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Concept: Anatomical pathology

196

Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. Serous tubal intra-epithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~ 50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues. The most significant focal DNA SCNAs were shared between cases with and without STIC lesions. The RNA sequence and the miRNA data did not identify any clear separation between cases with and without STIC lesions. HGSCs had molecular profiles more similar to normal fallopian tube epithelium than ovarian surface epithelium or peritoneum. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases.High-grade serous carcinomas (HGSCs) are associated with precursor lesions (STICs) in the fallopian epithelium in only half of the cases. Here the authors report the molecular analysis of HGSCs with and without associated STICs and show similar profiles supporting a common origin for all HGSCs.

Concepts: Cancer, RNA, Epithelium, Anatomical pathology, Carcinoma, Adenocarcinoma, Tubal ligation, Surface epithelial-stromal tumor

171

Spinal ligaments, such as the ligamentum flavum (LF), are prone to degeneration and iatrogenic injury that can lead to back pain and nerve dysfunction. Repair and regeneration strategies for these tissues are lacking, perhaps due to limited understanding of spinal ligament formation, the elaboration of its elastic fibers, maturation and homeostasis. Using immunohistochemistry and histology, we investigated murine LF elastogenesis and tissue formation from embryonic to mature postnatal stages. We characterized the spatiotemporal distribution of the key elastogenic proteins tropoelastin, fibrillin-1, fibulin-4 and lysyl oxidase. We found that elastogenesis begins in utero with the microfibril constituent fibrillin-1 staining intensely just before birth. Elastic fibers were first detected histologically at postnatal day (P) 7, the earliest stage at which tropoelastin and fibulin-4 stained intensely. From P7 to P28, elastic fibers grew in diameter and became straighter along the axis. The growth of elastic fibers coincided with intense staining of tropoelastin and fibulin-4 staining, possibly supporting a chaperone role for fibulin-4. These expression patterns correlated with reported skeletal and behavioral changes during murine development. This immunohistochemical characterization of elastogenesis of the LF will be useful for future studies investigating mechanisms for elastogenesis and developing new strategies for treatment or regeneration of spinal ligaments and other highly elastic tissues.

Concepts: Liver, Anatomical pathology, Histology, Osteoarthritis, Immunohistochemistry, Staining, Ligament, Microtome

170

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 SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1688552293761001.

Concepts: Cancer, Oncology, Mucous membrane, Anatomical pathology, Adenocarcinoma, Esophagus, Lamina propria, Muscularis mucosae

168

Purpose: Imaging features and clinical characteristics of degenerated leiomyoma in patients referred for uterine fibroid embolization (UFE) were analyzed to assess the incidence of degenerated leiomyoma. Materials and Methods: Patients referred for UFE between 2008 and 2009 were retrospectively analyzed (n=276). Patients ranged in age from 27 to 51 years (mean 38.0 years). All patients underwent screening MRI with contrast enhancement. Medical histories and clinical symptoms were evaluated. Results: Among the 276 patients who underwent MRI, 14 (5.1%) showed degenerated leiomyomas. Symptoms were abdominal pain (n=4, 26.7%), menorrhagia (n=5, 35.7%) and bulk-related symptoms (n=5, 35.7%) and no symptoms (n=5, 35.7%). Of the 14 patients with degenerated leiomyomas, 5 (42.9%) had a history of pregnancy in the past two years. For T1-weighted imaging (T1WI), a high signal intensity (SI) of the leiomyoma was the most common finding (n=9, 64.3%) and a hyperintense rim (n=4, 28.6%) was the second most common. On T2-weighted imaging (T2WI), a low SI of the leiomyoma was found in six patients (42.9%), a high SI in four (28.6%) and a heterogeneous SI in four (28.6%) patients. Conservative management was performed in 11 (78.6%) patients, surgery in 3 (21.4%) and uterine artery embolization in one (7.1%) patient. Conclusion: The incidence of degeneration of leiomyoma in patients referred for UFE was 5.1%. Patients presented with variable clinical symptoms with or without a history of pregnancy. MR imaging showed a high SI on T1WI and various SIs on T2WI without contrast enhancement. An understanding of the degeneration of leiomyomata is essential when considering UFE.

Concepts: Uterus, Anatomical pathology, Radiology, Gynecology, Uterine fibroids, Leiomyoma, Myometrium, Uterine artery embolization

168

SOFT TISSUE TUMORS ARE CLASSIFIED ACCORDING TO THEIR HISTOLOGICAL RESEMBLANCE TO NORMAL ADULT TISSUES AND CAN BE GROUPED INTO THE FOLLOWING CATEGORIES BASED ON METASTATIC POTENTIAL: benign, intermediate (locally aggressive), intermediate (rarely metastasizing) and malignant. Over the past two decades, considerable progress has been made in our understanding of the genetic background of soft tissue tumors. Traditional laboratory techniques, such as cytogenetic analysis and fluorescence in situ hybridization (FISH), can be used for diagnostic purposes in soft tissue pathology practice. Moreover, cytogenetic and molecular studies are often necessary for prognostics and follow-up of soft tissue sarcoma patients. This review provides updated information on the applicability of laboratory genetic testing in the diagnosis of benign and intermediate soft tissue tumors. These tumors include nodular fasciitis, chondroid lipoma, collagenous fibroma (desmoplastic fibroblastoma), giant cell tumor of tendon sheath (GCTTS)/pigmented villonodular synovitis (PVNS), angiofibroma of soft tissue, myxoinflammatory fibroblastic sarcoma (MIFS) and ossifying fibromyxoid tumor (OFMT).

Concepts: Genetics, Cancer, Oncology, Extracellular matrix, Soft tissue sarcoma, Anatomical pathology, Fluorescent in situ hybridization, Cytogenetics

168

Dermatofibrosarcoma protuberans is a locally aggressive mesenchymal neoplasm. It usually presents as an indurated plaque that protrudes above the surface of the skin. Some patients have clinically persistent plaques that might be atrophic. The atrophic variant of dermatofibrosarcoma protuberans may be confused with some common skin diseases with atrophic appearance. We reported a 40-year-old woman who had a 10-year history of an atrophic dermatofibrosarcoma protuberans. Molecular analysis showed a fusion between COL1A1 exon 31 to exon 2 of PDGFB. The lesion was totally excised, with negative margins of the resection demonstrated by CD34 immunostaining. To our knowledge, this is the second case of atrophic dermatofibrosarcoma protuberans confirmed by detection of COL1A1-PDGFB fusion gene. This appears to be the first report of a fusion between COL1A1 exon 31 to exon 2 of PDGFB in atrophic dermatofibrosarcoma protuberans. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1249657688795311.

Concepts: DNA, Oncology, Anatomical pathology, Chromosomal translocation, Dermatofibrosarcoma protuberans, PDGFB, CD34, Dermatofibrosarcoma

167

Formalin fixation is a mainstay of modern histopathologic analysis, yet the practice is poorly standardized and a significant potential source of preanalytical errors. Concerns of workflow and turnaround time drive interest in developing shorter fixation protocols, but rapid protocols can lead to poor histomorphology or inadequate downstream assay results. Additionally, assays such as immunohistochemistry for phosphorylated epitopes have historically been challenging in the context of formalin-fixed tissue, indicating that there may be room for improvement in this process that is fundamental to the practice of anatomic pathology. With these issues in mind, we studied basic formalin biochemistry to develop a novel formalin fixation protocol that involves a pre-incubation in subambient temperature formalin prior to a brief exposure to heated formalin. This new protocol is more rapid than standard protocols yet preserves histomorphology and yields tissue that is compatible with an expanded set of downstream clinical and research assays, including immunohistochemistry for phosphorylated epitopes.

Concepts: Biology, Pathology, Anatomical pathology, Histology, Histopathology, Greek loanwords, Immunohistochemistry, Formaldehyde

167

The most compelling reason and primary goal of treating actinic keratoses is to prevent malignant transformation into invasive squamous cell carcinoma, and although there are well established guidelines outlining treatment modalities and regimens for squamous cell carcinoma, the more commonly encountered precancerous actinic lesions have no such standard. Many options are available with variable success and patient compliance rates. Prevention of these lesions is key, with sun protection being a must in treating aging patients with sun damage as it is never too late to begin protecting the skin.

Concepts: Cancer, Medical terms, Anatomical pathology, Squamous cell carcinoma, Squamous epithelium, Prevention, Skin cancer, Actinic keratosis

166

OBJECTIVE: To clearly define the proportions of benign vs malignant histologic findings in resected renal masses through an in-depth review of the contemporary medical data to assist in preoperative risk assessment. MATERIALS AND METHODS: PubMed and select oncology congresses were searched for publications that identify the histologic classification of resected renal masses in a representative sample from the contemporary data: [search] incidence AND (renal cell carcinoma AND benign); incidence AND (renal tumor AND benign); percentage AND (renal cell carcinoma AND benign); limit 2003-2011. RESULTS: We identified 26 representative studies meeting the inclusion criteria and incorporating 27,272 patients. The frequency of benign tumors ranged from 7% to 33%, with most studies within a few percentage points of the mean (14.5% ± 5.2%, median 13.9%). Clear cell renal cell carcinoma occurred in 46% to 83% of patients, with a mean of 68.3% (median 61.3; SD = 11.9%). An inverse relationship between tumor size and benign pathologic features was identified in 14 of 19 (74%) studies that examined an association between tumor size and pathologic characteristics. A statistically significant correlation between clear cell renal cell carcinoma and tumor size was identified in 13 of 19 studies (63%). The accuracy of preoperative cross-sectional imaging was low in the 2 studies examining computed tomography (17%). CONCLUSION: Benign renal tumors represent ∼15% of detected surgically resected renal masses and are more prevalent among small clinical T1a lesions. Noninvasive preoperative differentiation between more and less aggressive renal masses would be an important clinical advance that could allow clinicians greater diagnostic confidence and guide patient management through improved risk stratification.

Concepts: Cancer, Oncology, Statistics, Anatomical pathology, Benign tumor, Tumor, Standard deviation, Renal cell carcinoma

163

The diagnosis of breast lesions is usually confirmed by fine-needle aspiration cytology (FNAC) or histological biopsy. Although there is increasing literature regarding the advantages and limitations of both modalities, there is no literature regarding the accuracy of these modalities for diagnosing breast lesions in high-risk patients, who usually have lesions detected by screening. Moreover, few studies have been published regarding the cytopathology of mammary tumors in cats despite widespread use of the animal model for breast cancer formation and inhibition. The objective of the present study was to evaluate the diagnostic interest of cytological and histopathological analysis in feline mammary tumours (FMTs), in order to evaluate its possible value as an animal model.

Concepts: Cancer, Breast cancer, Pathology, Anatomical pathology, Breast, Needle aspiration biopsy, Mammary gland, Mammary tumor