Jean-Marc Cohen

Clinical Significance of Atypical Glandular Cells of Undetermined Significance

OBJECTIVE To determine the rate of atypical glandular cells of undetermined significance (AGUS) and the incidence of subsequent clinically significant lesions. STUDY DESIGN A computer-based search of our cytology laboratory files was performed for cervicovaginal smears diagnosed as AGUS from January 1996 to December 1996. RESULTS In 43,456 cervicovaginal smears examined during the 12-month period, AGUS was reported in 222 (0.5%) cases, with follow-up in 191 (86.0%) (133 [59.9%] biopsies and 58 [26.1%] repeat cervicovaginal smears). Among the patients with repeat cervicovaginal smears, 1 (1.7%) had a high grade squamous intraepithelial lesion, and 10 (17.2%) had persistent AGUS/atypical squamous cells of undetermined significance; the remainder were within normal limits. Thirty-three (24.8%) patients had preneoplastic or neoplastic, squamous or glandular lesions on biopsy (8 [6.0%] cervical intraepithelial neoplasia [CIN] 1, 18 [13.5%] CIN 2/3 and 7 [5.3%] endometrial adenocarcinomas). Half the patients with CIN 2/3 also had evidence of endocervical gland involvement. Squamous lesions were seen more commonly in premenopausal women, while glandular lesions were noted predominantly in postmenopausal women. Patients with a prior abnormal gynecologic history or a concomitant diagnosis of squamous intraepithelial lesion (SIL) had a higher incidence of significant lesions on subsequent biopsy. CONCLUSION Our incidence of AGUS was 0.5%, similar to that in other published reports. AGUS is associated with a significant number of squamous or glandular, premalignant or malignant lesions. A majority of these lesions are high grade SIL, often with endocervical gland involvement. A small but significant number of patients had a glandular malignancy. Our results justify close and persistent follow-up for patients with a diagnosis of AGUS on cervicovaginal smears.

Fine-needle aspiration cytology of spindle cell lesions of the breast

Fine‐needle aspiration biopsy (FNA) has been successful in diagnosing epithelial lesions of the breast. Its role in the evaluation of spindle cell and mesenchymal lesions of the breast, which include a variety of benign and malignant conditions, is less clear. This article discusses the cytologic features and differential diagnosis of these lesions, as well as the potential diagnostic pitfalls associated with them.

Fine-needle aspiration cytology of renal-cell adenocarcinoma metastatic to the breast : A report of three cases

Metastases to the breast from extramammary primary malignancies, including renal adenocarcinoma, are rare. Fine‐needle aspiration biopsy (FNA) is a useful, noninvasive, and rapid procedure to evaluate these mammary lesions. This study describes the cytomorphology of 3 cases of renal‐cell adenocarcinoma metastatic to the breast. All patients had a prior history of renal‐cell adenocarcinoma treated with radical nephrectomy, and they presented with a solitary mammary mass. The cytologic findings showed irregular clusters and dispersed single cells with eccentric nuclei and abundant, vacuolated cytoplasm in a hemorrhagic background. The nuclei were round to oval, with fine granular chromatin and a single, prominent nucleolus. All aspirates were interpreted initially and correctly as consistent with metastatic renal‐cell adenocarcinoma. In summary, a cytologic diagnosis of renal‐cell adenocarcinoma metastatic to the breast can be made by correlating clinical and cytologic findings. The distinction between metastatic extramammary malignancies to the breast and primary mammary carcinoma is critical to avoid unnecessary surgery and to ensure appropriate chemotherapy or radiation therapy. Diagn. Cytopathol. 21:324–327, 1999.

Fine-needle aspiration cytology of desmoplastic malignant melanoma metastatic to the parotid gland : Case report and review of the literature

We report a case of desmoplastic malignant melanoma metastatic to the parotid gland initially evaluated by fine‐needle aspiration. The cytologic findings consisted of scattered spindle cells in a background of heterogeneous lymphoid cells. The spindle cells were scant and displayed mild cytologic atypia. In addition, rare stromal fragments were also present. Cytoplasmic pigment and intranuclear cytoplasmic inclusions were not seen. The initial impression was that of a reactive lymph node with fibrosis. In retrospect, rare spindle cells displayed moderate atypia. In addition, the stromal fragments were cellular and contained spindle cells with mild atypia. These cytologic findings along with a known history of malignant melanoma should provide clues to the correct diagnosis of desmoplastic malignant melanoma. Diagn. Cytopathol. 2000;22:97–100.

Fine-needle aspiration cytology of Rosai-Dorfman disease of the breast: A case report

We report the cytologic findings of a case of Rosai‐Dorfman disease of the breast in a 52‐year‐old diabetic woman, initially sampled by fine‐needle aspiration biopsy (FNA). The patient presented with a 2‐week history of a 3 × 2 cm nodule in the mid–upper area of the left breast. A mammogram taken 6 months prior was negative. FNA smears demonstrated lymphocytes, plasma cells, and large pale cells, with enlarged irregular nuclei, admixed with fragments of fibrous tissue and calcific debris. Lymphophagocytosis (emperipolesis) was scarce. Our diagnosis was atypical lymphohistiocytic proliferation. Flow cytometry was negative, but in the face of a strong clinical suspicion of a lymphoid malignancy, excision was performed. The final diagnosis was Rosai‐Dorfman disease (RDD). The differential diagnosis of FNA of breast inflammatory lesions with atypical cytology is discussed, with a review of the literature. The early recognition on FNA of the hallmarks of this rare disease should prevent unnecessary radical surgery. Diagn. Cytopathol. 1999;21:287–291.

Malignant fibrous histiocytoma, giant cell type, of the breast mimicking metaplastic carcinoma. A case report.

BACKGROUND We report a case of malignant fibrous histiocytoma, giant cell type (MFHGC), of the breast. A review of the literature failed to reveal cytology-based reports on this entity. The cytologic similarity of breast MFHGC on fine needle aspiration biopsy (FNAB) to other malignant breast neoplasms, including carcinoma with osteoclastlike giant cells, metaplastic carcinoma and breast sarcomas, as well as benign reactive processes, makes the recognition of this tumor challenging. CASE A 72-year-old woman presented with a 5-month history of an enlarging breast mass. FNAB of the mass showed a hypercellular smear composed of cohesive, branching clusters of spindle cells with ovoid, focally hyperchromatic nuclei and inconspicuous nucleoli. Interspersed osteoclastlike giant cells, some associated with clusters of spindle cells, were uniformly seen throughout the smear. The background was hemorrhagic, with cellular debris and occasional spindle cells and lymphocytes. No ductal epithelial or myoepithelial cells were seen. An incisional biopsy was performed, followed by radical mastectomy. The histologic examination was diagnostic of MFHGC. The diagnosis was supported by immunohistochemical and electron microscopic studies. CONCLUSION MFHGC, also called primary giant cell tumor of soft tissues, is composed of a mixture of histiocytes, fibroblasts and bland-appearing osteoclastlike giant cells with a multinodular growth pattern. Although MFHGC rarely occurs in the breast and the definitive diagnosis is difficult based on cytology alone, the diagnosis can be considered when a cytologic examination reveals a hypercellular, spindle cell smear with osteoclastlike giant cells in the absence of ductal epithelial or myoepithelial cells.

Fine needle aspiration of primary pleomorphic liposarcoma of the breast. A case report.

BACKGROUND Primary liposarcoma of the breast is an extremely rare lesion. Only two cases describing the aspiration biopsy findings have been reported in the literature. We report the cytologic findings in an additional case, stressing the cytologic clues necessary to distinguish this neoplasm from a primary adenocarcinoma. CASE A 53-year-old female presented to the emergency room with bleeding from a 20-cm, ulcerating mass in the right breast. Four months earlier she had been seen at another institution, where a diagnosis of poorly differentiated carcinoma was made by aspiration biopsy. Computed tomography had been negative for metastatic disease, and the patient refused further evaluation. Aspiration biopsy of the breast mass was repeated at our institution and interpreted as consistent with a poorly differentiated carcinoma. Histologic, immunophenotypic and ultrastructural evaluation of the mastectomy specimen revealed a pleomorphic liposarcoma. CONCLUSION With increasing utilization of fine needle aspiration to evaluate breast lesions, it can be anticipated that unusual entities, including liposarcomas, will be encountered increasingly in breast aspirates. Therefore, it is important to consider liposarcoma in the differential diagnosis of aspirates showing isolated spindle and polygonal cells with vacuolated cytoplasm, nuclear scalloping and pleomorphism to avoid a misdiagnosis of carcinoma.

Prostatic adenocarcinoma metastatic to the breasts: report of a case with diagnosis by fine needle aspiration biopsy.

Metastases of tumors of extramammary origin to the breast are extremely uncommon. We report the case of an 81-year-old man with a history of prostatic adenocarcinoma treated with adjuvant estrogen therapy, who presented with bilateral palpable mammary masses. Mammographic study showed irregular solid nodules. Fine needle aspiration (FNA) biopsy was performed. The aspiration smears showed single cells with high nuclear/cytoplasmic ratios, prominent nucleoli, and rare acinar formations. Immunocytochemical studies using antibodies against prostate-specific antigen and prostate-specific acid phosphatase confirmed the diagnosis of metastatic prostatic adenocarcinoma, allowing appropriate treatment.

Use of computer-assisted rescreening as an ancillary tool to subclassify AGUS cervical smears.

A substantial percentage of women with a diagnosis of atypical glandular cells of undetermined significance (AGUS) on cervical smears harbor a significant squamous or glandular, preneoplastic or neoplastic lesion on subsequent follow‐up. Attempts to subclassify AGUS smears by conventional methods have had mixed results. To determine whether subclassification of AGUS cervical smears using computer‐assisted rescreening based on the neural network would improve correlation with subsequent histologic follow‐up, 91 cervical smears, conventionally diagnosed as AGUS without concomitant squamous lesions, were subjected to analysis by a computer‐assisted automated screening system. Computer‐generated images were evaluated by a cytotechnologist without the knowledge of the histologic outcomes. Prior to manual review, each case was classified as either within normal limits, no review required; or abnormal, review required. Based on the degree of abnormality, the latter category was further subclassified into either low probability or high probability of abnormality. The results of the computer‐assisted reclassification were then compared with the histologic follow‐up of all patients. Thirty‐three cases (38.8%) had a significant lesion on histologic follow‐up. The lesions included 4 CIN I, 7 CIN II/III, 12 endocervical adenocarcinomas (ACA), and 10 endometrial ACA. Based on computer‐generated images, 65% of the smears that were triaged as high probability of abnormality, 11.5% that were triaged as low probability of abnormality, and 10.5% that were triaged as within normal limits had a significant lesion on subsequent follow‐up. We conclude that computer‐assisted rescreening aids in the triage of AGUS smears and that computer‐assisted rescreening based on the neural network or other algorithms may be a useful ancillary tool for subclassifying AGUS cervical smears. Diagn. Cytopathol. 2000;23:165–170.

Peritoneal Cytology in Uterine Papillary Serous Carcinoma

OBJECTIVE To highlight the significance of positive peritoneal cytology in uterine papillary serous carcinoma (UPSC). STUDY DESIGN Seventeen consecutive UPSC cases with peritoneal cytology from 1993 to 1997 were reviewed and compared with the original cytologic diagnosis and extent of tumor involvement in tissues. RESULTS Of the 17 post-menopausal women with UPSC, 11 had early-stage tumors (clinical stage I and II); three cases (27%) with positive peritoneal cytology were upgraded from at least International Federation of Gynecologists and Obstetricians stage IA to IIIA. No change in surgical stage was noted in four of six (67%) advanced cases with positive peritoneal cytology. The review diagnoses of peritoneal cytology did not differ from the original diagnoses. CONCLUSION The features of UPSC in peritoneal cytology are those of a high grade malignancy and may be shared by tumors with similar histology from other sites. The malignant features are readily identified, but the site of origin may not be completely ensured. Positive peritoneal cytology upgrades the surgical stage of early-stage UPSC cases and helps with prognostication and treatment. One case with positive washings but without residual tumor probably represented early spread and/or multicentric origin of the tumor.