ANATOMIC PATHOLOGY

 

Criteria For Malignancy In Gastrointestinal Endocrine Tumors

Bordi C, D'Adda T, Azzoni C, Pizzi S, Bottarelli L, Mormandi F, Antonetti T, Luong TV, Rindi G.

In contrast with the large amount of data generated from endocrine tumors of the pancreas, sparse and mostly unconfirmed data are available on the criteria for the assessment of malignancy risk and patient outcome in endocrine tumors of the gastrointestinal tract. In these conditions the 2000 WHO classification with its standardized scheme of pathologic report constitutes a framework facilitating the assessment of tumor malignancy and has been regarded as useful for clinical purposes, providing the basis for proper management of the patients and for the design of treatment protocols. The classification is based on a combination of pathological and clinical features with parameters specific for each organ in which the endocrine tumors originate. Three main categories, one further subdivided into two subgroups, are considered: (1) well-differentiated endocrine tumors, further subdivided into tumors with benign and with uncertain behavior; (2) well-differentiated endocrine carcinomas, low grade; and (3) poorly differentiated endocrine carcinomas, high grade. In this review the differential tumor characteristics between the different categories are summarized. Moreover, the relevance of additional features with respect to tumor prognostication, chiefly the Ki-67 proliferation index and malignancy-associated genetic changes, is discussed with emphasis on the discrepancies emerging between tumors of foregut and of midgut origin. 

Endocr Pathol. 2006 Summer;17(2):119-30.

 

Endocrine Tumours Of The Gastrointestinal Tract—Selected Topics

[REVIEW] 

Williams G T

This review provides an update on the pathogenesis and histopathological diagnosis of endocrine tumours of the gastrointestinal tract, concentrating on three different varieties whose careful assessment by pathologists is of particular clinical significance. These are the four types of enterochromaffin-like cell tumour of the gastric corpus, the periampullary somatostatin-containing D-cell tumour of the duodenum, and the frequently chromogranin A-negative L-cell tumour of the appendix and large intestine. In addition, the value of pathological factors in predicting the behaviour of gastrointestinal endocrine tumours and selecting therapy is discussed, and the crucial role of the pathologist in the multidisciplinary team management of these neoplasms is emphasized.

 

Histopathology, Volume 50 Issue 1 Page 30 - January 2007

Glypican 3: A Novel Marker in Testicular Germ Cell Tumors

 Zynger, Debra L., Dimov, Nikolay D., Luan, Chunyan, Tean Teh, Bin, Yang, Ximing J. 

Glypican 3 (GPC3), a membrane-bound heparin sulfate proteoglycan, may play a role in promoting embryonic cell growth and differentiation. GPC3 is mutated in Simpson-Golabi-Behmel syndrome, characterized by tissue overgrowth and an increased risk of embryonal malignancies. Recently, GPC3 was reported to be one of the over-expressed genes in testicular yolk sac tumors by gene expression microarray analysis. However, the presence of the GPC3 protein in germ cell tumors has never been investigated. The purpose of the study was to investigate the GPC3 expression in various histologic components of testicular germ cell tumors using immunohistochemistry and to assess its possible utility as a diagnostic marker. Tumors from 71 patients were examined, including components of 42 seminomas, 37 embryonal carcinomas, 24 yolk sac tumors, 20 teratomas with mature elements, 16 teratomas with immature elements, and 7 choriocarcinomas. Cytoplasmic and membranous immunoreactivity was semiquantitatively evaluated. All yolk sac tumor (24/24) and choriocarcinoma (7/7) components were immunoreactive for GPC3, whereas only 38% of teratomas with immature elements and 8% of embryonal carcinomas expressed GPC3. There was no immunoreactivity in benign testicular tissue, intratubular germ cell neoplasia, seminomas (0/42), or teratomas with mature elements (0/20). Authors conclude that the oncofetal protein GPC3 is a novel immunohistochemical marker in testicular germ cell tumors with differential expression in defined histologic subtypes. Authors findings suggest a possible role of GPC3 in tumor cell differentiation. Furthermore, GPC immunostaining may be useful in the pathologic diagnosis of nonseminomatous germ cell tumors, particularly yolk sac tumor, and choriocarcinoma. 

American Journal of Surgical Pathology. 30(12):1570-1575, December 2006.

 

Diagnosis Of Chronic Endometritis In Biopsies With Stromal Breakdown

Hannah Gilmore, Deborah Fleischhacker, Jonathan L. Hecht

Plasma cells are the hallmark of chronic endometritis but are not specific for upper tract infection. Plasma cells have also been noted in hormonally mediated endometrial disorders in association with gland architectural changes (“disordered proliferative” and “anovulatory” patterns), and stromal breakdown. We reviewed benign endometrial biopsies diagnosed at Beth Israel Deaconess Medical Center over a 2-year period described as disordered/anovulatory patterns ± stromal breakdown. Cases were excluded if tissue was not available; women were younger than 50 years where most diagnoses were atrophic or cancer; or diagnoses were secretory, menstrual endometrium, or polyps. The remaining 61 cases were compared to 33 samples of unremarkable proliferative endometrium. Plasma cells were quantified on hematoxylin and eosin–stained sections and using a histochemical stain methyl green pyronin. The indication for biopsy was an abnormal pattern of bleeding in 34 cases, infertility workup in 7, incidental part of workup for pain, or other findings in 5. The majority of disordered proliferative endometrium had plasma cells (61% grade 1, 17% grade 2) all seen on methyl green pyronin staining only. Two thirds of proliferative endometrium with breakdown showed plasma cells (19% grade 1, 39% grade 2, 10 % grade 3). Plasma cells were rare in inactive endometrium and noted in only 18% of unremarkable proliferative endometrium, all grade 1. Plasma cells are commonly present in the endometrium of women with dysfunctional uterine bleeding and focal stromal breakdown. Given the lack of clinical evidence for infection, the inflammation likely represents a physiologic process.

Human Pathology, 38;1, Jan. 2007

 

Frequency Of Barrett's Neoplasia After Initial Negative Endoscopy With Biopsy: A Long-Term Histopathological Follow-Up Study

Vieth M, Schubert B, Lang-Schwarz K, Stolte M.

BACKGROUND: Barrett's adenocarcinoma is being diagnosed increasingly. Authors examine possible differences between long segment and short-segment Barrett esophagus (LSBE and SSBE) in long-term follow-up on the basis of authors’ histopathology registry.

METHODS AND PATIENTS: All Barrett's esophagus patients diagnosed histologically between 1990 and 1995 (n = 1071) were selected. Long-term follow-up data from endoscopy with biopsy were sought on all patients without neoplasia on initial endoscopic biopsy (n = 1003). A total of 255 individuals (25.4 %) were regarded as drop-outs (201 lost and 54 without further endoscopy). Of the remaining 748 patients with follow up for more than 5 years, 315 had documented LSBE, 246 had SSBE, and 187 had no length of Barrett esophagus recorded (NLBE).

RESULTS: In the study cases (male : female ratio 2.1 : 1, mean age +/- SD 60.9 +/- 14.2 years), the biopsy procedure was fully compliant with guidelines in only 32.5 %. Only 5 cases (0.6 %) had visible lesions reported on endoscopy, but all were negative for neoplasia. Over a mean follow-up of 78.2 +/- 35.6 months (range 0-240), 7 new cases of low grade intraepithelial neoplasia (LGIN) and 15 cancer cases developed, accounting for a yearly incidence of 0.2 % (LGIN) or 0.4 % (cancer) after an initial negative endoscopy. When the cases with initial diagnosis of neoplasia were included, this yearly incidence rose to 0.5 % (LGIN), 0.3 % (high grade intraepithelial neoplasia [HGIN]) or 1.7 % (cancer). Differences between SSBE and LSBE were only encountered for cancer incidence.

CONCLUSION: The yearly incidence of Barrett esophagus cancer varies between 0.4 % and 1.7 %. Despite the limitations of this retrospective and pathology-based study, the observed risk of developing cancer in Barrett esophagus without neoplasia is comparable to that found in other studies, mainly from the US and the UK, and varies between 0.7 % and 1.0 % of yearly incidence.

Endoscopy. 2006 Dec;38(12):1201-5.

 

Barrett's Oesophagus—A Pathologist's View

 Fléjou J-F & Svrcek M

Barrett's oesophagus, a precancerous condition for oesophageal adenocarcinoma, detected on endoscopy and confirmed on histology, shows intestinal metaplasia of the lower oesophagus. The significance of microscopic foci of intestinal metaplasia at the gastro–oesophageal junction, corresponding either to so-called 'ultrashort' segment Barrett's oesophagus, or to carditis with intestinal metaplasia, is still a matter of debate. The surveillance of patients with Barrett's oesophagus is still based on systematic biopsy sampling of Barrett's mucosa on endoscopy, looking for dysplasia. Although well-established classifications of dysplasia are now used by most pathologists, there remain numerous problems with this subjective marker (sampling, diagnostic reproducibility, natural history, etc). Therefore, many alternative biomarkers have been proposed, but only DNA aneuploidy, proliferation markers and p53 loss of heterozygosity/overexpression have been shown to be of some use at the present time. Some endoscopic improvements already allow a better selection of biopsies, and it may be that in future new technologies will allow 'virtual biopsies'. On the other hand, the role of pathologists now extends to the evaluation of new therapeutic modalities of early neoplastic lesions in Barrett's oesophagus, especially endoscopic mucosal resection.

Histopathology, Volume 50 Issue 1 Page 3 - January 2007

 

 

Poorly Differentiated Tumours Of The Anal Canal: A Diagnostic Strategy For The Surgical Pathologist 

Balachandra B, Marcus V & Jass J R

Poorly differentiated malignancies affecting the anal canal are uncommon but pose diagnostic difficulties because of the wide range of normal cell types that may occur within a limited anatomical region. The range of lesions that may present as poorly differentiated tumours includes squamous cell carcinoma, adenocarcinoma, small and large cell neuroendocrine carcinoma, neuroendocrine carcinoma expressing epithelial cytokeratins and other patterns of mixed differentiation, undifferentiated carcinoma, malignant melanoma, lymphoma and secondary tumours. This review discusses the differential diagnosis of these neoplasms with the aid of short illustrative case studies.

Histopathology, Volume 50 Issue 1 Page 163 - January 2007

  

Flat Elevated Lesions Of The Colon And Rectum: A Spectrum Of Neoplastic And Nonneoplastic Entities

Gualco G, Reissenweber N, Cliche I, Bacchi CE.

The aim of this prospective study is to establish the frequency and the type (neoplastic and nonneoplastic) lesions defined endoscopically as flat elevated lesion (FEL) in the colon and rectum, as well as to compare flat adenomas (FAs) to polypoid lesions of the same size with morphometric and immunohistochemical analysis. One hundred nineteen patients were studied through fibrocolonoscopy with chromoscopy (indigo carmine spray). All detected lesions (total of 195) were removed, and FELs measuring 10 mm or smaller were also selected. Using histopathologic criteria, they were divided in neoplastic (adenomas and carcinomas) and nonneoplastic ones. In neoplastic lesions, the following parameters were evaluated to compare FAs with polypoid lesions: morphometric studies with Index of Structural Atypia (ISA) and Stratification Index (SI), evaluation of cellular proliferation with label index of Ki-67, and expression of p53 protein. Of 195 lesions resected, only 33 (17%) met the endoscopic requirements for FELs. Twelve (36.4%) were neoplastic and 21 (63.6%) considered nonneoplastic. Among the FAs, there were a percentage of high-grade (severe dysplasia) significantly more frequent than observed in polypoid lesions (16.7% vs 2.6%). In addition, the SI, Ki-67 label index and p53 positivity were significantly higher in FAs. The ISA also reached significant differences between both groups of adenomas. Non-neoplastic FELs included different entities such as hyperplasic polyps, focuses of colitis, normal mucosa, and scars. The endoscopic elements analyzed were shared between nonneoplastic FELs and FAs. A central depression, when air was properly insufflated, considered typical in neoplastic lesions, was frequently observed in nonneoplastic lesions. Following the endoscopic criteria of FELs, nonneoplastic lesions predominated over the adenomatous lesions, demonstrating that FELs and FAs are not homologous terms. The frequency of high-grade dysplasia was significantly more elevated in the adenomatous FELs than in polypoid adenomas. The ISA, SI, p53 expression, and Ki-67 label index were helpful in differentiating adenomatous FELs from polypoid lesions. Flat elevated lesions selected by endoscopic criteria are, in fact, a heterogeneous population of lesions. 

Ann Diagn Pathol. 2006 Dec;10(6):333-8.

 

 

CLINICAL PATHOLOGY 

A Technically Simple Method For Staining Of Acid-Fast Bacilli In Cytology Smears: An Evaluation

Chaturvedi S, Raheja P, Thakur R, Singh N, Arora VK, Suri V, Bhatia A.

OBJECTIVE: To study the effects of modifications in the Ziehl-Neelsen staining procedure on predictive accuracy for acid fast bacilli in comparison to the conventional technique. Simplicity of procedure and reagent economy were the factors taken into consideration.

 

DESIGN: Comparative evaluation between thick and thin air-dried smears stained conventionally and thick ethanol-fixed smears stained by the modified technique was done.

 

RESULTS: Positive predictive accuracy of all the three smears, that is, thick air-dried, thin air-dried and thick ethanol-fixed, was 100%. Negative predictive accuracy for thick air-dried, thin air-dried and thick ethanol-fixed smears was 36.36%, 32.33% and 34.78%, respectively. Overall predictive accuracy was 66.67% for thick air-dried, 61.90% for thin air-dried and 64.29% for thick ethanol-fixed. These differences were found to be statistically insignificant.

 

CONCLUSION: The modified method offers an accuracy comparable to the conventional technique, is simpler and with improved reagent economy. It is of special importance to diagnostic facilities in rural set-ups.

 Aust J Rural Health. 2006 Dec;14(6):280-3.

 

 

Best Practice In Primary Care Pathology: Review 5

[REVIEW]

Smellie, W S A, Forth, J, Ryder, S, Galloway, M J, Wood, A C, Watson, I D

This fifth best practice review examines three series of common primary care questions in laboratory medicine: (1) minor liver function test abnormalities; (2) laboratory monitoring of patients receiving lithium; and (3) investigation of possible venous thromboembolism. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus-based rather than evidence-based. They will be updated periodically to take account of new information.

Journal of Clinical Pathology, Volume 59(12), December 2006, pp 1229-1237