Gordon H. Yu

Diagnostic value of lymph node fine needle aspiration cytology: an institutional experience of 387 cases observed over a 5-year period

Lymph node fine needle aspiration (LNFNA) cytology is valuable in solving the diagnostic problems of clinical adenopathy. The usefulness of the procedure in the staging and diagnosis of various malignant and lymphoproliferative tumours, as well as its role in distinguishing reactive hyperplastic lymph nodes from lymphoma, has been documented in the literature generally on an individual basis 1–12 . We report our cumulative 5 year experience of LNFNA representing 387 cases. Approximately half (n = 182) were diagnosed as either metastatic carcinoma or melanoma; in 54 cases (30%) excisional biopsy or tissue study was performed to confirm the diagnosis; there was only one false‐positive diagnosis of a metastatic squamous carcinoma rendered on a submandibular lymph node. Sixty‐one lymphoma cases were successfully diagnosed via LNFNA with no false positives; concurrent flow cytometry was utilized in 51% (n = 31) of the 61 cases and supported the cytologic diagnosis of lymphoma in 27 of the 31 cases (87%). A benign or reactive lymph node process was also diagnosed via LNFNA alone or in combination with flow cytometry in 48 cases with only five false negatives, which included four cases of mantle cell lymphoma and one case of melanoma. Unsatisfactory cases accounted for 12%, and represented specimens obtained by ‘Wang needle’ or other emerging techniques. Our study demonstrates that LNFNA can be an accurate, economical and rapid diagnostic procedure.

Identification of a third component of complement-binding glycoprotein of human platelets.

Utilizing affinity chromatography, a C3-specific binding protein was isolated from 125I surface-labeled human platelets. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated two bands with mean Mr of 64,000 and 53,000, characteristic variability in the relative density of the two bands in a given individual, and the presence of N-linked complex oligosaccharides as well as sialic acid residues not associated with N-linked sugars. These characteristics are similar to those of a human leukocyte iC3- and C3b-binding glycoprotein, termed gp45-70. Further analysis showed that leukocyte gp45-70 and the platelet C3-binding glycoprotein have identical Mr and other similar structural features. Functional characterization of solubilized platelet preparations indicated that gp45-70 has cofactor activity. This membrane glycoprotein is structurally and antigenically distinct from decay accelerating factor (DAF), a complement regulatory protein previously identified on human platelet membranes. DAF and gp45-70 have complementary activity profiles inasmuch as DAF can prevent assembly of and dissociate the C3 convertases but has no cofactor activity, whereas gp45-70 has cofactor activity but no decay accelerating activity. We suggest that these two proteins function conjointly to prevent autologous complement activation.

Difficulties in the fine needle aspiration (FNA) diagnosis of schwannoma

The results of nine FNAs of eight histologically proven schwannomas are presented. In only one of the aspirates was a diagnosis of schwannoma made; three additional cases were diagnosed as ‘spindle cell neoplasm’. Two of the cases were considered to be non‐diagnostic due to hypocellularity, while two cases containing cellular material raised the differential diagnosis of granulation tissue and granulomatous inflammation due to the presence of epithelioid cells and an inflammatory infiltrate, and are illustrated here. The remaining FNA was felt suggestive of branchial cleft cyst due to the presence of only cystic fluid in a neck mass. We observe that: (i) the acquisition of an adequate, representative specimen via FNA is often difficult in schwannoma, and (ii) diagnostic difficulties may be encountered in cases in which cellular material is obtained.

Fine-needle aspiration of cystic parotid gland lesions: An institutional review of 46 cases with histologic correlation

BACKGROUND Many case reports describing various benign and malignant disease entities diagnosed in cystic parotid gland lesions by fine-needle aspiration (FNA) exist in the literature. Very few studies, however, discuss the efficacy and the diagnostic difficulties of FNA cytology in such lesions. The authors report a 5-year institutional experience with FNA cytology of cystic parotid gland lesions and address the accuracy of the procedure and avoidance of diagnostic pitfalls. METHODS A retrospective review of 46 cases in which patients clinically presented with cystic parotid gland lesions was done from a total of 221 parotid FNAs performed over a 5-year period at the University of Pennsylvania Medical Center. The clinical features, cytology, and follow-up surgical pathology were reviewed to determine diagnostic accuracy and highlight potential pitfalls. RESULTS Based on subsequent surgical excision in 29 of the 46 cases of cystic parotid gland lesions, a diagnostic accuracy rate of 83% was obtained for FNA. Approximately 20% (9 of 46 cases) were found to be clinically significant tumors and included 4 mucoepidermoid and 1 adenocarcinoma (NOS), 3 benign mixed tumors, and 1 metastatic melanoma. Three major factors were implicated as diagnostic pitfalls in our series: 1) failure to obtain critical clinical information, 2) overinterpretation of paucicellular specimens, and 3) failure to realize that certain tumors generally perceived as solid masses can present clinically as cystic lesions. CONCLUSIONS FNA cytology is a valuable tool in the primary diagnosis and management of cystic parotid gland lesions. The diagnostic accuracy of this procedure can be significantly improved by acquiring a detailed clinical history, obtaining an adequate cellular specimen, and having knowledge of the variety and frequencies of possible diagnostic entities that may present as cystic parotid gland lesions.

Evaluation of mild‐to‐moderate dysplasia on cervical‐endocervical (Pap) smear: A subgroup of patients who bridge LSIL and HSIL

The Bethesda System recommends Pap smear diagnosis to be based on the most abnormal cells present, regardless of number. Our reporting system includes a diagnostic category of mild‐to‐moderate dysplasia (D1‐2), defined as cases with only a few moderately dysplastic cells. We evaluated the validity of a D1‐2 diagnostic category by reevaluation of 58 cases with subsequent follow‐up (up to 24 months). On biopsy and/or Pap smear follow‐up, 24 cases (41%) showed LSIL and 34 cases (59%) showed HSIL. Index smears from these cases were examined by two cytopathologists blinded to patient follow‐up for the following morphologic features: volumes (scale 1–4) of LSIL, HSIL, and dyskeratosis, HSIL as single cells or syncytial fragments, and acute inflammation. None of the morphologic features evaluated were significantly different between the LSIL and HSIL follow‐up groups based on univariate and multivariate logistic regression analysis. The diagnosis of D1‐2 on Pap smear is a valid diagnostic category that defines a subgroup of patients with both LSIL and HSIL follow‐up, which cannot be reliably predicted based on morphology alone. Diagn. Cytopathol. 2000;23:245–248.

Primary cutaneous osteosarcoma.

A 78-year-old man had a 1-cm cutaneous nodule on his shoulder; subsequent excisional biopsy showed osteosarcoma. There was no connection to deeper structures, and no primary bone lesion was found. The tumor recurred at the same site 9 months after diagnosis and was reexcised. We believe this to be the first well-illustrated case of primary cutaneous osteosarcoma, which should now be included on the list of sarcomas that may occur in the skin.

Papillary formations in metastatic melanoma.

Cytomorphologic features of melanoma can be extremely variable, in that they can mimic other poorly differentiated neoplasms. Ten cases of metastatic melanoma with distinct, cohesive, papillary tissue fragments observed in fine‐needle aspiration (FNA) specimens are reported. These papillary fragments exhibited a central fibrovascular core with attached tumor cells, in a background of single scattered malignant cells, macrophages, and focal necrosis. The aspiration sites included regional or distant palpable lymph nodes, pancreas, bone, and skin. Nine cases had a histologic diagnosis of primary cutaneous melanoma, and in one case the primary skin tumor was detected after the diagnosis was established by FNA of the metastasis. Immunohistochemical studies (S‐100 protein, HMB‐45 antigen, and factor VIII) were performed in four cases, and electron microscopy in one, confirming the diagnosis of melanoma. An awareness of this cytomorphologic variation of papillary formations in cytology preparations from metastatic melanoma is important and can prevent potential inaccurate interpretation. Diagn. Cytopathol. 1999; 20:148–151.

Detection of numerical chromosomal abnormalities by fluorescence in situ hybridization of interphase cell nuclei with chromosome-specific probes on archival cytologic samples

Fluorescence in situ hybridization (FISH) is rapidly emerging as a tool for analyzing numerical and structural chromosomal abnormalities in both liquid and solid tumors. Most studies make use of fresh samples. To determine the feasibility of detecting numerical chromosomal abnormalities (NCA) by FISH using chromosome‐specific probes 8, 12, 17, and X (Vysis, Inc., Downers Grove, IL) on archival cytologic preparations, we studied 23 patient samples, one Papanicolaou‐ and one Diff‐Quik‐stained slide per case (46 slides), and two additional unstained slides (fresh ascitic fluids) as controls. Included in this study were nine ascitic fluids (four benign and five malignant), four malignant pleural fluids, three benign bladder washes, and seven malignant fine‐needle aspirates (FNA) from various sites. The slides ranged from 1–94 days old. After removal of coverslips using xylene, all slides were destained in a series of alcohol and water washes. Pretreatment of slides with pepsin was followed by the in situ hybridization procedure. Two hundred cells per slide were evaluated for distinct separate signals. Results showed the following: 1) all slides were evaluable except for eight (8/46) which had either too few cells or enough cells but with faint signals, 2) the oldest sample showed distinct signals, 3) previously Diff‐Quik‐stained slides showed relatively better signals than Papanicolaou‐stained slides, 4) samples less than a month old showed relatively better signals, and 5) malignant samples showed various NCA, but not the benign samples. We conclude that FISH on archival cytologic preparation 1) is feasible, although age of the slide is a factor since better signals were seen in those less than a month old, 2) shows better results in previously Diff‐Quik‐stained slides, and 3) is a tool that can be used in the retrospective study of various liquid and solid neoplasms. Diagn Cytopathol 1996;14:178–181.

Fine-needle aspiration of pigmented villonodular synovitis of the temporomandibular joint masquerading as a primary parotid gland lesion

The fine‐needle aspiration findings in a case of pigmented villonodular synovitis of the temporomandibular joint are presented. The characteristic cytomorphologic and clinical features of this uncommon, benign fibrohistiocytic lesion are discussed. In addition, due to the initial clinical impression of a primary parotid gland lesion, the differential diagnosis for the cytomorphologic features observed (histiocytoid cells admixed with osteoclast‐like giant cells) are discussed within the context of a primary salivary gland mass. Diagn. Cytopathol., 16:47–50,1997.

Diagnostic significance of signet ring cells in fine-needle aspirates of the breast.

Fine‐needle aspiration (FNA) is a reliable and cost‐effective procedure in the evaluation and management of breast lesions. One diagnostic dilemma that may sometimes arise is the finding of signet ring cells. The isolated finding of such cells in aspirate smears may be particularly problematic in cases of low cellularity or those with otherwise benign features. Although it is generally held that such cells are almost exclusively associated with carcinoma (particularly the lobular subtype), their significance in FNA smears has never been systematically evaluated. To establish their diagnostic utility, we evaluated aspirate smears from 150 cases of histologically proven benign (77) and malignant (73) breast lesions for the presence of signet ring cells, defined as those containing a prominent intracytoplasmic vacuole with nuclear displacement. Signet ring cells were identified in 71% of malignant cases (75% of ductal carcinomas and 71% of lobular carcinomas), mostly as single cells or within small, loosely cohesive tissue fragments. Such cells were also present in 6% of histologically proven benign lesions, most commonly within large tissue fragments. Many of these cells were proven to be vacuolated myoepithelial cells, based on histologic correlation and immunostaining results using anti‐muscle‐specific actin. On the basis of these findings, we conclude that (1) the presence of signet ring cells within small loose tissue fragments or as single cells in FNA smears should prompt close clinical follow‐up (including repeat FNA and perhaps surgical biopsy), regardless of smear cellularity, (2) the presence of signet ring cells in cases of adenocarcinoma does not predict a particular tumor subtype, and (3) rare benign breast lesions may contain signet ring cells, particularly within large tissue fragments, and do not, in isolation, warrant surgical biopsy to exclude malignancy. Diagn. Cytopathol. 16:117–121, 1997.