Joseph F. Nasuti

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.

Fibrillin and other matrix proteins in mitral valve prolapse syndrome

BACKGROUND Unlike myxomatous degeneration in Marfan syndrome, which has been reported to result from a mutation in the gene that codes for the extracellular structural protein fibrillin, no specific molecular abnormality has been documented to be the underlying cause of myxomatous degeneration in mitral valve prolapse syndrome (MVPS). The present study examined the distribution of fibrillin and other extracellular matrix proteins in patients with isolated MVPS. METHODS Mitral valve leaflets from 7 MVPS patients and 5 rheumatic heart disease (RHD) patients were characterized immunohistochemically for fibrillin, elastin, collagen I, and collagen III distribution, and compared with five normal mitral valves. RESULTS In normal mitral valve leaflets immunostaining for fibrillin, elastin, collagen I, and collagen III revealed a fibrillary and laminar pattern in the atrialis and the spongiosa. In addition, both the collagens were present in the ventricularis, and the coarse bundles in the fibrosa exhibited alternating bandlike collagen I immunoreactivity. The staining patterns of fibrillin, elastin, and collagens I and III revealed distinctly different distribution in MVPS relative to the normal and RHD leaflets. MVPS leaflets in areas of myxoid degeneration displayed a more diffuse, weaker, and nonlaminar pattern of staining for fibrillin. Similar, but less severe abnormality of elastin, collagen I, and collagen III was also observed. Unlike diffuse abnormality in MVPS, the disruption of extracellular proteins in RHD only occurred at the site of the inflammatory damage, but the overall architecture was preserved. CONCLUSIONS The results of the current study suggest a primary role for abnormal fibrillin and other matrix proteins in producing myxoid degeneration of mitral valve leaflets in MVPS.

Nontyrosine crystalloids in salivary gland lesions: Report of seven cases with fine-needle aspiration cytology and follow-up surgical pathology

We report a series of seven patients who underwent fine‐needle aspiration (FNA) for clinically apparent parotid gland lesions. In all seven cases, numerous to abundant polyhedral, multifaceted (nontyrosine) crystalloids were noted in the background of scanty cellular specimens composed predominantly of oncocytic cells. Subsequent surgical excision showed that three of the seven glands revealed sialolithiasis and sialadenitis without evidence of neoplasia. The histology of the remaining four cases consisted of two Warthins tumor, one oncocytic papillary cystadenoma, and one cellular benign mixed tumor. In all seven cases the nontyrosine crystalloids were found in highest concentrations in cystic spaces lined with oncocytic metaplastic cells. We conclude that nontyrosine cystalloids can be associated with both neoplastic and nonneoplastic salivary gland disease, and they may be a product of oncocytic cell secretion. Diagn. Cytopathol. 2000;22:167–171.

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.

Significance of Tissue Fragments in Voided Urine Specimens

OBJECTIVE To determine the diagnostic significance of tissue fragments in voided urine specimens. STUDY DESIGN We reviewed all the voided urine specimens collected and processed by the Millipore filter technique (Bedford, Massachusetts, U.S.A.) at our institution between January 1, 1997, and December 31, 1998, and the corresponding biopsies obtained within 120 days after urine examination. The type and number of tissue fragments were correlated with the histologic diagnosis and clinical features; the results were compared to those from a recently published study. RESULTS Of the 2,553 voided urine specimens examined, 174 (7%) had corresponding biopsies. Cell groups (tissue fragments) consisting of either flat sheets or three-dimensional structures were significantly more common (57%) (chi 2 P < .005) in urine specimens with biopsies revealing urothelial malignancies than in negative biopsies (6%). Three-dimensional groups were also statistically more common in cases with invasive transitional cell carcinoma. Proper identification of tissue fragments was highly significant and correlated with urothelial neoplastic changes. CONCLUSION The results of the present investigation using the Millipore filter technique for voided urine cytology processing, differed from those of a recently published study that employed cytocentrifugation. Tissue fragments, to be differentiated from groups, clumps or clusters that often result from centrifugation and other concentration artifacts, were strongly associated with urothelial neoplasia, uncommonly with nonneoplastic disease processes affecting the urinary tract but always with urothelial disease.

Value of Mucin Detection in Distinguishing Mucoepidermoid Carcinoma from Warthin’s Tumor on Fine Needle Aspiration

OBJECTIVE To examine the validity of the presence of mucin, utilizing a semiquantitative, statistical approach, as a criterion for distinguishing low to intermediate grade mucoepidermoid carcinoma (ME) from Warthins tumor (WT). STUDY DESIGN We selected histologically established fine needle aspiration (FNA) cases of ME (26) and WT (30) from a six-year period (January 1995-January 2001). Mucicarmine staining was performed on the FNA preparations. The amount of mucin detected was rated on a scale of 1-3, as follows: 1 = no mucin present, 2 = mucin present in the background and < 5% of tumor cells, and 3 = mucin present in the background and > or = 5% tumor cells. The scores for the 30 WTs and 26 MEs were tabulated and analyzed for statistical significance utilizing the Student t test. RESULTS The mean mucin score for the 26 MEs was 1.81, SD .63. The mean mucin score for the 30 WTs was 1.52, SD .74. There was no statistically significant difference (P = .122) in the amount of mucin present between MEs and WTs in the 56 aspirate specimens examined. CONCLUSION Based on the results of this study, the presence of extracellular or intracellular mucin in FNA specimens of salivary gland tumors may not be a reliable criterion for distinguishing WT from ME.

Value of histiocyte detection in Pap smears for predicting endometrial pathology: An Institutional Experience

OBJECTIVE To determine the clinical implications of the finding of histiocytes in Pap smears in 1 patient population. STUDY DESIGN The medical records and Pap smears which the presence of histiocytes was mentioned in the diagnosis between August 1996 and August 2001 were reviewed in conjunction with follow-up surgical findings. The positive predictive value (PPV) for significant endometrial pathology for the isolated finding of histiocytes on Pap smear was determined. RESULTS Of the 238,225 women screened over a 60-month period, 325 were reported to have histiocytes in their Pap smears. Of them, 238 (73.2%) had subsequent endometrial sampling, hysterectomy or both, and follow-up Pap smears. Two hundred seven smears (87%) failed to disclose endometrial pathology. Thirty-one cases (13%) resulted in significant histopathologic findings, including 12 uterine malignancies, 8 endocervical polyps, 7 endometrial polyps, 2 submucosal leiomyomata, 1 simple hyperplasia without atypia and 1 case of tamoxifen-related changes. Upon review of the clinical records, 58% (18/31) of those patients had other significant clinical and/or cytologic findings. Five of the 18 patients (27.8%) had associated postmenopausal bleeding, 11 had additional abnormal Pap smear findings (atypical glandular cells, 6/18, or 33.3%; endometrial cells, 5/18, or 27.8%), and another 2 had both postmenopausal bleeding and atypical glandular cells (2/18, or 11.1%). The PPV for significant uterine pathology for women with the isolated finding of histiocytes on a Pap smear was 5.5% and 60% with additional clinical and/or Pap smear findings. The PPV for endometrial cancer was 1.3% in women with the isolated finding of histiocytes on a Pap smear but 20% for women with histiocytes and additional clinical/or Pap smear findings. CONCLUSION Based on the findings of this study and recently published data, we conclude that the isolated finding of increased histiocytes in the absence of postmenopausal bleeding, endometrial cells or atypical glandular cells on a Pap smear is a poor indicator of uterine disease.

Differential Immunocytochemical Staining Patterns of Uroplakin Observed on Neoplastic and Nonneoplastic Tissue Fragments Obtained from Upper Urinary Tract Brush Specimens

OBJECTIVE To discern any differences in the distribution of uroplakin expression on neoplastic and nonneoplastic upper urinary tract lesions. STUDY DESIGN Thirty-seven representative 95% ethanol-fixed direct smears of brush specimens, which were subsequently diagnosed histologically as 10 reactive and 27 transitional cell carcinomas (TCCs), were stained with polyclonal uroplakin antibodies utilizing the avidin-biotin-peroxidase method. In order to ascertain any differences in diagnostic accuracy between conventional cytomorphology and uroplakin immunocytochemical staining, the results were compared to the original final cytologic diagnoses for all 37 cases. RESULTS The linear staining pattern on the luminal surface of umbrella cells was the dominant pattern expressed on tissue fragments from all 10 reactive lesions. Tissue fragments from low grade TCC demonstrated a weaker and less continuous superficial membrane staining pattern along with a variably intense, diffuse, membranous staining pattern throughout the tumor cell groups. This staining pattern was seen in all 17 (sensitivity = 100%) histologically confirmed low grade TCCs, of which only 13 of the 17 (sensitivity = 76.5%) were diagnosed as TCC on the original final cytology report. Tissue fragments from 10 high grade TCCs lacked the superficial linear staining pattern seen in reactive cell groups. Instead, all 10 high grade TCCs displayed a strong diffuse membrane staining pattern in all the cells in the fragment and also demonstrated microluminal structures within the tumor cell groups. CONCLUSION The distinctive patterns of uroplakin antigen expression observed in nonneoplastic and neoplastic upper urinary tract lesions in the present study can greatly enhance the accuracy of diagnostic interpretation of upper urinary tract lesions in conventional cytologic specimens.

Semiquantitative analysis of the cellular preservation quality of Normosol® and Carbowax® solutions for thyroid fine-needle aspiration specimens

The present study was designed to compare cytomorphologic features and diagnostic value of thyroid fine‐needle aspiration (FNA) specimens stored in Saccomanos (Carbowax® solution) fixative and Normosol® solutions. Equivalent amounts of aspirate material obtained from nonlesional areas of 17 freshly resected thyroidectomy specimens were placed in room temperature Carbowax® solution and refrigerated Normosol® solution for a time period of up to 60 hr. Millipore® filter preparations were made from both fluids for each of the 17 thyroidectomy specimens. Slides were examined by three independent observers who rated the quality of cellular preservation based on a four‐part semiquantitative scale. Statistical analysis of the data obtained from the scores of the three observers showed no statistically significant difference in the quality of specimen preservation. Normosol® preserved specimens consistently rated superior to Carbowax® in nuclear detail, lack of obscuring background artifact, and diagnostic value. These findings, along with a considerably less cost, make refrigerated Normosol® an attractive alternative for the short‐term storage of FNA specimens placed in fluid. Diagn. Cytopathol. 2000;22:319–322.