Lack Of Nuclear Atypia Research Articles

Biology and management of lobular endocervical glandular hyperplasia.

Lobular endocervical glandular hyperplasia (LEGH) is a multicystic proliferative disorder of the uterine cervix. The aim of this review was to clarify the current understanding of this unique tumor. This article reviews the chronological progress of research regarding clinico-pathological and genetic aspects of LEGH and related cervical cystic diseases such as Nabothian cyst and adenocarcinoma of gastric type (GAS), using the literature and data from our institute. We also describe clinical management including preoperative diagnosis and adequate surgical/expectant treatment based on the biological features. Recent studies revealed several unique aspects of LEGH, that is, (i) production of gastric mucin, (ii) symptomatic and histological similarity with minimal deviation adenocarcinoma (MDA), and (iii) frequent association with GAS, including MDA. These findings indicated that LEGH is a gastric metaplasia, as well as pre-cancerous neoplasia. For the preoperative diagnosis of LEGH, the combination of "cosmos" sign on magnetic resonance imaging, detection of gastric mucin, and lack of nuclear atypia on cytology is important. Cone biopsy is effective for pathological diagnosis. Simple hysterectomy is indicated as surgical treatment for LEGH; however, meticulous follow-up is also an option, especially for young patients, because the rate of malignant transformation was reported to be 1%-2%. For LEGH patients who selected follow-up, a worsening cytology and increase in lesion size were important signs of malignant change of LEGH for safe follow-up. Proper understanding of the characteristics of LEGH is important for adequate management.

Macrofollicular Variant of Follicular Thyroid Carcinoma (MV-FTC) with a Somatic DICER1 Gene Mutation: Case Report and Review of the Literature

Benign thyroid lesions such as multinodular goiter and adenomatoid nodules are well-circumscribed lesions displaying a macrofollicular growth pattern and lack of nuclear atypia. The highly unusual macrofollicular variant of follicular thyroid carcinoma (MV-FTC) mirrors these attributes and is thereby misclassified by cytological examination of fine-needle aspiration biopsies. The MV-FTC diagnosis is instead suggested following histological investigation, in which malignant attributes, most commonly capsular invasion, are noted. The bulk of MV-FTCs described in the literature arise in younger female patients and carry an excellent prognosis. A recent coupling to mutations in the DICER1 tumor suppressor gene has been proposed, possibly indicating aberrancies in micro-RNA (miRNA) patterns as responsible of the tumorigenic process. We describe the cytological, histological and molecular phenotype of a 35 mm large MV-FTC arising in the right thyroid lobe of a 33-year-old female with a family history of multinodular goiter. The tumor was encapsulated and strikingly inconspicuous in terms of cellularity and atypia, but nevertheless displayed multiple foci with capsular invasion. A next-generation molecular screening of tumor DNA revealed missense variants in DICER1 (p. D1709N) and MET (p. T1010I), but no established fusion gene events. After sequencing of germline DNA, the DICER1 mutation was confirmed as somatic, while the MET variant was constitutional. The patient is alive and well, currently awaiting radioiodine treatment. This MV-FTC mirrors previous publications, suggesting that these tumors carry a favorable prognosis and predominantly arise in younger females. Moreover, DICER1 mutations should be considered a common driver event in the development of MV-FTCs.

C-Kit, CD34 & α-SMA Immunohistochemical Features in Classic Kaposi Sarcoma and Kaposiform Hemangioendothelioma

Purpose & MethodsThe aim of this work was to study the clinicopathological features of Kaposi sarcoma (KS) & kaposiform hemangioendothelioma (KHE) and analyze their immunohistochemical expression of c-Kit, CD34, α-SMA. The study was performed on cutaneous 10 classic KS & 8 KHE. ResultsKHE shows several dilated lymphatic channels, focal capillary formation, lack of nuclear atypia and mitosis within tumor cells. These features help to exclude Kaposi sarcoma in spite of the kaposiform pattern of tumor cells. C-Kit was expressed by tumor cells in all KHE cases and in 60% only of KS. All elements within both tumor groups expressed CD34 antibody. α-SMA was expressed by tumor cells in 70% of KS cases and none of KHE. ConclusionC-Kit and CD34 seem to be reliable at labeling KS and KHE as they can help in diagnosis of these tumors in routinely processed tissue but they don’t differentiate between them. If α-SMA also labeled the tumor, then KHE diagnosis can be ruled out. KS & KHE exemplify stem cell tumors that could give smooth muscle cell–like phenotype in KS. Anti C-kit therapy should be tested in KS & KHE to prevent recurrence.

Squamous Metaplasia of the Peritoneum

The ability of the peritoneum to undergo metaplasia, especially to Müllerian-type epithelium has been recognized for a long time. The ability of mesothelial cells to modulate cytoskeletal filaments and shape is provided through the distinct form of subserosal cells, called multipotential subserosal cells, that have the function of replicative cells that differentiate into surface epithelium when affected by various stimuli. Rare forms of peritoneal metaplasia include squamous and cartilaginous metaplasia. This report presents a case of fully developed, mature peritoneal squamous metaplasia in an 85-year-old woman who underwent surgery because of small bowel perforation leading to diffuse peritonitis. This rare incidental finding almost always occurs in the background of chronic peritoneal irritation as a response to mesothelial injury. Squamos peritoneal metaplasia should not be interpreted as metastatic squamous cell carcinoma. The most important distinguishing criteria are the lack of nuclear atypia, mitoses, necrosis, and desmoplastic stromal response.

Entertis Cystica Profunda in Puetz-Jeghers Syndrome (PJS): A Case of Pseudo-Invasion

Purpose: 20-year-old Caucasian female with PJS with documented STK 11 mosaic mutation, underwent a wireless capsule study to evaluate abdominal pain. The capsule showed a large ileal polyp (Figure 1), biopsy of which showed a hamartoma without dysplasia, consistent with PJS. Attempts to remove the polyp endoscopically was unsuccessful due to its broad base. Patient later underwent a small bowel resection removal of 10 cm of her ileum along with the indurated broad based polyp which measured 1.5 x 1.0 cm. The pathology report determined the polyp to be a benign mucin filled cysts in the bowel wall penetrating through the mucosal layer consistent with enteritis cystica profunda (ECF). ECF are thought to arise after mucosal ulceration or inflammatory damage to the submucosa which allows outgrowth of epithelial element into other layers of the bowel wall. The histological findings of these mucin filled cysts leading the “ pseudoinvasion” (Figure 2) of the epithelial glands extending into the muscularis propia and serosa have been confused for mucin producing adenocarcinomas. Although there is an increased risk of malignant transformation in PJS, when surgical resection is required, a limited resection is recommend to minimize bowel loss. PJS polyps with epithelial misplacement can be confused with invasive cancer but the lack of nuclear atypia, normal appearing small bowel cells and lack of lymphatic invasion all serve to support the hamartomatous origin of a benign PJS polyp. Recognition of pseudo-invasion or enteritis cystica profunda of PJS polyps will prevent unnecessary surgical bowel resections.Figure: Endoscopic view of polyp.Figure: Pseudo-invasion of a Puetz-Jeghers polyp.

Transitional Cell Metaplasia of Fallopian Tube Fimbriae

Germline mutations in the hereditary breast/ovary carcinoma genes BRCA1 or BRCA2 confer increased lifetime risk for ovarian, fallopian tube, and primary peritoneal carcinoma. This risk can be minimized by prophylactic surgery. Risk-reducing salpingo-oophorectomy (RRSO) provides 2 potential benefits: long-term cancer risk reduction and immediate detection of occult early carcinoma, which frequently arises in the tubal fimbriae. Recognition of occult early tubal carcinoma is challenging because it is often microscopic in size and can be confined to the fimbrial epithelium without invasion. Transitional cell metaplasia is a benign epithelial alteration that is a common finding in the serosa of the tube but is underrecognized in the tubal fimbriae, where it may mimic tubal intraepithelial carcinoma. The aim of this study was to define the incidence, morphology, immunophenotype, and distribution of transitional cell metaplasia of the fimbriae in RRSO specimens from 96 women with BRCA germline mutations and to compare these features to those of tubal intraepithelial carcinoma in this cohort. RRSO specimens from an additional 30 women at increased risk for ovarian cancer based on strong family history were also studied, along with RRSO from 1 patient with Lynch syndrome, and 1 patient with PTEN mutation. Transitional cell metaplasia of the fimbriae was present in 26% of all RRSO specimens. It was commonly multifocal (67%), with involvement of the tip, edges, or base of the fimbrial plicae. Average size of a metaplastic focus was 1.3 mm (range: 0.1 to 10 mm). None of the metaplastic foci expressed p53 by immunohistochemistry nor was there increased staining for the proliferation marker MIB-1. Occult early carcinoma was detected in 6/128 RRSO specimens. Median tumor size was 2.7 mm (range: 1 to 11 mm). All expressed p53 and showed markedly increased MIB-1 staining. The key criteria distinguishing transitional cell metaplasia from tubal intraepithelial carcinoma were uniform cell size and shape, normal nucleus:cytoplasm ratios, lack of nuclear atypia, presence of nuclear grooves, lack of mitoses, and absence of p53 expression or increased staining for MIB-1. No particular clinical variables (BRCA 1 vs. BRCA 2 mutation, parity, personal history of breast cancer, prior abdomino-pelvic surgery, or intraoperative findings) or benign pathologic alterations in the RRSO specimens were associated with the presence of transitional cell metaplasia of the fimbriae. None of the patients with this finding developed peritoneal carcinoma during follow-up ranging from 1 month to 9 years. This study demonstrates that transitional cell metaplasia of the fimbriae is a common benign finding in RRSO specimens that should not be confused with the much less common finding of tubal intraepithelial carcinoma.

Retroperitoneal Xanthogranuloma in a Patient with Erdheim-Chester Disease

A case of Erdheim-Chester disease with retroperitoneal and renal sinus xanthogranuloma that occurred in a 50-year-old woman is presented. The 12 previously reported cases of Erdheim-Chester disease associated with retroperitoneal xanthogranuloma are reviewed and compared with 13 sporadic cases of retroperitoneal xanthogranuloma. Retroperitoneal xanthogranuloma is distinguished from inflammatory malignant fibrous histiocytoma by its lack of neutrophils, inconspicuous vascularity, lack of nuclear atypia, and abundant collagen. It is distinguished from inflammatory fibrosarcoma by its numerous foamy histiocytes, relative lack of plasma cells, and lack of nuclear atypia; it is distinguished from retroperitoneal fibrosis principally by its many foamy histiocytes, lack of plasma cells, and lack of vasculitis.