Sunati Sahoo

Expression of Alpha-Methylacyl-CoA Racemase in Papillary Renal Cell Carcinoma

Alpha-methylacyl-CoA racemase (AMACR) was first discovered by using cDNA microarray technology as a molecular marker for prostate cancer. Our recent microarray analysis of renal cell carcinomas showed a significant increase of AMACR mRNA levels in papillary renal cell carcinomas, but not in other subtypes. To investigate the value of this marker in pathologic diagnosis, we analyzed AMACR mRNA levels in cDNA microarrays from 70 kidney tumors. Furthermore, we evaluated the AMACR expression in 165 kidney tumors on tissue microarrays and 51 papillary carcinomas of other organs by immunohistochemistry. AMACR mRNA was significantly overexpressed in 7 of 8 papillary renal cell carcinomas with an average of 5.2-fold increase, and only in 2 of 62 nonpapillary kidney tumors. Immunohistochemistry demonstrated strong AMACR positivity in all cases of papillary renal cell carcinomas (41 of 41, 100%), including 6 metastatic papillary renal cell carcinomas, but only focal or weak reactivity in the minority (18 of 124, 15%) of other renal tumors including 13 of 52 clear cell renal cell carcinomas, 3 of 20 oncocytomas, and 2 of 17 urothelial carcinomas. All chromophobe (0 of 18) and sarcomatoid components of renal cell carcinomas (0 of 15) were negative for AMACR. Weak or focal AMACR immunoreactivity was detected in only 4 of 51 (8%) papillary carcinomas arising in other organs (2 of 14 thyroid, 2 of 13 lung, 0 of 6 breast, 0 of 6 endometrium, 0 of 6 ovary, and 0 of 6 pancreas). Using a combination of cDNA microarrays, tissue microarrays, and immunohistochemistry, we identified AMACR as a marker for papillary renal cell carcinoma, which could be valuable in subclassification of renal cell carcinomas and in the differential diagnosis of a metastatic papillary carcinoma.

Cytokeratin 19 immunoreactivity in the diagnosis of papillary thyroid carcinoma: a note of caution.

To evaluate the expression of cytokeratin (CK) 19, we stained sections obtained from formalin-fixed, paraffin tissue blocks of 35 thyroid tumors (follicular adenoma [FA], 20; papillary thyroid carcinoma [PTC], 10 follicular variant [FV] and 5 usual type) and scored the extent of staining as follows: 1+ (<5% positively stained cells), 2+ (5%-25% positively stained cells), 3+ (25%-75% positively stained cells), and 4+ (>75% positively stained cells). All 15 PTCs (including 10 FV-PTCs) were CK19 positive: 14 were 4+ and 1 (FV-PTC) was 2+. All 20 FAs also were CK19 positive: 15 were 1+, 1 was 2+, 4 were 3+, and none was 4+. In the FAs that were scored 1+, reactivity usually was confined to follicular cells lining cystically dilated atrophic follicles that lacked the typical nuclear features of PTC. The remaining FAs showed more diffuse reactivity, which was, however, less intense than that observed in the PTCs. Thus, immunoreactivity for CK19 is not specific for PTC, although we acknowledge that the extent and intensity of staining are considerably greater in this tumor than in FA. There were no significant differences in staining for CK19 between nonneoplastic follicles adjacent to PTCs and those adjacent to FAs.

Triad of Columnar Cell Alteration, Lobular Carcinoma in Situ, and Tubular Carcinoma of the Breast

Abstract:  Columnar cell alteration in the breast encompasses a spectrum of pathologic changes ranging from simple columnar cell change to more complex columnar cell hyperplasia with and without atypia to in situ carcinoma, often with a micropapillary architecture. For reasons that remain unclear, the columnar cell lesions are associated with tubular carcinomas and lobular carcinoma in situ. Therefore it is important to be familiar with the spectrum of changes and the associated lesions, especially in breast core biopsies for further management. 

Defining negative margins in DCIS patients treated with breast conservation therapy: The University of Chicago experience

Abstract:  Management of ductal carcinoma in situ (DCIS) has been evolving and the majority of women are now being treated with breast‐conserving surgery and radiation therapy (i.e. breast conservation therapy [BCT]). Controversies still exist regarding the histologic features and margin status that are associated with local recurrence. The goal of this study was to review our institutions experience in patients diagnosed with DCIS and treated with BCT to determine pathologic features that can predict local recurrence, with particular emphasis on the final surgical margin status. We analyzed 103 consecutive patients with DCIS who were treated with BCT between 1986 and 2000. The slides were reviewed to determine the final margin status, type of DCIS, size of DCIS, nuclear grade, presence of necrosis and calcification, and volume of excised specimen. Margins were considered positive when DCIS touched or was transected at an inked margin. Negative margins were further categorized as close (less than 1 mm), 1–5 mm, and more than 5 mm. The size of the DCIS was determined based on either the maximal dimension on a slide or from the number of consecutive slides containing DCIS. Morphology and immunohistochemical profiles of the recurrent DCIS cases were compared with original DCIS. All patients were treated uniformly with external beam radiation therapy to the entire breast (median dose 46 Gy) with a boost to the tumor bed (median dose 14 Gy). The median follow‐up was 63 months (range 7–191 months). The actuarial 5‐year local control rate was 89%. The median time to local recurrence was 55 months. There were 13 local recurrences, of which 9 recurred as pure DCIS and 4 as invasive ductal carcinomas. Univariate analysis showed a significant association with local recurrence for positive margin (p = 0.008), high nuclear grade (p = 0.02), and young age at diagnosis (p = 0.03). If margins were negative, the 5‐year local control was 93%, as compared to 69% if margins were positive. A multivariate analysis showed that early age at diagnosis, positive margin status, and high nuclear grade were independently associated with local recurrence. The morphology and immunohistochemical stains of all nine recurrent DCIS were similar to those of the original DCIS. Breast conservation can be achieved with excellent local control by obtaining microscopically negative margins as strictly defined by DCIS not touching the inked surgical margins, and postoperative radiation that includes boost therapy to the tumor bed.

Dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa is one of the major forms of a group of conditions called epidermolysis bullosa. Epidermolysis bullosa cause the skin to be very fragile and to blister easily. Blisters and skin erosions form in response to minor injury or friction, such as rubbing or scratching. The signs and symptoms of dystrophic epidermolysis bullosa vary widely among affected individuals. In mild cases, blistering may primarily affect the hands, feet, knees, and elbows. Severe cases of this condition involve widespread blistering that can lead to vision loss, scarring, and other serious medical problems.

Clinical Implications of Subcategorizing BI-RADS 4 Breast Lesions associated with Microcalcification: A Radiology–Pathology Correlation Study

Abstract:  Currently radiologists have the option of subcategorizing BI‐RADS 4 breast lesions into 4A (low suspicion for malignancy), 4B (intermediate suspicion of malignancy), and 4C (moderate concern, but not classic for malignancy). To determine the clinical significance of BI‐RADS 4 subcategories and the common pathologic changes associated with these mammographic lesions, a retrospective review of 239 consecutive stereotactic‐needle core biopsies (SNCB) for microcalcifications was performed. All 239 SNCBs were BI‐RADS 4 lesions, and of these, 191 were subcategorized to 4A, 4B or 4C. Ninety‐four of 191 (49%) were 4A, 73 (38%) were 4B, and 24 (13%) were 4C. Fibrocystic change was the most common finding (66/239; 28%) followed by ductal carcinoma in situ (DCIS) accounting for 23% of cases. This was followed by columnar cell alteration with or without atypia (47/239; 19%), and fibroadenoma (45/239; 19%). While 70% (17/24) of BI‐RADS 4C category lesions were DCIS, only 21% (15/73) of BI‐RADS 4B and 10% (10/94) of BI‐RADS 4A were DCIS. Without sub‐categorization, carcinoma was diagnosed in 23% (55/239) of all cases with BI‐RADS 4. Therefore, subcategorizing BI‐RADS 4 lesions is important since it not only benefits the patient and clinician in understanding the level of concern for carcinoma, but will also alert the pathologist.

Factors determining adequacy of axillary node dissection in breast cancer patients

Abstract:  With increased focus on quality assurance, a complete axillary lymph node dissection (ALND) has been defined as the removal of 10 or more lymph nodes (LN). The objective of this study was to determine which patient, physician, and geographic factors predict the adequacy of ALND in breast cancer patients. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a multicenter, prospective study of 4,131 patients, all of whom had a sentinel node biopsy and completion ALND. Univariate and multivariate analyses were performed to determine which factors were independently associated with the removal of 10 or more LN. Of the 4,131 patients in this study, the median number of LN removed was 11 (range; 3–45). Ten or more LN were removed in 3,213 (77.8%) patients. The median patient age in this study was 60 (range; 27–100), with a median tumor size of 1.5 cm (range; 0.1–11.0 cm). On univariate analysis, patient age, tumor size, and palpability were correlated with adequacy of ALND. Academic affiliation and percentage of breast practice were significant physician factors predictive of adequacy of ALND. Both geographic region and community size were significantly correlated with adequacy of ALND. On multivariate analysis, patient age (p = 0.024), surgeon academic affiliation (p < 0.001), percentage breast practice (p < 0.001), and community size (p = 0.003) were significant determinants of adequacy of ALND. Younger patients were more likely to have an adequate ALND. Surgeons in academic practice had a higher rate of adequate ALND, as did those practicing in larger communities. Surgeons with a more breast experience had a lower rate of adequate ALND. Patient age, surgeon academic affiliation, and breast experience, as well as community size are all significant factors predictive of adequacy of ALND.

Rosai-Dorfman Disease of the Gastrointestinal Tract: Report of a Case and Review of the Literature

Rosai-Dorfman disease (RDD) is a rare, acquired disease of unknown etiology that affects primarily children and young adults. It is characterized by a proliferation of distinctive histiocytes in the lymph nodes and/or extranodal sites. Involvement of the gastrointestinal tract is rare. We report a case of RDD in a 60-year-old woman who presented with hematochezia and was found to have RDD of the rectum presenting as a rectal mass. This report highlights the current pathogenetic mechanisms, immunohistochemical markers, and the gastrointestinal manifestations of RDD.

Altered Expression of α-Methylacyl-Coenzyme A Racemase in Prostatic Adenocarcinoma Following Hormone Therapy

alpha-Methylacyl-coenzyme A racemase (AMACR) is a sensitive and specific tissue marker for the diagnosis of prostatic carcinoma. However, limited data are available on AMACR expression in residual prostatic carcinoma following hormone therapy. We analyzed 64 residual or recurrent prostatic adenocarcinomas following hormonal therapy for the expression of AMACR using a monoclonal antibody (P504S) to AMACR. In 20 localized cases, AMACR staining was absent in 11 (55%), 1+ in 6 (30%), and 2+ or 3+ in 3 (15%). However, in 15 metastatic cases, AMACR was absent in 1 (7%), 1+ in 3 (20%), and 2+ or 3+ in 11 (73%). None of the 29 postradiotherapy cases showed complete absence of AMACR staining: 2 (7%) were 1+, and 27 (93%) were 2+ or 3+. AMACR expression was reduced significantly in the majority of posthormonal residual carcinomas, whereas in postradiotherapy and in hormone-refractory metastatic prostatic adenocarcinoma, AMACR expression was retained. Therefore, the diagnosis of residual prostatic carcinoma after hormonal therapy using AMACR immunostaining must be interpreted with caution. Furthermore, AMACR might have a role in the recurrence of prostatic adenocarcinoma after medical therapy.

Bilateral carotid body tumor: The role of fine-needle aspiration biopsy in the preoperative diagnosis

Carotid body (CB) is a round to ovoid or flattened structure situated within the adventitia of the common carotid artery bifurcation on both sides of the neck. CB contains two basic types of cells: chief cells (or glomus type 1) and sustentacular cells (glomus type 2). Carotid body tumor (CBT) or paraganglioma arises from the chief cells of the carotid body. The diagnosis of CBT is typically made with radiological studies. Fine needle aspiration biopsy (FNAB) is seldom requested for this purpose due to rare but dreadful reported complications such as hemorrhage and damage to the carotid artery. In this report we discuss the cytological findings of a malignant CBT diagnosed by FNAB in a 22 year‐old female. Diagn. Cytopathol. 2008;36:178–180.