis of the APC gene identified somatic mutations in each tumor (c.4450delAG and p.R1450X) in addition to the germline mutation (c.3984del5), all of which form stop codons, resulting in truncated APC products. This report is the first description of how a second hit to the APC gene can be involved in carcinogenesis of the jejunum in familial adenomatous polyposis.

SOX10 is a novel marker of acinus and intercalated duct differentiation in salivary gland tumors: a clue to the histogenesis for tumor diagnosis

Salivary gland tumors are relatively rare and morphologically diverse and heterogeneous tumors; therefore, histogenesis-based tumor markers are sorely needed to aid in diagnosing and determining the cell type of origin. SRY-related HMG-box 10 (SOX10) protein is a transcription factor known to be crucial in the specification of the neural crest and maintenance of Schwann cells and melanocytes. In addition, positive expression has also been implicated in the major salivary gland. Here, we examined SOX10 expression in various salivary gland tumors to correlate this expression with myoepithelial markers. Overall, 76 malignant and 14 benign tumors were examined. SOX10 expression clearly delineated two distinct subtypes of human salivary gland tumors; acinic cell carcinomas, adenoid cystic carcinomas, epithelial-myoepithelial carcinomas, myoepithelial carcinomas, and pleomorphic adenomas, including the pleomorphic adenoma component of carcinoma, were SOX10 positive, while salivary duct carcinomas, mucoepidermoid carcinomas, an oncocytic carcinoma, Oncocytomas, and Warthin tumors were SOX10 negative. Also, SOX10 was expressed in solid-type or non-specific morphology salivary gland tumors, but was not expressed in poorly differentiated squamous cell carcinomas. In normal human salivary gland tissue, SOX10 expression was specific to the nuclei of acini and both luminal and abluminal cells of intercalated ducts but not in other sites. Moreover, the murine model suggested that SOX10 continued to be expressed from the developmental stage to adulthood in the acinar and both luminal and abluminal intercalated ducts in the major salivary gland. Thus, SOX10 is a novel marker for diagnosing and understanding the histogenesis of salivary gland tumors.

Mo1394 Towards the Detection of Bile Acid Diarrhea: A Novel Non-Invasive Approach Using Electronic Noses (E-Nose) and Field Asymmetric Ion Mobility Spectroscopy (FAIMS)

OBJECTIVES: Colorectal cancer develops through multiple pathways including the adenomacarcinoma sequence and the serrated pathway. Individuals with serrated polyps (SP) are at higher risk of developing synchronous advanced colorectal neoplasia (AN) and cancer, but the molecular pathways underlying this malignancy remain poorly understood in these individuals. In this study, we characterized patients with coexisting colorectal AN and SP by examining the methylation levels of long interspersed nucleotide element-1 (LINE-1) in the adjacent normal mucosal tissues. METHODS: Colorectal ANs were retrospectively collected. The case group included ANs with coexisting SPs, and the control group consisted of ANs without coexisting SPs. Clinicopathological findings were compared between groups. BRAF and KRAS mutations in the ANs and SPs and LINE-1 methylation levels in adjacent mucosa were examined by quantitative bisulfite pyrosequencing. RESULTS: Seventy-five ANs from 40 patients in the case group, and 179 ANs from 119 patients in the control group were collected and analyzed. There were no significant differences in clinicopathological findings between the 2 groups of ANs, except that intraepithelial neoplasia in the case group was more frequently located in the right colon. BRAF mutations were significantly more frequent in the case group, while KRAS mutation showed no significant differences between groups. Most patients with high-grade intraepithelial neoplasia in both groups showed a component of conventional adenoma, while only one patient with high-grade intraepithelial neoplasia in the control group had a component of SP. Individuals with

Carcinoma Expleomorphic Adenoma of the Submandibular Gland

ABSTRACT Background and objectives Carcinoma expleomorphic adenoma (CXPA) is a rare neoplasm of the salivary gland which arises in the epithelial component of a pleomorphic adenoma. It is not automatically a high-grade tumor as is traditionally suggested and should be further qualified as to type, grade of carcinoma and extent, since intracapsular and minimally invasive tumors behave favorably. Setting Department of Head and Neck oncosurgery, Kidwai Memorial Institute of Oncology, Bengaluru. Case Report A 38-year-old female was referred to our outpatient clinic with history of a painless swelling in the left side of the neck since 8 years. Fine needle aspiration revealed carcinoma of the submandibular gland. Contrast enhanced CT revealed a large heterogeneously enhancing mass lesion in the submandibular fossa with the gland not seen separately. Lymph nodes in level Ib and II were enlarged. Excision of the tumor revealed CXPA with foci of high grade mucoepidermoid carcinoma. Conclusion CXPA should no longer be considered a specific diagnosis but a category in which the carcinoma should be typed, graded and quantitated to impart more prognostically and therapeutically relevant data for efficient management. How to cite this article Naik SM, Shenoy AM, Chavan P, Halkud R, Biswas S, Kalloli M, Gupta S, kudpaje A. Carcinoma Expleomorphic Adenoma of the Submandibular Gland. J Postgrad Med Edu Res 2013;47(3):162-166.

1114 Status of mismatch repair genes hMSH2 and hMSH6 in colorectal cancer in Saudi patients: an immunohistochemical analysis

This study aimed to identify the status of 2 major microsatellite instability markers (repair genes hMSH2 and hMSH6) in colorectal cancer cases operated at King Khalid University Hospital, Riyadh, Saudi Arabia between 2007 and 2009. Immunohistochemical study of microsatellite instability was done with antibodies to hMSH2 and hMSH6. A total of 32 blocks were analysed from patients aged 16-83 years (median 56 years); 14 blocks (43.8%) were from resections and 18 (56.2%) were from biopsies. An adenomatous component was present in 4 (12.5%) blocks. The colonic carcinoma, the adenomas and the normal tissue showed strong nuclear reactivity to hMSH2 and hMSH6 in 96.9% of the cases. The rate of loss of expression was 3.1%. The rate of mutation in our sampled population was low and matched the rate reported in the literature from industrialized countries. Further studies are needed to confirm the use of these markers in the diagnosis of colorectal cancer.

Early colorectal carcinomas: CD10 expression, mucin phenotype and submucosal invasion

We analyzed 170 tumors (polypoid, 98; non-polypoid, 72) of early colorectal carcinoma with or without submucosal invasions (Tis and T1 of TNM classification) from 161 patients to evaluate correlations between clinicopathological factors and immunohistochemical expressions of CD10, MUC2, and MUC5AC. The coexistence of adenomatous components was significantly less common in non-polypoid carcinomas (4.2%) than in polypoid carcinomas (66.3%) (P < 0.0001). Non-polypoid carcinomas were smaller in size and tended to infiltrate into the submucosa with higher incidence of lymphatic and venous permeations. CD10 was more frequently expressed in non-polypoid carcinomas (70.8%) than in polypoid carcinomas (51.0%) (P= 0.01). Total carcinomas with high grade atypia showed higher incidence of CD10 expression (60.6%) than those with low grade atypia (28.9%) (P < 0.0001). Carcinomas with low grade atypia exhibited a higher incidence of MUC2 and MUC5AC expression (91.1% and 57.8%, respectively), when compared with carcinomas with high grade atypia (41.6% and 20.0%, respectively) (both, P < 0.0001). In submucosal invasive carcinomas with residual intramucosal carcinoma component (IMCC), CD10 expression in IMCC and submucosal invasive carcinoma component (SMCC) simultaneously exhibited identical positive or negative results, regardless of the polypoid or non-polypoid growth pattern. The CD10 expression may occur in the early stage of carcinogenesis within the mucosa, and these neoplasms may retain CD10 in SMCC, possibly resulting in more advanced stages of stromal invasion and distant metastases. In conclusion, our data suggest that the CD10 expression and mucin phenotypes may be potentially useful markers for estimating biological properties of early colorectal carcinomas.

Neuroendocrine tumor in gastric adenoma: a diagnostic pitfall mimicking invasive adenocarcinoma

Neuroendocrine tumor (NET) in adenoma of the gastrointestinal tract is a rare mixed glandular-endocrine neoplasm and has uncommonly been described mostly in the colon. Histologically, this tumor is composed of a predominant proportion of benign adenomatous component and a small portion of well-differentiated NE component. Only three cases of NET in gastric adenoma have been reported in the literature. We present 4 cases of NET in gastric adenoma mimicking invasive adenocarcinoma. The NETs were 0.62 mm to 4.1 mm in size and located at the basal lamina propria, muscularis mucosa and submucosa. Histologically, NETs consisted of nests, cords, tubules, and clusters of cells that predominantly interposed between the foveolar base without disturbing the overall polyp architecture. The lesions were completely removed by endoscopic submucosal dissection in three cases and in one case, subtotal gastrectomy was performed because endoscopic biopsy was invasive adenocarcinoma. The patients’ clinical course was uneventful without an evidence of recurrence or metastasis. The recognition of NET in gastric adenoma will help avoid potential diagnostic pitfalls masquerading as invasvie adenocarcinomas posed by their infiltrative pattern into submucosa.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1688552293761001

Myoepithelial carcinoma ex pleomorphic adenoma: a rare intraosseous entity

After reading the article by Damin Zhao et al. on primary central carcinoma ex pleomorphic adenoma (CXPA), which was quite interesting and informative, I think there are some controversies and ambiguities that need to be discussed. 1The author titled the paper as concerning primary central CXPA.1Zhao D. He H. Fang M. Liu M. Ji B. He Z. Primary central carcinoma ex pleomorphic adenoma of the mandible: report of a rare case and literature review.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011; 112: e24-e28Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar I think that the word “primary” is inappropriate here, because the primary tumor that arose at the site was a benign pleomorphic adenoma. The carcinoma had not developed de novo. The authors stated that 80% of the histologic picture was that of myoepithelial carcinoma and that a benign component of pleomorphic adenoma was also seen. Therefore I humbly suggest that the case should be listed as myoepithelial CXPA of the mandible and that the word “primary” should be dropped. One case that shares similar behavior has been reported in an infant.2Asai S. Tang X. Ohta Y. Tsutsumi Y. Myoepithelial carcinoma in pleomorphic adenoma of salivary gland type, occurring in the mandible of an infant.Pathol Int. 1995; 45: 677-683Crossref PubMed Scopus (16) Google Scholar It could be hypothesized that the heterotropic salivary tissue entrapped in the mandible gave rise to a pleomorphic adenoma first, which then transformed into a myoepithelial carcinoma. Demonstration of a residual focus of pleomorphic adenoma, as in this case, can be considered as histologic evidence that the lesion arose from an intraosseous pleomorphic adenoma.3McCluggage W.G. Primrose W.J. Toner P.G. Myoepithelial carcinoma (malignant myoepithelioma) of the parotid gland arising in a pleomorphic adenoma.J Clin Pathol. 1998; 51: 552-556Crossref PubMed Scopus (29) Google Scholar2Two masses were mentioned. The sentence, “during surgery, another mass was found connected to the mandibular mass,” does not specify if both were intraosseous or if there was a cortical perforation between 2 separate lesions. If both of the tumors were not related to each other, it could be interpreted as separate benign and a malignant entities occurring synchronously.4Curry J.L. Petruzzelli G.J. McClatchey K.D. Lingen M.W. Synchronous benign and malignant salivary gland tumors in ipsilateral glands: a report of two cases and a review of literature.Head Neck. 2002; 24: 301-306Crossref PubMed Scopus (42) Google Scholar If there was perforation of the cortical plate, it may represent invasion of soft tissue salivary gland neoplasms into the mandible.5Johnston N.J. Lutterloch M.J. Lutterloch M.J. Cystadenocarcinoma of salivary gland presenting as a cystic lesion in the mandible.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006; 101: 201-204Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar3It is interesting to note that despite the aggressive behavior of the lesion, there was no lymph node involvement noticed clinically, whereas the frozen-section evaluation of nodes revealed malignant epithelial tumor.4There is no mention of the use of immunohistochemical markers that could be used to identify myoepithelial cells, e.g., smooth muscle protein markers such as alpha-SMA, SMMHC, h-caldesmon, basic calponin, keratins 14, 15, and 17, alpha1-beta1-integrin, and vimentin.6Ogawa Y. Immunocytochemistry of myoepithelial cells in the salivary glands.Prog Histochem Cytochem. 2003; 38: 343-426Crossref PubMed Scopus (88) Google Scholar Primary central carcinoma ex pleomorphic adenoma of the mandible: report of a rare case and literature reviewOral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and EndodonticsVol. 112Issue 2PreviewWe report a rare case of primary carcinoma ex pleomorphic adenoma (CXPA) of the mandible. A 13-year-old girl presented with a large mass, measuring about 30 cm in its greatest dimension, involving the mandible. She was referred to our department for surgery, and her postoperative course was uneventful; she is currently free from the disease 48 months after surgery. Primary CXPAs located centrally within the jawbones are rare with only 10 cases reported in the English and Chinese literature. This case illustrates 2 key facts regarding the diagnosis and therapy of CXPA. Full-Text PDF

Medical Management for BPH-Present Concept

Purpose of review: Benign prostatic hyperplasia(BPH) is one of the most common disease to affect men beyond middle age to cause lower urinary tract symptoms(LUTS). Medical therapy is now well established as the first option in the management of symptomatic BPH. Selective α1a blockers which relaxes the smooth muscle component of prostatic urethra and bladder neck and the 5αreductase enzyme inhibitors (5ARI) which inhibit or regresses the growth of adenomatous component of prostatic gland have proved quite efficacious when given as a monotherapy or in combination. Lately anticholinergic drugs like tolterodine or solifenacetin are given in combination with α blockers where irritative bladder symptoms like- urgency, frequency or urge incontinence predominates .Though these two drugs are physiologically antagonistic , each exerts its beneficial effect acting at different target sites eg.,- overactive detrusor muscle and spasmodic bladder neck sphincter area. More recently 5 phosphodieasterase inhibitors like Sildenefil citrate(Viagra) or the long acting variant Tadafil citrate(Tazzle) are prescribed in combination with α blockers to enhance the effect of smooth muscle relaxation at the bladder neck and also to take care of the erectile dysfunction(frequently experienced by many ageing men with BPH) Various phytotherapeutic products and food supplements used by traditional medical therapists failed to give a consistent favourable result. The present review gives a bird s eye view on recent advances in the medical management of BPH. Key Words: Benign prostatic hyperplasia, Medical therapy, 5α reductase inhibitors, Selective α blockers, Phosphodiesterase inhibitors

A new whole genome amplification method for studying clonal evolution patterns in malignant colorectal polyps

To identify the genetic drivers of colorectal tumorigenesis, we applied array comparative genomic hybridization (aCGH) to 13 formalin-fixed paraffin-embedded (FFPE) samples of early, localized human colon adenocarcinomas arising in high-grade adenomas (so-called "malignant polyps"). These lesions are small and hence the amount of DNA is limited. Additionally, the quality of DNA is compromised due to the fragmentation as a consequence of formalin fixation. To overcome these problems, we optimized a newly developed isothermal whole genome amplification system (NuGEN Ovation® WGA FFPE System). Starting with 100 ng of FFPE DNA, the amplification system produced 4.01 ± 0.29 μg (mean ± standard deviation) of DNA. The excellent quality of amplified DNA was further indicated by a high signal-to-noise ratio and a low derivative log(2) ratio spread. Both, the amount of amplified DNA and aCGH performance were independent of the age of the FFPE blocks and the associated degradation of the extracted DNA. We observed losses of chromosome arms 5q and 18q in the adenoma components of the malignant polyp samples, while the embedded early carcinomas revealed losses of 8p, 17p, and 18, and gains of 7, 13, and 20. Aberrations detected in the adenoma components were invariably maintained in the embedded carcinomas. This approach demonstrates that using isothermally whole genome amplified FFPE DNA is technically suitable for aCGH. In addition to demonstrating the clonal origin of the adenoma and carcinoma part within a malignant polyp, the gain of chromosome arm 20q was an indicator for progression from adenoma to carcinoma.