Kamal K. Khurana

Diagnosing Primary and Metastatic Renal Cell Carcinoma: The Use of the Monoclonal Antibody `renal Cell Carcinoma Marker'

The diagnosis of primary or metastatic renal cell carcinoma (RCC) can be difficult, especially in small biopsies, because of the wide variety of histologic appearances and clinical presentations that RCC can assume. An immunomarker specific for RCC is currently not available. We tested the relevant diagnostic use of the Renal Cell Carcinoma Marker (RCC Ma), a monoclonal antibody, against a normal human proximal tubular brush border antigen. Immunostaining using RCC Ma and the avidin-biotin-peroxidase complex technique was performed on archival tissues from primary and metastatic tumors of renal or nonrenal origin. A total of 122 of 153 primary RCCs (79.7%) were positive [clear cell (84%), papillary (96%), chromophobe (45%), sarcomatoid (25%), and collecting duct (0%)], with ≥10% of tumor cells stained in 93% of cases. None of the 64 primary renal tumors other than RCC, including 15 oncocytomas, was positive. Fifteen of 146 (10.2%) nonrenal primary tumors were positive (5 of 17 breast tumors, 8 of 8 parathyroid adenomas, and 2 of 7 embryonal carcinomas). Forty-two of 63 (67%) metastatic RCCs were positive with ≥10% of cells being stained in 83% of them. Two of 108 (2%) metastases from tumors other than RCCs were positive, both of which were metastatic breast carcinomas; however, only 10% (2 of 19) of metastatic breast carcinomas were positive. RCC Ma is an excellent marker for primary RCC, which should facilitate its diagnosis in a small biopsy. Although RCC Ma remains highly specific (98%) for metastatic RCC, a negative result may not rule out metastatic RCC because of a rather low sensitivity and a focal staining pattern in some of the positive cases. RCC Ma may also facilitate the differential diagnosis between oncocytoma and other types of RCC when they are composed mostly of eosinophilic cells.

Comparison of palpation-guided versus ultrasound-guided fine-needle aspiration biopsies of thyroid nodules in an outpatient endocrinology practice.

OBJECTIVE To investigate the role of thyroid ultrasonography in our outpatient endocrine practice. METHODS We compared the efficacy of ultrasound-guided fine-needle aspiration biopsy (US-FNAB) of thyroid nodules with that of palpation-guided aspiration (P-FNAB) and determined the malignancy rates of palpable and nonpalpable nodules. All patients referred for assessment of thyroid nodular disease from October 1997 through August 2001 were included in the study. Fine-needle aspirations were performed by palpation guidance until October 1999, after which US-FNAB was exclusively performed. All thyroid examinations, ultrasound imaging, and aspiration biopsies were performed by the same endocrinologist in an office-based setting. Histopathologic and cytologic diagnoses were compared for patients who underwent thyroidectomy. RESULTS A total of 376 nodules in 276 patients were aspirated during a 47-month period. P-FNAB was used on 157 nodules, and US-FNAB was performed on 219 nodules (both procedures were done on 21 nodules). For palpable thyroid nodules that were resected, the cytologic diagnostic accuracy rate was 60.9% and 80% for P-FNAB and US-FNAB, respectively. With use of ultrasound guidance, the sensitivity, positive predictive value, and negative predictive value increased significantly. In addition, the inadequate specimen rate decreased from 11.2% in the P-FNAB group to 7.1% in the US-FNAB group. Among the nodules that were not palpable, the malignancy rate was similar to that for the palpable thyroid nodules (5.1% versus 6.8%). CONCLUSION US-FNAB improved the cytologic diagnostic accuracy, sensitivity, and positive predictive value and reduced the false-negative rate in comparison with P-FNAB. The malignancy rate for nonpalpable thyroid nodules was similar to that for palpable nodules.

Parathyroid cytology: Avoiding diagnostic pitfalls

Interpretation of parathyroid fine‐needle aspirates (FNA) remains problematic not only because this type of specimen is rare but also because the pertinent literature is very limited. We systematically reviewed parathyroid FNAs in our files and sought to delineate additional diagnostic criteria.

Diagnostic Pitfalls of Aspiration Cytology of Salivary Duct Carcinoma

Salivary duct carcinoma (SDC) is a highly aggressive primary salivary gland neoplasm that resembles intraductal and infiltrating breast carcinoma histologically. The purpose of this study was to review the cytologic features of histologically proven salivary duct carcinomas and to identify the potential pitfalls in cytologic diagnosis.

Cytokeratin 19 Immunolocalization in Cell Block Preparation of Thyroid Aspirates An Adjunct to Fine-Needle Aspiration Diagnosis of Papillary Thyroid Carcinoma

CONTEXT Immunohistochemical staining for cytokeratin 19 (CK-19) is a useful ancillary technique for diagnosing papillary thyroid carcinoma (papillary carcinoma) in histologic specimens. Although similar results have been obtained on aspirate smears, to our knowledge the utility of CK-19 immunolocalization in cell block preparations as an adjunct to fine-needle aspiration diagnosis of papillary carcinoma has not been examined. OBJECTIVE The purpose of this study was to determine whether CK-19 immunostaining of cell block preparations of thyroid aspirates is a useful ancillary technique for diagnosing papillary carcinoma. MATERIALS AND METHODS Using a monoclonal antibody to CK-19 and a standard avidin-biotin complex technique, immunostaining was performed on paraffin-embedded cell blocks of 57 cases with the following cytologic diagnoses: (a) papillary carcinoma (20 cases); (b) atypical cytology, cannot exclude papillary carcinoma (19 cases); and (c) nonneoplastic thyroid (18 cases). The staining reaction in each case was graded on the basis of percentage of epithelial cells stained (1+, <10%; 2+, <10%-50%; 3+, >50). Tissue follow-up was available in all cases. RESULTS Nineteen (95%) of 20 cases with an unequivocal diagnosis of papillary carcinoma were positive for CK-19 (3+). Tissue follow-up confirmed papillary carcinoma in all 20 cases. Of the 19 cases with a diagnosis of atypical cytology, cannot exclude papillary carcinoma, 7 (37%) cases displayed 3+ immunostaining and subsequent excision confirmed papillary carcinoma in all 7 cases. The remaining 12 cases with 1+ immunostaining included surgically confirmed goiter (6 cases), adenoma (2 cases), lymphocytic thyroiditis (3 cases), and papillary carcinoma (1 case). The follicular cells in 18 cases with a cytologic diagnosis of nonneoplastic thyroid showed 1+ immunostaining. Histologic follow-up of these cases confirmed the nonneoplastic cytologic diagnoses. CONCLUSIONS Cytokeratin 19 immunostaining of cell block preparations of thyroid aspirates serves as a useful tool for the diagnosis of papillary carcinoma. Strong immunostaining (3+) for CK-19 aids in accurate diagnosis of malignancy in cytomorphologically equivocal cases of papillary carcinoma.

Prophylactic mastectomy: pathologic findings in high-risk patients.

BACKGROUND According to recently published data, prophylactic mastectomy (PM) appears to prevent about 90% of the expected malignant neoplasms in women with a family history of breast cancer. OBJECTIVES To identify the frequency of high-risk lesions in PM specimens and to determine occurrence of any new primary breast cancer following PM. DESIGN We performed a retrospective study of women undergoing unilateral or bilateral PM. Medical charts and pathologic findings of 35 patients who underwent bilateral mastectomies at University Hospital, Syracuse, NY, from 1989 to 1996 were reviewed. Patients with biopsy-proven bilateral breast cancer were excluded. Patients were divided into 3 groups: (A) positive family history and no known breast cancer (n = 9), (B) positive family history and contralateral neoplasia (n = 13), and (C) negative family history and contralateral neoplasia (n = 13). These findings were compared with those found in reduction mammoplasty specimens from 10 women at standard risk of breast cancer. RESULTS The mean age of the control group of women undergoing reduction mammoplasty was 38 years. The pathologic specimens demonstrated no significant pathologic findings in 9 and fibrocystic change in 1. In group A, the mean number of affected relatives was 3.1, and the mean age was 38 years. Two of these 9 women had atypical duct hyperplasia and 1 had atypical lobular hyperplasia in their breasts (ie, 33% with high-risk pathologic findings). Of the 13 group B women (mean age, 46.6 years; mean of 2.5 affected relatives and unilateral breast cancer), the contralateral PM specimen contained duct carcinoma in situ in one and invasive ductal cancer in a second (15% with occult malignant neoplasms). In 13 group C patients (mean age, 47.1 years), 3 (23.1%) of the contralateral PM specimens displayed atypical duct hyperplasia or atypical lobular hyperplasia. At a mean follow-up of 4.8 years, there have been no new breast malignant neoplasms in these 45 women. CONCLUSIONS The occurrence of unilateral cancer in patients with family history of breast cancer is associated with a 15.4% probability of simultaneous occult malignant neoplasms in the contralateral breast. Patients with a strong family history but no evidence of breast cancer have a substantially similar rate of proliferative disease in their PM specimens as those women who have unilateral cancer but no significant family history.

Diagnostic Utility of Intracytoplasmic Lumen and Transgressing Vessels in Evaluation of Hurthle Cell Lesions by Fine-Needle Aspiration

INTRODUCTION Recent abstracts have emphasized the importance of recognizing intracytoplasmic lumen and transgressing vessels as useful criteria enabling distinction between Hürthle cells encountered in neoplastic and nonneoplastic thyroid aspirates. The purpose of this retrospective study was to evaluate if application of these criteria improves specificity and sensitivity of cytologic diagnosis of true Hürthle cell neoplasms. MATERIALS AND METHODS We retrospectively reviewed 30 fine-needle aspirates of thyroid with cytologic diagnosis of Hürthle cell neoplasms (13 cases) and nonneoplastic thyroid with prominent Hürthle cells (17 cases). All cases were evaluated for the presence of intracytoplasmic lumen and transgressing vessels and were reclassified as neoplastic or nonneoplastic based on the presence or absence of 1 or both of these criteria. Surgical follow-up was available in all cases. RESULTS Surgical follow-up in 13 cases of Hürthle cell neoplasms revealed Hürthle cell carcinoma (3 cases), Hürthle cell adenoma (6 cases), and Hashimotos thyroiditis (4 cases). Seventeen cases with nonneoplastic diagnosis revealed Hürthle cell carcinoma (1 case), Hashimotos thyroiditis (12 cases), and nodular goiter (4 cases). After application of the previously mentioned cytologic criteria, the cytologic diagnoses were reclassified as Hürthle cell neoplasms (13 cases) and nonneoplastic thyroid (17 cases). The true sensitivity of the test before and after the application of the criteria was 90% and 100%, respectively. The true specificity before and after the application of the cytologic criteria was 65% and 85%, respectively. CONCLUSIONS Intracytoplasmic lumen and transgressing vessels are helpful features in distinguishing neoplastic and nonneoplastic Hürthle cell thyroid lesions. Use of these criteria may improve the specificity and sensitivity of the cytologic diagnosis.

Fine needle aspiration cytology of invasive micropapillary carcinoma of the breast : A report of two cases

BACKGROUND Invasive micropapillary carcinoma is a recently described variant of invasive breast cancer characterized by the formation of micropapillae within clear spaces separated by a fibrocollagenous stroma. Although the histologic features are well described, to the best of our knowledge, the cytologic findings have not been reported. CASES The fine needle aspiration cytology of two cases of biopsy confirmed invasive micropapillary carcinoma are described and compared to the histologic features. In one case, an additional FNA of a subsequent metastasis is reviewed. CONCLUSION The cytologic features of invasive micropapillary carcinoma are distinctive and correlate with the histology. Invasive micropapillary carcinoma can be suggested based on the FNA findings of numerous well-formed angular, papillary clusters along with other criteria of malignancy. The cytologic differential diagnosis of invasive micropapillary carcinoma is discussed.

Aspiration cytology of malignant neoplasms associated with granulomas and granuloma‐like features

Malignant lymphomas and solid tumors that mimic or are associated with epithelioid granulomas are widely recognized in surgical pathology, but have received little attention in the cytopathology literature. In this study the authors present their experience with six such cases in which the presence of granulomas or granuloma‐like features posed a diagnostic difficulty on fine‐needle aspiration cytology (FNAC).

Is c‐kit (CD117) immunolocalization in cell block preparations useful in the differentiation of adenoid cystic carcinoma from pleomorphic adenoma?

Recent studies in the surgical pathology literature have revealed that overexpression of the tyrosine kinase receptor protein c-kit (CD117) occurs in adenoid cystic carcinoma, suggesting that c-kit may be useful as an ancillary marker for this tumor. This marker would be particularly useful in small biopsies and in cell block preparations of fine-needle aspiration biopsy (FNAB) material, in which differentiation between adenoid cystic carcinoma and pleomorphic adenoma can be challenging and carries important therapeutic implications. We evaluated the role of c-kit antigen expression in cell block material obtained during FNAB in distinguishing between adenoid cystic carcinoma and pleomorphic adenoma. Formalin-fixed, paraffin-embedded cell block sections of pleomorphic adenoma specimens from the parotid (n 13) and submandibular glands (n 2), as well as adenoid cystic carcinoma specimens from the palate (n 3), maxilla (n 2), buccal mucosa (n 2), tongue (n 1), parotid (n 1), and ethmoid sinus (n 1), were selected from the archival pathology files of the State University of New York–Upstate Medical University (Syracuse, NY). All patients had subsequently undergone surgical excision, and the corresponding tissue analysis confirmed the FNAB diagnosis in all cases. Immunohistochemical studies were performed on formalin-fixed, paraffinembedded tissue sections measuring 4 m in thickness using a modified avidin-biotin-peroxidase complex detection method. Two antibodies were used to detect c-kit expression: H300, a polyclonal antibody against the amino terminus of human c-kit (1:65 dilution; Santa Cruz Biotechnology, Santa Cruz, CA), and A4502, a polyclonal 207 CANCER CYTOPATHOLOGY