Standardised reporting protocol for endoscopic resection for Barrett oesophagus associated neoplasia: expert consensus recommendations.

Endoscopic resection (ER) is considered the therapy of choice for intraepithelial neoplasia associated with visible lesions and T1a adenocarcinoma. Pathologists are bound to encounter specimens collected via these techniques more frequently in their practice. A standardised protocol for handling, grossing, and assessing ER specimens should be adopted to ensure that all prognostic information and characteristics influencing treatment are included in reports (see Supplementary Video Abstract, http://links.lww.com/PAT/A22). The entire specimen should be appropriately oriented, processed and assessed. An ER specimen will commonly show intraepithelial neoplasia or invasive carcinoma. There are essential features that should be recorded if invasive carcinoma is found as they dictate further management and follow-up. These features are the margin status, depth of invasion, degree of differentiation and presence or absence of lymphovascular invasion. Important features such as duplication of muscularis mucosae should be recognised to avoid misinterpretation of depth of invasion. Key diagnostic and prognostic elements that are essential for optimal clinical decisions have been included in the reporting format proposed by the Structured Pathology Reporting committee of the Royal College of Pathologists of Australasia (RCPA).

Endoscopic biopsy features and diagnostic challenges of adult Crohn's disease at initial presentation.

AIMS: Endoscopic biopsy diagnosis of Crohn's disease (CD) is problematic due to lack of specific microscopic features and patchy involvement. There is no documentation of the pattern and severity of microscopic features of CD at initial presentation in adults or children. We aimed to assess the initial mucosal biopsy features of CD in adults and to identify any specific features to confirm the diagnosis. METHODS: Thirty sets of initial, adult endoscopic biopsies suspected to be CD with subsequent resections, repeat biopsies with long-term follow-up, and/or other confirmatory laboratory results were analysed by three gastrointestinal pathologists, blinded for the final diagnosis for mucosal architectural changes, epithelial abnormalities, chronic and active inflammation and changes of muscularis mucosae and submucosa. There were 25 cases of CD and five cases of non-CD for comparison (3 tuberculosis and 2 right-sided diverticular disease and associated colitis). Cases confirmed as ulcerative colitis were excluded, as diagnostic challenges are already well established. RESULTS: The majority of initial biopsies (96%) of CD were abnormal with active chronic ileocolitis with a very high proportion (80%) showing the classic combination of abnormal mucosal architecture, epithelial abnormalities and active chronic inflammation. The most sensitive feature was lamina proprial chronic inflammation (sensitivity 92.7%). Sensitivity for other features was as follows: active inflammation 87.8%, basal plasmacytosis 82.1%, architectural changes 80.5% and epithelial abnormalities 70.7%. Abnormalities were found in 94% of ileal and 76% of colonic biopsies. No feature was specific as all tuberculosis and diverticular disease cases showed the classic combination. Granulomata were seen in 10 of 41 CD, in all five tuberculosis and in no diverticular disease biopsies. Small, tight, well defined granulomata characterised CD over large coalesced ganulomata of tuberculosis. Paneth cell and pseudopyloric metaplasia was seen only in CD (2/25). CONCLUSIONS: Initial endoscopic biopsies of adult CD are significantly abnormal and a majority shows active chronic ileocolitis. The features are sufficiently important to suspect CD at initial presentation in the appropriate clinical setting. Tuberculosis and diverticular disease associated colitis are two important mimics to consider in addition to ulcerative colitis.

Duodenal adenocarcinoma arising from a pyloric gland adenoma with a brief review of the literature.

Pyloric gland-type adenoma of the duodenum with documented malignant progression is rare. A case is presented of an 87-year-old man with bloating and nausea, who on investigation was found to have a polyp on the anteroinferior wall of the duodenal cap. Histologic examination of the polyp showed features of a pyloric gland adenoma (PGA) demonstrating the full spectrum of progression from low- to high-grade dysplasia and finally invasive adenocarcinoma. The carcinoma showed gastric-type differentiation highlighted by its mucin immunohistochemistry profile and was of advanced stage with lymph node metastasis. The literature on PGAs and the little documentations on progression to carcinoma in duodenal PGAs are reviewed.

Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of function.

BACKGROUND: Hereditary mixed polyposis syndrome (HMPS) is characterised by colonic polyps of mixed histological types that are autosomal dominantly inherited and eventually lead to colorectal cancer (CRC). Study of the molecular basis of HMPS will enhance our knowledge of the genetic basis of the mixed polyposis-carcinoma sequence in both hereditary and sporadic CRC. METHODS/RESULTS: We performed a genomewide linkage search on 15 members of a three-generation HMPS family using the GeneChip Human Mapping 10K Array and identified a 7 cM putative linkage interval on chromosome 10q23. Subsequently, 32 members from two HMPS families were typed with nine microsatellite markers spanning the region and the linkage was confirmed with a maximum multi-point logarithm of the odds (LOD) score of 4.6 (p<0.001). The 10q23.1-10q23.31 haplotypes segregate with the disease in both families. We screened for mutations in four candidate genes within the linkage region and identified an 11 bp deletion in the bone morphogenesis protein receptor 1A (BMPR1A) gene in one family. CONCLUSIONS: Our results indicate that BMPR1A mutation accounts for HMPS. The data suggest that inactivating BMPR1A can initiate colorectal tumourigenesis via the mixed polyposis-carcinoma sequence.

Correlation of histology with anorectal function following stapled hemorrhoidectomy.

INTRODUCTION: The inadvertent removal of smooth muscle during the use of stapled hemorrhoidectomy had raised concerns about its effects on postoperative anorectal function. We correlated the amount of smooth muscle removed with anorectal function in the early postoperative period. METHODS: Patients were assessed preoperatively with an Eypasch quality-of-life questionnaire and underwent anorectal manometry and physiology testing. This was followed by a similar examination at three months postoperatively. Patients were operated on by a single surgeon and the excised anorectal mucosa was sent for histologic examination. The amount of smooth muscle excised was expressed semiquantitatively as a percentage of the total tissue removed. RESULTS: Sixty-eight patients (33 males) were recruited prospectively, with median age of 44 years. Six patients were lost to follow-up. Removal of anal transitional zone did not increase the incidence of incontinence. Both median preoperative and postoperative continence scores were good. Only one patient had incontinence to gas as a result of the operation. Median preoperative and postoperative quality-of-life scores were 114 and 131, respectively, out of a total of 144, the higher postoperative scores showing an improvement. Correlation of quality-of-life scores and mean resting anal pressures with percentage of smooth muscle removed did not show any statistical significance. CONCLUSIONS: Some smooth muscle will invariably be excised in stapled hemorrhoidectomy but the amount of smooth muscle removed did not significantly affect the continence score, quality of life, or mean anal resting pressure after stapled hemorrhoidectomy. It remains a safe and preferred procedure for the treatment of hemorrhoids.

"Tap sign" in tuberculoid and borderline tuberculoid leprosy.

Deep pain upon percussion of lesions over bone in tuberculoid leprosy, in spite of superficial sensory impairment, has been described as the "Tap Sign" (TS). This study was conducted to identify possible causes for this phenomenon and to determine the sensitivity and specificity of this sign in leprosy patients with lesions overlying bone. In 37/53 patients with lesions over bone, the sensitivity of the TS was 66.7% and the specificity was 100%. The positive predictive value was 100%, and the negative predictive value was 75%. The Tap Sign appears to be a useful clinical sign in diagnosis of tuberculoid and borderline tuberculoid leprosy where a lesion overlies a bone (sensitivity 66.7%). This test could be very useful to increase the clinical diagnostic yield, in the global perspective, in places where leprosy is diagnosed and treated by healthcare workers and primary care physicians without other laboratory facilities. Possible mechanisms responsible for the deep pain are discussed.

Cytohistologic features of invasive micropapillary carcinoma in a young female.

Invasive micropapillary carcinoma (IMPC) is a recently reported variant of breast carcinoma in women. There has been only a single report describing the cytologic features of IMPC in the literature. We report on the cytohistologic features of IMPC with diffuse involvement of two quadrants of the breast and axillary lymph node metastases in a 32-yr-old female. The cytologic appearance of IMPC was characterized by high cellularity, marked cell discohesion, and epithelial cells forming aggregates, morules, and angular and papillary clusters without fibrovascular cores and showing high nuclear/cytoplasmic ratio, irregular nuclear contours, and finely stippled chromatin. Occasional psammoma bodies were noted. Histologic examination showed a pure IMPC composed of clusters, morules, and aggregates of malignant epithelial cells surrounded by distinctly clear spaces separated by thin fibrovascular septa. The tumor involved both inner quadrants and axillary lymph nodes. A primary tumor elsewhere, particularly in the ovaries, was excluded. The patient has been disease-free 38 mo after the initial diagnosis.

Itraconazole pulse therapy in chromoblastomycosis.

Although daily itraconazole has been used effectively in chromoblastomycosis, there is no record of pulse therapy for chromoblastomycosis. A 68-year-old woman with a history of slowly enlarging scaly plaque involving the left shoulder and lateral chest, presented to the dermatology clinic at General Hospital, Kalutara, Sri Lanka. Clinically chromoblastomycosis was suspected. Direct KOH smears showed sclerotic bodies and histology showed granulomata with characteristic brown spores. Itraconazole (Sporanox) 200 mg. b.i.d. orally was given for a week followed by 3 drug free weeks. This cycle was repeated for 6 months (i.e. 7 pulses). Clinical improvement was visible by 2 months. Scrapings and biopsy repeated 5 months after the commencement of treatment were negative for chromoblastomycosis. The lesion had clinically healed by 5 months. Examination 8 months after cessation of treatment did not show any recurrence. Itraconazole pulse therapy is cheaper than daily treatment but effective in chromoblastomycosis. The optimal dosage and end point of treatment need to be ascertained after a larger study.

Tangles in smears of granulomatous lymphadenitis--a clue to the diagnosis.

OBJECTIVE: To assess the significance and nature of tangles in fine needle aspiration biopsy (FNAB) smears of granulomatous lymphadenitis. METHODS: The study group included 45 cases of clinically suspected granulomatous lymphadenitis particularly of tuberculous origin in which a cytologic diagnosis of granulomatous lymphadenitis (GL) was made on FNAB material. Smears of 21 lymph node aspirates without cytologic evidence of granulomatous disease (NGL) were included as a control group. One case with double pathology was excluded. All smears were fixed in 95% alcohol and stained with haematoxylin and eosin. Tangles were defined as a meshwork of haematoxyphilic string-like material occurring in a tangle in an otherwise well preserved smear. A score was given for the distribution (0-3) and density (1-3) of the tangles on the count of 10 high power fields for each aspirate. Statistical analysis was done by the Mann Whitney U test. RESULTS: Tangles were present in 41 of 45 (91%) GL and 7 of 21 (33%) NGL. The differences were statistically significant (p = 0.0008 and 0.0001 for distribution and density respectively). Six of the seven (84%) NGL with tangles were either cytologically diagnostic or suspicious of malignancy with 5 (71%) showing features of non-Hodgkin's lymphoma. The tangles were positive for nuclear stains (Feulgen) and originated in the nuclei of both lymphocytes and epithelioid cells, probably due to easy fragility of altered nuclear material. CONCLUSION: The presence of tangles in smears should raise the possibility of GL in the absence of a malignancy, specifically a lymphoma. This becomes an important diagnostic clue especially in situations where epithelioid histiocytes, the hall mark of GL, are sparse or absent in cytologic material.

Pitfalls in cytological diagnosis of autoimmune thyroiditis.

The aims of this study are to document pitfalls in cytologic diagnosis of autoimmune thyroiditis (AT) and highlight possible ways to minimize them. One hundred consecutive thyroid aspirates with features diagnostic or suggestive of AT, performed and reported by the first author, were included in the study. Follow-up was traced and cytologic features responsible for indecisiveness were re-assessed in those reported as suggestive of AT. The features were then correlated with the results of serologic and thyroid function tests and clinical features, and an attempt was made to amend the final diagnosis using an integrated approach. Seventy eight were diagnostic and 22 were suggestive of AT. In the latter 22, features responsible for the indecisiveness were: cytologic atypia, in the form of nuclear enlargement, irregularity and grooves and altered chromatin texture, in 14 (64%); nucleoli with suspicion of a coexisting neoplasm in three (13.6%), two of which showed epithelial preponderance, crowding and discohesion; sparse inflammation in four (18%); a predominant lymphoid population without epithelial cells resembling a reactive lymph node in one (4.5%); co-existing toxic features in two (9%); and scanty smears in one (4.5%). Eighteen of the 22 suspected of AT had follow-up. Six had been assessed histologically; three with features suspicious of a neoplasm were diagnosed respectively as a papillary carcinoma (PC), Hurthle cell carcinoma (HCC) and a multinodular goitre (MNG) with degenerate changes. The other three were confirmed as AT; one with cytologic atypia, one with sparse inflammation and the third as cytologically resembling a reactive lymphnode. In ten of the remaining 12, the final diagnosis could be revised following an integrated approach with possible reduction of the indecisiveness. Potential pitfalls are: cytologic atypia occurring in AT; abundance or scarcity of background inflammation; low cell yield; and co-existing toxicity and malignancies. Epithelial preponderance over inflammation, nuclear crowding, severe atypia and cell discohesion should raise the possibility of a neoplasm in spite of other features of AT. Awareness of possible pitfalls and adopting an integrated approach, especially in difficult situations, will minimize pitfalls.

Cytomorphologic features of diffuse sclerosing variant of papillary carcinoma of the thyroid. A report of two cases in children.

BACKGROUND: Diffuse sclerosing papillary carcinoma (DSPC), a variant of papillary carcinoma of thyroid, needs to be differentiated from classical papillary carcinoma and other variants. This variant is characterized by diffuse involvement of one or both thyroid lobes showing such histologic features as prominent sclerosis, an intense lymphocytic infiltrate, numerous psammoma bodies and squamous metaplasia together with the characteristic cytoarchitectural pattern of classical papillary carcinoma. Histologic and immuno-histochemical features have been described in previous publications. Although cytologic features of several variants of papillary carcinoma have been described previously, those of DSPC have not been widely published. The present report is on the cytomorphologic pattern of DSPC in two children, further highlighting the special features. CASES: A boy, aged 11 years, presented with diffusely nodular, firm enlargement of the thyroid gland with many palpable lymph nodes, and a girl, aged 12 years, presented with diffusely nodular, firm enlargement of the left lobe with a prominent nodule on the lower pole. Fine needle aspiration biopsy (FNAB) smears stained with hematoxylin and eosin showed numerous psammoma bodies, many lymphocytes, metaplastic squamous cells and absent stringy colloid together with epithelial cells showing classical features of papillary carcinoma, such as nuclear grooves, intranuclear inclusions and papilloid structures. Histologic examination of the thyroidectomy specimens showed features of diffuse sclerosing variant of papillary carcinoma. CONCLUSION: A diagnosis of DSPC should be considered when a combination of clinicocytologic features consisting of numerous psammoma bodies, lymphocytes, squamous metaplasia and absence of stringy colloid are noted with otherwise typical cytoarchitectural features of papillary carcinoma in FNAB smears obtained from diffusely nodular, firm thyroid enlargement.

Non-diagnostic smears in aspiration cytology of palpable breast lumps.

The cytologic diagnoses of a wide variety of breast diseases have been described in the literature and cytologic appearances of some of these are not characteristic. Technical problems during aspiration and smear preparation influence the final diagnosis, therefore, even at best hands a non-diagnostic category is to be expected. The objectives of this study were to determine the frequency of non-diagnostic reports and to assess the source of indecisiveness. This study is based on a retrospective analysis of breast aspirates signed out by the first author over a period of 18 months. The smears with non-diagnostic reports were correlated with the available histologic follow-up to identify the problem area. Forty-eight (9.1%) out of the 527 samples were non-diagnostic and within the recorded range of 6.9% to 20%. Of those 48 in the non-diagnostic category, 30 (62.5%) had histological follow-up. There were 11 (36.7%) malignant lesions and 19 (63.3%) benign lesions. In 23 cases (77%) pure interpretative problems and in 3 cases (10%) pure technical problems were responsible for the non-diagnostic reports. In 4 cases (13%) both factors contributed to the non-diagnostic report. Thirteen of the 30 (43%) lesions were cytologically suspected to be malignant. Of these 13.9 (69%) were found to be malignant while only 4 were benign; thus non-diagnostic but suspicious lesions are more likely to be malignant. The commonest cytologic features responsible for problems at interpretation were high cellularity (37%), cell discohesion (30%), large nuclei and nucleoli (30%) and the small size of the cells (40%). Inadequate or low cell yield (86%), inadequate clinical history (14%) and poor staining (14%) contributed to technical problems. The cytologic diagnosis of breast lesions such as fibromatosis, complex sclerosing lesions, papillary lesions, angiosarcoma and low nuclear grade in situ and invasive carcinomas can be difficult and the cytologic criteria for these diagnoses need further evaluation.

Cytology of granulomatous mastitis.

OBJECTIVE: To examine the cytologic features of granulomatous mastitis. STUDY DESIGN: Cytologic features of granulomatous mastitis (GM) are described as found on retrospective analysis of hematoxylin and eosin (H&E)-stained smears of nine breast lesions: eight fine needle aspiration biopsies and one imprint smear. All nine lesions were histologically confirmed. RESULTS: The aspirates were moderate or abundant. The H&E smears showed a distinctly inflammatory background with multinucleated giant cells (both foreign body and Langhans type), debris, neutrophils, macrophages, epithelioid cells and reactive epithelial cells. Special histochemical stains did not reveal any specific organisms. No foamy cells or caseation was seen. The four patients who presented for follow-up were free of disease after a minimum of 6 and maximum of 38 months. CONCLUSION: Although there are many entities mimicking GM, the cytologic pattern--consisting of multinucleated giant cells, debris, neutrophils, macrophages, epithelioid cells and reactive epithelial cells in the absence of foamy cells, caseation and demonstrable organisms--should prompt a diagnosis of GM.