Sangeeta Desai

Discriminatory immunohistochemical staining of urothelial carcinoma in situ and non-neoplastic urothelium: an analysis of cytokeratin 20, p53, and CD44 antigens.

Distinction of urothelial carcinoma in situ (CIS) from reactive atypia on the basis of morphology alone may be difficult in some cases. Because this distinction is therapeutically and prognostically critical, we attempted to determine if an immunohistochemical panel would help in this differential diagnosis. The immunoprofile of 21 cases of CIS and 25 non-neoplastic urothelia (15 urothelial biopsies with reactive atypia from patients without a history of bladder cancer and 10 normal ureter sections from nephrectomies performed for renal cell carcinoma) was determined using antibodies against cytokeratin 20 (CK20), p53, and CD44 (standard isoform). In the normal urothelium CK20 showed patchy cytoplasmic immunoreactivity in only the superficial umbrella cell layer and CD44 stained only the basal cells. Nuclear immunoreactivity to p53 varied from negative to weak and patchy. Reactive urothelium also showed CK20 immunoreactivity in only the umbrella cell layer in all 15 cases, and p53 nuclear staining was predominantly negative with occasional weak positivity in the basal and parabasal intermediate cells. CD44 was overexpressed in the entire reactive urothelium in 9 cases (60%) or focally positive in intermediate cells in 6 cases (40%). In contrast, CIS showed intense CK20 and p53 positivity (81% and 57%, respectively) in the majority (>50%) of malignant cells. CD44 staining revealed residual basal cells with membranous reactivity in 44% of the cases of CIS; however, the neoplastic cells were immunonegative in all cases. At least one positive immunomarker (CK20 or p53) was abnormally expressed in all cases of CIS. Abnormal expression of CK20 (increased), p53 (increased), and CD44 (decreased) in urothelial CIS, and increased expression of CD44 in reactive atypia allows more confident distinction of urothelial CIS from non-neoplastic urothelial atypias. From a differential diagnosis perspective, use of a panel of all three antibodies with morphologic correlation would be essential.

Morphologic expressions of urothelial carcinoma in situ: a detailed evaluation of its histologic patterns with emphasis on carcinoma in situ with microinvasion.

The recently proposed World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification of flat urothelial lesions expands the definition traditionally used for urothelial (transitional cell) carcinoma in situ (CIS), basing its diagnosis predominantly on the severity of cytologic changes. Lesions now encompassed within the diagnosis of CIS exhibit an array of cytologic and architectural features, which have not been documented in detail. In this study, cases were examined with respect to histologic patterns and microinvasion (invasion into the lamina propria to a depth of less than 2 mm). Five major patterns of CIS, often occurring in the same specimen (160 patterns in 77 cases), were noted. Common to each pattern was the presence of high-grade cytologic atypia, the definitional feature. The patterns found include 1) large cell CIS with pleomorphism (57%), in which the cells had abundant cytoplasm and nuclear pleomorphism; 2) large cell CIS without nuclear pleomorphism (48%); 3) small cell CIS (14%), in which the cytoplasm was relatively scant and pleomorphism was usually minimal; 4) clinging CIS (40%), in which the urothelium was denuded with a patchy, usually single layer of atypical cells; and 5) cancerization of urothelium (16%) with either pagetoid spread (clusters or isolated single cells) or undermining or overriding of the normal urothelium. Carcinoma in situ with microinvasion into the lamina propria (13 cases: 3 of 77 CIS cases studied above and 10 additional cases) was evident as invasive cells with retraction artifact mimicking vascular invasion (77%, 10 cases); nests, irregular cords, and strands, or isolated single cells with desmoplasia (8%, 1 case); or absent stromal response (15%, 2 cases). Although the diagnostic terminology for all of these patterns, for the purposes of the surgical pathology report, should be simply urothelial CIS with no specific mention of the morphologic pattern, awareness of the histologic diversity of CIS will facilitate the diagnosis of this therapeutically and biologically critical flat lesion of the urothelium. These lesions may be associated with microinvasion, which may be clinically unsuspected and histologically subtle.

Giant cell tumor of the tendon sheath: A retrospective study of 28 cases

Background and Objectives: Giant cell tumor of the tendon sheath (GCTTS) is a lesion of uncertain etiology. To better interpret pathogenesis and aid in the differentiation of GCTTS from other similar pathological processes we reviewed the literature and analyzed the available information.

Single-Injection Depot Progesterone Before Surgery and Survival in Women With Operable Breast Cancer: A Randomized Controlled Trial

PURPOSE Many nonrandomized studies have suggested better outcome for patients with breast cancer who undergo surgery during the luteal (progestogenic) phase of their menstrual cycle, but this is controversial. We investigated the effect of a single preoperative injection of hydroxyprogesterone in women with operable breast cancer (OBC) in a randomized controlled trial (ClinicalTrials.gov identifier, NCT00123669). PATIENTS AND METHODS One thousand patients with OBC were randomly assigned to receive surgery or an intramuscular injection of depot hydroxyprogesterone 500 mg 5 to 14 days before surgery. Primary and secondary end points were disease-free survival (DFS) and overall survival (OS), respectively. An analysis by axillary lymph node status was preplanned. RESULTS At a median follow-up of 65 months among 976 eligible patients, 273 recurrences and 202 deaths were recorded. In the progesterone group versus control group, 5-year DFS and OS rates were 73.9% v 70.2% (hazard ratio [HR], 0.87; 95% CI, 0.68 to 1.09; P = .23) and 80.2% v 78.4% (HR, 0.92; 95% CI, 0.69 to 1.21; P = .53), respectively. In 471 node-positive patients, the 5-year DFS and OS rates in the progesterone group versus control group were 65.3% v 54.7% (HR, 0.72; 95% CI, 0.54 to 0.97; P = .02) and 75.7% v 66.8% (HR, 0.70; 95% CI, 0.49 to 0.99; P = .04), respectively. In multivariate analysis, DFS was significantly improved with progesterone in node-positive patients (adjusted HR, 0.71; 95% CI, 0.53 to 0.95; P = .02), whereas there was no significant effect in node-negative patients (P for interaction = .04). CONCLUSION A single injection of hydroxyprogesterone before surgery did not improve outcomes in all women with OBC. This intervention showed significant improvement in node-positive women that may be considered hypothesis generating. If replicated in other studies, this could be a simple and inexpensive intervention, especially in developing countries where the incidence of lymph node metastasis is high.

Follicular dendritic cell tumor of the parapharyngeal region.

Follicular dendritic cell (FDC) tumors are rare. A majority of the reported cases were confined to the lymph nodes. We report a case of FDC tumor occurring in the parapharyngeal region in a 45‐year‐old woman.

Estrogen, progesterone and HER2 receptor expression in breast tumors of patients, and their usage of HER2-targeted therapy, in a tertiary care centre in India

BACKGROUND This study was undertaken to document the pattern of expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptor-2 (HER2) and the usage of HER2-targeted therapy in a large tertiary care hospital in India in the year 2008. MATERIALS AND METHODS The histopathology reports of all breast cancer patients registered in the hospital in 2008 were extracted from the electronic medical record system. All the cases were immunohistochemically evaluated for estrogen and progesterone receptor status (ER and PR), and c-erbB-2 protein (HER2) expression using standard immunoperoxidase method. The use of HER2-targeted therapies was evaluated by extracting relevant information from the database of the hospital pharmacy and case charts of patients enrolled in ongoing approved trials. RESULTS A total of 2001 new patients of invasive breast cancers with available pathology reports were registered in the hospital in the year 2008. ER and/or PR expression was positive in tumors of 1025 (51.2%) patients. HER2 3+ expression by immunohistochemistry (IHC) was found in 335 (16.7%) and HER2 2+ in 163 (8.1%). The triple negative phenotype was found in 596 (29.8%) patients. An estimated 441 patients were eligible to receive HER2-targeted therapy based on their HER2 status. Of these 38 (8.6%) patients received some form of HER2-targeted therapy; 20 patients (4.5%) as part of ongoing clinical trials and 18 (4.1%) as part of routine care. CONCLUSIONS The overwhelming majority of patients eligible for HER2-targeted therapy in our institution are unable to receive it because of financial constraints and limited access to health insurance. There is a higher fraction of patients with the triple negative phenotype compared to the Western population.

Uteruslike masses of the ovary associated with breast cancer and raised serum CA 125

We describe three cases of a uteruslike mass of the ovary, a condition in which the ovary is replaced by a mass that grossly and microscopically resembles the uterus. The patients were 38, 43, and 39 years of age, and only the first was nulliparous. Two of them also had breast carcinomas. Two patients also had elevated CA 125 levels that gave rise to a clinical suspicion of ovarian malignancy. There were no anatomic abnormalities in any of the patients. The presence of residual ovarian stroma in two of the patients (both of whom had breast cancer) suggests that metaplasia rather than a congenital anomaly is the cause. Elevated CA 125 levels are consistent with the endomyometriosis nature of the lesion.

Utility of the thromboplastin-plasma cell-block technique for fine-needle aspiration and serous effusions

(I) To assess the feasibility of thromboplastin‐plasma (TP) method for cell block, (II) to concentrate the minimal cellular material from effusions and needle‐rinses by block preparation and improve visual details, (III) to compare conventional cytological smears with cell blocks for final assessment, and (IV) to assess utility of immunocytochemistry (ICC) for diagnostic accuracy.

An analysis of 46 static telecytology cases over a period of two years

We analysed 46 telecytology cases sent from two rural hospitals about 500 km from a tertiary cancer centre. The cases were submitted for second opinion over a period of two years and evaluated using a static store and forward telecytology approach. A total of 715 digital images were studied (average 15 per case). Forty-one of the 46 cases (89%) were reported within 3 days and 54% of cases were reported within one working day. The aspiration smears and images were found to be of diagnosable quality in 89 and 93% of the cases, respectively. The diagnostic concordance was assessed by comparing the telecytology diagnosis, glass slide diagnosis and final histopathology diagnosis (when available). A clinically useful diagnosis was rendered in 91% cases with 74% complete concordance. Five out of 46 cases (11%) were deferred for glass slide review. Store and forward telecytology using the Internet is a rapid and effective method of providing expert diagnosis in cytology.

Scrape cell‐block technique for fine needle aspiration cytology smears

An inconclusive diagnosis on fine needle aspiration cytology (FNAC) may be due to poor spreading and presence of thick tissue fragments despite aspiration of adequate material. Repeat aspiration may not be possible especially when aspirates of deep seated organs have been obtained by image guided techniques. We have resorted to a ‘scrape cell‐block’ (SCB) technique in such cases. In this technique the cellular material on the slides which had already been fixed and stained, was carefully removed by scraping following destaining and then processed as a cell block. SCB interpretation was then compared with the smear diagnosis and histological diagnosis, wherever available. A total of 27 cases were studied. In 12 cases SCB slides added information to the FNAC smears. In 14 cases SCB did not offer any additional information. SCB was inconclusive in one case. Final histological correlation was available in eight cases and the SCB diagnosis was confirmed in six cases, whereas in two cases SCB failed to identify the tumour. Immunocytochemistry (ICC) was done in one case. SCB is a useful technique to make the best use of the available material when reaspiration is difficult.