Hyalinizing clear cell carcinoma: report of eight cases and a review of literature.

Hyalinizing clear cell carcinoma (HCCC) is an extremely rare neoplasm with a female predominance, composed of nests of monomorphic clear cells within a hyaline stroma. This tumor often follows an indolent course and treatment includes wide surgical excision with or without adjuvant radiotherapy. We report eight cases of HCCC identified at two academic institutions in six women and two men, ranging in age from 25 to 86 years. Histologically, all cases demonstrated cords, trabeculae, and nests of monomorphic clear cells as well as cells with eosinophilic granular cytoplasm. Mild cellular atypia was occasionally seen and mitoses were very rare. Seven cases demonstrated a hyalinized stroma, and one case, a myxoid stroma. Immunohistochemically, the tumor cells were positive for epithelial markers and negative for desmin and actin. Seven cases were negative for S-100. Cells were also positive for periodic acid-Schiff and negative for mucin. The important clinicopathologic features and the differential diagnoses of HCCC, as well as a review of the literature are discussed.

Liesegang rings in a submental mass: fine-needle aspiration with histologic correlation.

Liesegang rings are lamellated concretions commonly found in chronic cystic lesions that are inflamed, necrotic, fibrotic, or hemorrhagic. We report on an unusual case of a 14-yr-old girl with an acute, rapidly enlarging solid submental mass in which Liesegang rings were identified on aspirate smears.

The small blue cell dilemma associated with tamoxifen therapy.

CONTEXT: Several endometrial diseases, such as endometrial hyperplasia, endometrial carcinoma, and endometrial polyps, have been reported to be associated with tamoxifen administration. We recently observed a high incidence of distinctive small blue cells in Papanicolaou tests of women who had received tamoxifen treatment for breast carcinoma. OBJECTIVES: To define the characteristics of these small blue cells, to identify the patient population in which they are found, and to determine the clinical significance and possible etiology of these findings. DESIGN: A total of 154 Papanicolaou tests from 60 patients with a clinical history of tamoxifen therapy were reviewed retrospectively. RESULTS: Small blue cells were found in 40% of Papanicolaou tests from patients who received tamoxifen therapy. Patients with small blue cells in their Papanicolaou tests were an average of 9 years older at the time tamoxifen therapy was initiated than those without. Among the available follow-up surgical biopsies, no malignant diagnoses were made. CONCLUSIONS: We conclude that these distinctive small blue cells are found more frequently in older patients and most probably represent proliferative reserve cells of cervical/vaginal epithelium resulting from the estrogenic agonist effect of tamoxifen. More importantly, they are nonneoplastic in nature.

Quantitation of lipid-laden macrophages in evaluation of lower airway cytology specimens from pediatric patients.

Quantitation of lipid-laden macrophages has been used as a tool in the diagnosis of aspiration-related respiratory disorders. Fifty-six respiratory specimens from pediatric patients with lung diseases were retrospectively reviewed, and lipid-laden macrophage indices were evaluated according to modified published grading methods. The indices from patients at high risk for aspiration were significantly different from those at low risk. A simpler and more reproducible grading method was introduced. An important issue regarding sample adequacy was also addressed.

Accuracy, utility, and cost of frozen section margins in head and neck cancer surgery.

OBJECTIVES: Intraoperative frozen section analysis of surgical margins is widely used in head and neck cancer surgery. This study evaluates frozen section accuracy relative to permanent controls and final margins from the entire specimen, the rate at which frozen sections impact intraoperative management, and the resultant cost. STUDY DESIGN: Retrospective. METHODS: From 1997 to 1999 the frozen section results, permanent controls, and final tumor margins from 80 consecutive patients undergoing 420 intraoperative frozen section margins for head and neck malignancy were reviewed. RESULTS: A 98.3% accuracy rate (sensitivity, 88.8%; specificity, 98.9%) was found compared with permanent sections of the same tissue. However, 40% (8 of 20) of patients with positive final margins on the resection specimen, and 100% (15 of 15) with close (<5 mm) margins were not detected by frozen section analysis. The overall accuracy of frozen section in the evaluation of close or positive final margins was 71.3% (sensitivity, 34.3%; specificity, 100%). In addition, 5% (4 of 80) of patients potentially benefited from intraoperative frozen section by virtue of immediate margin revision. The estimated cost of intraoperative frozen section averaged as much as $3,123 per patient, with a cost-benefit ratio of 20:1. CONCLUSIONS: Intraoperative frozen section margins are accurate, but they are costly and cannot reliably eradicate positive final margins. Patients with early-stage lesions and those undergoing re-resection for recurrence or salvage surgery after radiation failure derived the greatest potential benefit from frozen section margins.

Adult herpetic laryngitis with concurrent candidal infection: a case report and literature review.

Rarely, adult herpetic laryngitis without involvement of the oropharynx has been reported. However, to our knowledge, laryngitis caused by herpes simplex virus with coexisting Candida albicans has not been reported. We report what we believe to be the first case of localized herpetic laryngitis superimposed by laryngeal Candida species infection in an immunosuppressed patient. This diagnosis was made on the basis of the findings of a laryngeal mucosal biopsy and ancillary testing using fungal stains and immunohistochemical stains for herpetic antigens. We also review the literature and discuss the clinical and diagnostic presentations, including potential pitfalls in the diagnosis.

The clinical application and cost analysis of fine-needle aspiration biopsy in the diagnosis of mass lesions in sarcoidosis.

BACKGROUND: Sarcoidosis is a prevalent disease of unknown cause characterized by granulomatous inflammation that often creates deep and/or superficial mass lesions. Tissue samples are considered the "gold standard" in diagnosis; however, it is a medically treated disease. We analyzed the utility and relative cost-effectiveness of fine-needle aspiration biopsy (FNAB) in the clinical investigation of patients with both suspected and unsuspected sarcoidosis. METHODS: All FNAB cases with sarcoidosis either as the cytologic diagnosis or mentioned as part of the differential diagnosis were retrospectively reviewed for clinical history, follow-up, cytologic features, and surgical pathology findings. Comparative analysis of cost of FNAB and excisional biopsy were also made. RESULTS: Thirty-two FNABs in 28 patients included 17 women and 11 men. Anatomic sites included lymph node (n = 17), lung (n = 5), salivary gland (n = 8), and liver (n = 2). Sarcoidosis had already been diagnosed or was a clinical consideration prior to FNAB in 14 cases. Chest radiograph showed abnormal findings in 19 cases. Angiotensin-converting enzyme (ACE) was measured in seven patients and was elevated in four. All aspirates showed granulomatous inflammation; in 22 patients, special stains or cultures for microorganisms were negative. Simultaneous or subsequent excisional biopsies confirmed the FNAB findings in 17 patients. Institutional ratios of excisional biopsy to FNAB in the diagnosis of sarcoidosis ranged from 4 to 19:1. The cost of FNAB was only 12.5 to 50% that of tissue biopsy. CONCLUSIONS: FNAB appears to be underutilized in the diagnosis of sarcoidosis. When used in conjunction with radiologic and laboratory data, FNAB may be a reliable and cost-effective method of diagnosis, especially in patients with an established diagnosis of sarcoidosis.

Diagnosis of papillary carcinoma in a thyroglossal duct cyst by fine-needle aspiration biopsy.

The incidence of papillary thyroid carcinoma arising in a thyroglossal duct cyst is rare and occurs in about 1 % of thyroglossal duct cysts. Only 17 such cases diagnosed with fine-needle aspiration biopsy have been previously reported in the English-language literature, with a diagnostic rate of 53%. In this article, the cytologic features of the current case are emphasized and those of the previous reported cases are briefly reviewed. Diagnostic pitfalls of papillary carcinoma arising in thyroglossal duct cysts diagnosed by fine-needle aspiration biopsy are also discussed.

Pleural fluid cytology of Hodgkin's disease: cytomorphologic features and the value of immunohistochemical studies.

Two cases in which Hodgkin's disease (HD) was cytologically diagnosed in pleural effusions are presented. The presence of Reed-Sternberg (R-S) cells was confirmed by positive staining for both CD15 and CD30, and negative staining for leukocyte common antigen. In addition, the differential diagnosis of HD in effusion cytology is presented, including look-alikes of R-S cells that can potentially lead to an incorrect diagnosis. To the best of our knowledge, we believe this is only the second cytologic report of HD diagnosed in a pleural effusion using immunohistochemistry to confirm the diagnosis.

Transitional cell carcinoma arising in a pyelocaliceal cyst. An unusual cystic renal lesion with cytologic and imaging findings.

The differentiation between benign and malignant cystic lesions of the kidney is a diagnostic challenge. Medical imaging aids in this task, but many cystic renal lesions require further work-up, frequently by computed tomography-guided fine needle aspiration. We report on the pathological findings in a case of moderately differentiated papillary transitional carcinoma, which arose in a pre-existing pyelocaliceal cyst in a 53-year-old man. In the case of this lesion, the distinction between a benign and a malignant renal cyst is blurred. To our knowledge, this is the third such occurrence to be reported and the first to be diagnosed by fine needle aspiration biopsy.

Anti-alpha-inhibin: marker of choice for the consistent distinction between adrenocortical carcinoma and renal cell carcinoma in fine-needle aspiration.

BACKGROUND: Anti-alpha-inhibin, an antibody directed against a peptide hormone, has been shown to be a useful diagnostic aid in surgical pathology material for the identification of sex cord-stromal neoplasms and recently has been described in adrenocortical carcinoma (ACC). The diagnosis of ACC versus renal cell carcinoma (RCC) may be difficult morphologically, particularly in fine-needle aspiration (FNA) material. To date, the immunohistochemical distinction of ACC from RCC is based on a panel of antibodies that include vimentin, cytokeratins, and epithelial membrane antigen. However, the reliability of this panel is weakened by inconsistent staining patterns. METHODS: Archival formalin fixed, paraffin embedded cell block sections from 45 FNAs of known primary and metastatic ACC and RCC as well as benign adrenocortical nodules were stained with anti-alpha-inhibin using an avidin-biotin procedure. All samples were microwave pretreated and a biotin block was performed to reduce the background stain due to the high endogenous biotin often present in these types of samples. RESULTS: All cases of ACC (n = 7; 100%) and benign adrenocortical cells (n = 15; 100%) were immunoreactive with the a-inhibin antibody, showing a diffuse cytoplasmic and granular staining pattern. The staining intensity and number of immunoreactive cells varied within each sample, with the cases of ACC having the greatest proportion of immunoreactive cells and the strongest intensity. None of the cases of RCC (n = 23; 0%) were immunoreactive with anti-alpha-inhibin. CONCLUSIONS: The morphologic distinction of ACC versus RCC in FNA material from renal, adrenal, and metastatic neoplasms is not always feasible based on cytology alone. However, due to the advent of the alpha-inhibin antibody, the reliable distinction of these entities now may be possible. The intense and specific immunostaining pattern for cells of adrenal origin, even in paucicellular samples, suggests potential for the widespread clinical utility of this marker by cytopathologists.

Diagnosis of infectious diseases: a cytopathologist's perspective.

This review explores the role of the cytopathology laboratory in the detection and presumptive identification of microorganisms. Sample procurement by exfoliation, abrasion, and aspiration techniques, as well as a variety of cytopreparatory and staining methods, is reviewed. Emphasis is placed on the utility of fine-needle aspiration as a rapid, safe, and cost-effective diagnositic procedure. The role of rapid interpretation and specimen triage is also discussed. Cytomorphologic features and staining characteristics are presented for a spectrum of microorganisms potentially encountered in the cytopathology laboratory. Pitfalls in diagnosis and the usefulness of special stains and ancillary techniques are also evaluated. The importance of communication, collaboration, and clinical correlation is stressed.

Diagnostic value of brush cytology in the diagnosis of duodenal, biliary, and ampullary neoplasms.

Endoscopy is a valuable tool in the diagnosis and management of duodenal lesions and biliary strictures. We assessed the value of cytology in the evaluation of these lesions and analyzed the causes of discrepancy among clinical, histologic, and cytologic parameters. The study included 118 patients with duodenal ulcers, ampullary neoplasms, or biliary strictures who were examined between 1975 and 1995; 120 cytologic examinations were performed. The specimens included brushings of the duodenum (DB, n = 50), ampulla (AB, n = 32), and biliary ducts (BB, n = 38). Endoscopic biopsies performed concurrently included the duodenum (n = 37), the ampulla (n = 22), and the biliary ducts (n = 23). Comparison of cytologic and histologic results showed the following sensitivity and specificity: DB, 40% and 97%, respectively; AB, 100% each; BB, 75% and 93%, respectively. The DB, AB, and BB revealed malignant neoplasms in 2 of 5, 7 of 7, and 6 of 8 cases, respectively. Twenty-three duodenal neoplasms were diagnosed by either modality and included 11 adenocarcinomas, 9 villous tumors, 2 metastatic renal cell carcinomas, and 1 large cell non-Hodgkin's lymphoma. Endoscopic brush cytology is an effective means of diagnosing ampullary neoplasms, and it complements tissue biopsy in cases of bile duct stricture. Location, predominance of tumor-induced stroma, an extramucosal growth pattern, sampling error, and interpretative experience influence the diagnostic evaluation. Cytologic diagnosis of an adenoma does not exclude an underlying malignant neoplasm in ampullary tumors. In some instances, it may be difficult to distinguish between villous tumors with severe dysplasia and adenocarcinomas by cytology alone.

Aspiration cytology of malignant neoplasms associated with granulomas and granuloma-like features: diagnostic dilemmas.

BACKGROUND: 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). METHODS: Clinical data, FNAC, and follow-up surgical specimens from six patients presenting with neck masses were reviewed. RESULTS: Only one case was diagnosed confidently as metastatic squamous cell carcinoma with an extensive granulomatous response; the other five were interpreted as "atypical" with descriptive cytology and a differential diagnoses including granulomatous inflammation, in addition to a caveat of "cannot exclude malignancy." Biopsy studies in these cases were recommended in view of the atypical cytologic findings and strong clinical suspicion of malignancy in each case. The histologic findings in two cases revealed Hodgkin's disease with exuberant granulomatous response. The remaining three cases were found to be malignant neoplasms with epithelioid morphologic features and included one example each of diffuse large cell lymphoma, anaplastic carcinoma of the thyroid, and lymphoepithelial carcinoma. CONCLUSIONS: Malignancies associated with granulomas and tumor cells mimicking epithelioid histiocytes may be difficult to diagnose accurately on FNAC. The cytologic differential diagnosis of a "granulomatous" process should include malignant neoplasms. Excisional biopsy studies may be required for definitive diagnosis.

Another quality assurance issue--amended reports: what do we really know about them?

The Clinical Laboratory Improvement Amendment (CLIA) of 1988 requires that if a cytology/histology discrepancy is discovered which is significant and affects patient care, an amended report should be issued (Clinical Laboratory Improvement Amendments, Fed Reg 1992;57:7169). Since little is known about such amended reports, a survey was developed to assess how individuals handle discrepancies. The Quality Assurance Task Force from the Papanicolaou Society of Cytopathology created a survey to assess these methods and sent it to all of their members. Fifty-one individuals responded to the survey. Methods vary widely among institutions. On average, 107 cytologic/histologic correlations are performed each month with the discovery of approximately 2 major and 11 minor discrepancies. Thirty-nine responders utilize written amended reports and telephone clinicians when a major discrepancy is found. Thirty-eight individuals indicated that their place of employment has a written policy concerning discrepancies. Time spent in quality assurance issues averaged 8 hr per wk for cytotechnologists and 3 hr per wk for pathologists. Although amended reports are required when significant discrepancies are revealed, a standard practice does not exist.

Basaloid squamous carcinoma metastatic to renal-cell carcinoma: fine-needle aspiration cytology of tumor-to-tumor metastasis.

We describe an unusual case of a basaloid squamous-cell carcinoma (BSCC) of the tonsil in a 56-yr-old man that metastasized to a primary renal-cell carcinoma (RCC) and the lung. The diagnosis of the second primary, the RCC, was based on fine-needle aspiration (FNA) cytology. A subsequent nephrectomy specimen revealed BSCC metastatic to RCC, clear-cell type. Retrospective analysis of the FNA of the renal mass revealed classic RCC morphology and, in addition, another cytologically distinctive pattern characterized by occasional sheets of cohesive neoplastic cells with hyperchromatic nuclei and nuclear molding representative of BSCC. The cytologic features of a subsequent FNA of the lung were characteristic of metastatic BSCC. Our retrospective analysis of cytologic material from the renal mass underscores the importance of raising the possibility of tumor-to-tumor metastasis when distinctly different morphologic features are seen in an otherwise typical cytology of a neoplasm in patients with an already known or suspected second primary. To our knowledge, this case report is the first one documenting metastasis of BSCC to RCC.

Spindle-cell lesions of the mediastinum: diagnosis by fine-needle aspiration biopsy.

Spindle cells seen in fine-needle aspiration biopsy (FNAB) of the mediastinal lesions can be a component of a wide variety of benign and malignant conditions. Few of these conditions, however, are described in the FNA cytopathology literature. This review discusses the cytopathologic features, differential diagnoses, and potential pitfalls of a variety of lesions with a significant component of spindle cells encountered in mediastinal FNAB. The cytopathology files from four institutions were searched for cases of mediastinal FNAB containing a spindle-cell component that was a key or predominant cytologic feature of the diagnostic specimen. The cytomorphologic features of these cases were analyzed, and their differential features are discussed. Of 196 mediastinal FNABs, 22 (11%) were lesions with significant spindle-cell component: granulomatous inflammation (four); benign nerve sheath tumor (four); thymic cyst (two); spindle-cell thymoma (two); large-cell non-Hodgkin's lymphoma with sclerosis (two); nodular sclerosing Hodgkin's disease (two); liposarcoma (two); spindle-cell squamous carcinoma possibly arising in a teratoma (one); unspecified high-grade sarcoma (one); spindle-cell malignant melanoma (one); and nonspecific fibrous tissue (one). The cytologic features of each lesion were analyzed as an aid for accurate classification. These findings were correlated with radiologic and clinical information when available. The value of ancillary studies performed on aspirated material in selected cases was also reviewed. FNA of mediastinal lesions with significant spindle-cell morphology represents an infrequent and heterogeneous group of entities that may pose significant diagnostic challenges. This review presents the salient cytopathologic features of various spindle-cell lesions of the mediastinum with particular emphasis on differential diagnosis and pitfalls. The pathologist must use caution when interpreting these lesions and ancillary studies may be of significant value in selected cases.

Diagnostic pitfalls in fine-needle aspiration biopsy of the mediastinum.

A retrospective review of 189 fine-needle aspiration (FNA) biopsies of the mediastinum from four university medical centers was performed. Review of Diff-Quick- and Papanicolaou-stained direct smears was performed from a series of 189 FNA biopsies along with surgical pathology correlation obtained in 42% of the cases. There were 28 (14.8%) nondiagnostic or unsatisfactory for diagnosis cases. Of the satisfactory FNA specimens with histologic correlation, 12 cases (6%) were discordant. These errors primarily involve subclassification of small-cell malignancies involving the mediastinum, including a misdiagnosis of small-cell carcinoma for lymphoma. Large-cell lesions that were problematic included the accurate diagnosis of Hodgkin's lymphoma including the separation from non-Hodgkin's lymphoma. Large-cell lymphoma with sclerosis was misinterpreted in two cases due to distortion of cells by the mesenchymal tissue and sparsely cellular smears. In two cases classification of primary germ-cell tumors and separation from metastatic carcinoma was a problem. In general, FNA of the mediastinum is an accurate procedure, but can be challenging in a minority of cases due to sparse cellularity of the lesions and accurate classification of a variety of neoplasms that occur in this region. These 12 discordant cases serve as the basis of our report.

Cytology of germ cell tumors: extragonadal, extracranial masses and intraoperative problems.

BACKGROUND: Germ cell tumors (GCTs) and their metastases may be found in numerous sites that are accessible to cytologic sampling, and many are responsive to chemotherapy. METHODS: The authors reviewed 20 examples of GCT cytology from 16 males and 3 females ranging in age from 1.5 to 61 years (median, 34 years). With two exceptions, one benign cystic ovarian teratoma in which intraoperative cytology was used to diagnose an associated adult-type carcinoma and one undescended testis in which seminoma presented as an abdominal mass, the material reviewed included no examples of primary gonadal GCT. RESULTS: The authors studied 7 primary and 13 metastatic GCTs; these studies were based on 13 in vivo aspirations, 4 intraoperative preparations, and 3 samples of body cavity fluids. All samples were correctly interpreted as malignant, and only one was incorrectly classified as a non-GCT malignancy. CONCLUSIONS: Clinical and cytologic findings are useful in the diagnosis of GCTs and their metastases. Incorrect interpretation of these neoplasms as poorly differentiated malignancies of other types may deprive the patient of effective chemotherapy. Air-dried, Romanowsky-stained smear material and cell block sections may contribute to the resolution of diagnostic dilemmas.