Daniel Sudilovsky

HER2 Protein Expression and Gene Amplification in Androgen-Independent Prostate Cancer

The role of the HER2 receptor remains uncertain in the pathogenesis and progression of human prostate cancer. Previous studies have reported widely divergent rates for HER2 expression in primary prostate tumors, probably owing to significant methodologic differences in the studies. Few data exist about the frequency of HER2 protein overexpression and gene amplification in androgen-independent prostate cancer (AIPC), although recent xenograft models suggest HER2 expression may be up-regulated in the transition from androgen-dependent to androgen-independent disease. We studied the role of HER2 protein in AIPC by immunohistochemical and fluorescence in situ hybridization (FISH) analyses on AIPC specimens using well-characterized and validated reagents. Fourteen (36%) of 39 specimens expressed HER2; however, only 2 (5%) had moderate (2+) expression, and 2 (5%) had high-level (3+) expression. Two (6%) of 36 specimens had gene amplification by FISH. These data suggest that HER2 protein overexpression and gene amplification are relatively uncommon in AIPC.

Utility of intraoperative frozen section analysis of surgical margins in region of neurovascular bundles at radical prostatectomy.

OBJECTIVES To report our experience with intraoperative frozen section (IFS) analysis in patients who are potential candidates for nerve-sparing surgery. Potency can be maintained in select patients who undergo radical prostatectomy using a nerve-sparing approach. However, extracapsular disease extension in the area of the neurovascular bundles may compromise adequate surgical margins in some patients undergoing such surgery. METHODS We reviewed the pathologic results from 101 patients who underwent either unilateral or bilateral nerve-sparing radical prostatectomy in whom IFS analysis was performed. The clinical disease stage was T1 in 20 patients and T2 in 81 patients. The mean serum prostate-specific antigen level before surgery was 7.2 ng/mL. Of the 101 patients, 62, 28, and 11 had a biopsy Gleason score of 2 to 6, 7, and 8 to 10, respectively. IFS analysis was performed on the surgical margin thought to be at risk of tumor involvement as determined by the results of systematic prostate biopsy, transrectal ultrasonography, or intraoperative inspection. If the frozen section was positive, additional tissue, including the neurovascular bundle, was subsequently removed to establish clear surgical margins. IFS results were compared with those on the final, permanent tissue section, as well as with the status of the additionally resected tissue. RESULTS The IFS results were identical to those obtained on the final, permanent section in 92 (91%) of the 101 cases. The IFS results showed positive margins in 15 (15%) of 101 patients. Of these cases, 11 demonstrated positive margins on the final permanent sections. Of the 86 patients with negative frozen section diagnosis, 5 had positive surgical margins on permanent sections at the site of the IFS. The positive and negative predictive value for the IFS technique was 73% and 94%, respectively. Of the 15 patients with positive IFS, 12 (80%) had no evidence of tumor in the additionally resected tissue. Prostate-specific antigen recurrence was noted in 7% of the study population. The risk of recurrence in patients with either positive or negative IFS findings was similar. CONCLUSIONS IFS at the time of radical prostatectomy can reliably predict the final surgical margin status in most carefully selected high-risk patients when there are concerns about the margin status.

Docetaxel, estramustine, plus trastuzumab in patients with metastatic androgen-independent prostate cancer

The incidence of human epidermal growth factor receptor 2 (HER2) protein overexpression and its prognostic value are not well characterized in patients with prostate cancer. A phase I study was designed to evaluate docetaxel/estramustine plus trastuzumab, a humanized monoclonal antibody that binds to the HER2 receptor, in patients with metastatic androgen-independent prostate cancer (AIPC). HER2 positivity was not required because safety was the primary endpoint. Patients received oral estramustine 280 mg three times daily (days 1 to 5); docetaxel, 70 mg/m(2) intravenously (day 2); and trastuzumab, 2 mg/kg intravenously (days 2, 9, and 19), every 21 days until the disease progressed or toxicity became unacceptable. This regimen was well tolerated among the first 13 treated patients. Grade 4 neutropenia was seen in 10% of administered cycles. There were two episodes of febrile neutropenia and two thrombembolic events. Of the 13 patients evaluable for prostate-specific antigen (PSA) response, nine (69%) experienced a decrease in PSA level of >50%. Two (33%) of six patients with measurable disease had objective responses, and one complete response was seen on bone scan. Docetaxel/estramustine/trastuzumab appears to be a safe combination when used in the treatment of metastatic AIPC. The response data are too preliminary for speculation about the relative benefits of this 3-drug regimen compared with the combination of only docetaxel and estramustine in this clinical setting.

Fine Needle Aspiration Cytology of Dermatopathic Lymphadenitis

OBJECTIVE Dermatopathic lymphadenitis (DL) can be a nonneoplastic cause of an enlarged lymph node or nodes. Cytologic findings of DL have not been well described. The differential diagnosis includes Langerhans histiocytosis (LH) in children and low grade lymphoma in adults. We present three cases of dermatopathic lymphadenitis with a discussion of cytologic findings and differential diagnosis. STUDY DESIGN Fine needle aspiration (FNA) findings of three cases of lymph nodes involved by DL were reviewed. All three were axillary lymph nodes in patients with skin rashes. Immunoperoxidase stains for S-100 and CD1a were performed on a cell block from one case, and flow cytometric analysis was performed on another. RESULTS FNA of DL yields cellular smears with abundant histiocytoid cells with moderate cytoplasm and ovoid, vesicular nuclei with longitudinal grooves (interdigitating reticulum cells). These histiocytoid cells are S-100 and CD1a positive. The background cells are mature lymphocytes, scattered eosinophils and plasma cells. Case 1 was originally misinterpreted as consistent with LH. In case 2, flow cytometric analysis of a mixed population of lymphocytes was seen, ruling out lymphoma. In case 3, the diagnosis of DL was based on morphologic features. CONCLUSION Interdigitating reticulum cells in dermatopathic lymphadenitis are S-100 and CD1a positive and could be confused with LH in children. In adults, flow cytometry could be used to distinguish them from low grade lymphoma. FNA findings of DL should be interpreted with the clinical history.

Metastatic balloon cell melanoma : A case report

BACKGROUND The protean morphology of malignant melanoma is diagnostically challenging. Balloon cell melanoma is a histologic variant composed predominantly or entirely of large cells with abundant, vacuolated cytoplasm. It shares the cytologic features of the other subcategories of malignant melanoma, such as discohesion, nuclear pleomorphism and intranuclear cytoplasmic pseudoinclusions, but generally lacks melanin pigment and, as the name would suggest, is characterized by the presence of numerous cytoplasmic vacuoles. CASE A 55-year-old man presented with an enlarged right cervical lymph node. Clinically and radiographically this mass was considered to be metastatic; however, the patient had no known primary neoplasm. Fine needle aspiration biopsy (FNAB) and cytologic examination showed numerous discohesive, variably sized, malignant cells with abundant, vacuolated cytoplasm and pleomorphic nuclei with irregular nuclear contours, macronucleoli and frequent intranuclear cytoplasmic pseudoinclusions. Pigment was not identified. These features, along with strong immunohistochemical positivity for S-100, HMB-45 and Melan-A, suggested the diagnosis of balloon cell melanoma. A right parotidectomy and lymph node dissection were performed, and histologic tissue evaluation confirmed the diagnosis. CONCLUSION This case of lymph node balloon cell melanoma metastasis was diagnosed by FNAB.

Fine needle aspiration cytology of intraoral epithelioid hemangioma. A report of two cases.

BACKGROUND Epithelioid hemangioma (EH) is an uncommon, benign, vascular lesion of unknown etiology. The clinical differential diagnosis is broad and includes both epithelial and vascular neoplasms. In contrast to the histopathology of this lesion, the cytopathology, as obtained by fine needle aspiration biopsy (FNAB), has been described only once before. CASES Two cases of EH of the oral cavity were evaluated by FNAB. The first case included histologic follow-up, while the second included immunohistochemical analysis of the aspirate material (cell block). The smear characteristics included cohesive epithelioid cells with moderate cytoplasm, ovoid nuclei and small nucleoli that formed occasional abortive vascular channels as well as spindle cell groups and a few larger cells with pleomorphic nuclei and irregular nuclear contours against a largely bloody background. Immunohistochemical staining for CD34 and factor VIII-related antigen confirmed the endothelial nature of these proliferations. CONCLUSION The cytomorphology, an endothelial immunophenotype, and the appropriate clinical presentation should permit diagnostic consideration of EH in the differential diagnosis of an endothelial lesion.

Fine needle aspiration cytology of adult perineal rhabdomyosarcoma : A case report

BACKGROUND Adult perineal soft tissue sarcomas are rare. Fewer than 30 cases have been reported, and all were diagnosed after surgical resection by histologic examination. Below we report a case in which the diagnosis was established preoperatively by fine needle aspiration (FNA). CASE A 27-year-old man presented with a firm, midline, perineal mass. Magnetic resonance imaging showed a 3-cm, enhancing mass that was considered neoplastic. FNA biopsy, followed by cytologic examination, revealed moderately cellular aspirates composed of discohesive, small, blue cells with scant cytoplasm, high nuclear/cytoplasmic ratios and pleomorphic nuclei with irregular nuclear contours; uniform, hyperchromatic chromatin; and occasional mitotic figures. Frequent naked nuclei and scattered cells with more abundant, dense cytoplasm and eccentric nuclei were also noted. The diagnosis of rhabdomyosarcoma was favored on FNA and was corroborated by immunohistochemical stains for desmin, myogenin and CD56. Upon surgical resection, the diagnosis of alveolar rhabdomyosarcoma was confirmed histologically and immunophenotypically. CONCLUSION FNA is a useful tool in diagnosing soft tissue lessions of the perineum, including rare primary tumors, such as adult rhabdomyosarcoma. In this case, early identification avoided incisional biopsy and directed appropriate extirpative surgery and reconstruction considerations.

Mucinous adenocarcinoma of the ovary metastatic to the eye: report of a case with diagnosis by fine needle aspiration biopsy.

BACKGROUND Metastatic malignancy involving the ocular uveal tract is rare. Approximately one-third of patients will present without a known primary site. This is the ninth reported clinically detected case of ovarian carcinoma metastatic to the eye, the second with mucinous differentiation and the first in which the diagnosis was established by fine needle aspiration (FNA). CASE A woman developed ovarian mucinous adenocarcinoma metastatic to the choroid layer of the eye. CONCLUSION FNA is useful in diagnosing lesions of the eye and orbit, including diagnosis of rare metastatic lesions.

Intracortical Osteosarcoma A Case Report and Review of the Literature

Intracortical osteosarcoma is the rarest form of osteosarcoma and typically occurs in the young. The authors describe a case of intracortical osteosarcoma arising in the femur of a 44-year-old woman. A diaphyseal location and a typical radiographic appearance, illustrated in this report, distinguish intracortical osteosarcoma from conventional (intramedullary) osteosarcoma, but not from less common forms of osteosarcoma or from several benign bone tumors. This case illustrates the low-grade osteoblastic histology, malignant osteoid formation, and medullary and surrounding soft tissue invasion diagnostic of intracortical osteosarcoma. The authors discuss the diagnostic difficulties presented by intracortical osteosarcoma and the natural history of these tumors. Int.J Surg Pathol 3(3):195-200, 1996