Can renal oncocytomas be distinguished from renal cell carcinoma on fine-needle aspiration specimens? A study of conventional smears in conjunction with ancillary studies.

BACKGROUND: The reliability of using fine-needle aspiration (FNA) to distinguish renal oncocytoma (RO), a benign tumor, from renal cell carcinoma (RCC), which has eosinophilic granular cytoplasm, has been questionable. However, it is clinically significant, because radical nephrectomy may be avoided in patients with RO. The authors retrospectively studied the cytologic features and ancillary study findings of RO compared with findings in RCCs with eosinophilic granular cytoplasm to evaluate the reliability of FNA-based diagnosis of RO. METHODS: The authors reviewed 19 tumors, including 11 ROs, three chromophobe RCCs (CRCCs), three granular variant RCCs (GRCCs), and two eosinophilic variant papillary RCCs (EPRCCs). Smears and cell blocks were prepared using either computed tomography-guided or ultrasound-guided FNA material. Surgical specimens were available for all tumors. Cytokeratin, vimentin, and Hale colloidal iron (HCI) stains were performed on all 19 tumors. Electron microscopy (EM) was available for six tumors. RESULTS: Although most tumors demonstrated their classic cytologic features, the specific diagnosis using conventional smears or even core biopsies was difficult in some tumors, especially ROs, due to the overlapping cytomorphology among these tumors. Cytologic material was obtained from 10 of 11 RO specimens. Of 10 ROs, 8 original FNA-based diagnoses were oncocytic neoplasm. Immunoperoxidase studies revealed that all tumors of each type were positive for cytokeratin, whereas only GRCCs and EPRCCs were positive for vimentin. The two vimentin negative neoplasms, RO and CRCC, could be distinguished by HCI stain, which showed diffuse or focal cytoplasmic positivity in CRCCs and apical/perinuclear staining (73%) or negative staining (27%) in ROs. Ultrastructurally, cytoplasm densely packed with mitochondria was characteristic for oncocytoma. CONCLUSIONS: This study demonstrated that ROs can be distinguished reliably from RCCs on the basis of cytologic morphology combined with ancillary studies, including immunostaining with cytokeratin and vimentin antibodies and HCI stain. EM provides additional information to confirm the diagnoses.

Metastatic small-cell carcinoma of the prostate diagnosed by fine-needle aspiration biopsy.

Fourteen fine-needle aspiration biopsies (FNABs) of metastatic small-cell carcinoma done on 12 patients who had histologically documented primary small-cell carcinoma of the prostate are described. The FNABs were of lymph node (four cases), liver (four cases), bone (two cases), pancreas (one case), perirectal soft tissue (one case), perineum (one case), and lung (one case). One patient underwent three FNABs. No patient had a second primary tumor elsewhere. Cytologic smears were cellular with numerous single tumor cells, many apoptotic bodies, and variable numbers of mitotic figures. Tight cell clusters with molded nuclei and finely stippled chromatin were seen in all cases. An organoid pattern of tumor cells was seen focally in two cases. Features distinguishing small-cell carcinoma from poorly differentiated prostate carcinoma were cell size, finely stippled chromatin, inconspicuous nucleoli, and numerous single tumor cells. Distinction from small-cell carcinoma of other primary sites requires clinical and radiologic correlation. We conclude that cytologic specimens are useful for documenting metastatic small-cell carcinoma of the prostate and for differentiating between it and conventional prostate carcinoma in metastatic sites.

Percutaneous techniques for the diagnosis and treatment of localized Langerhans-cell histiocytosis (eosinophilic granuloma of bone).

We retrospectively studied the outcome of percutaneous needle biopsy and intralesional injection of a corticosteroid (methylprednisolone) in thirty-nine patients who had localized Langerhans-cell histiocytosis (eosinophilic granuloma of bone). All thirty-nine patients had a solitary symptomatic lesion at presentation; a second lesion developed in two patients, two and four months after the first lesion was diagnosed. Therefore, there were forty-one lesions in thirty-nine patients. Fine-needle aspiration with or without core-needle biopsy was performed for all forty-one lesions, and the diagnosis of Langerhans-cell histiocytosis was established for thirty-seven (90 per cent). A corticosteroid was injected into thirty-five lesions. Twenty-nine received the injection at the time of the fine-needle aspiration on the basis of the cytological findings in the aspirate. Six patients who had a solitary lesion had a two-stage procedure because the injection was delayed until the diagnosis was confirmed with histological evaluation of specimens obtained by core-needle biopsy. Thirty-four (97 per cent) of the thirty-five lesions healed. The clinical symptoms associated with thirty-one lesions resolved within two weeks after a single injection of the corticosteroid. There were no complications associated with either the biopsy or the injection. At a median of ninety months (range, twenty-four to 199 months), no patient had recurrence of symptoms or of radiographic evidence of the lesion. All patients who had been managed with an intralesional injection of the corticosteroid had full range of motion of the affected extremity and had resumed unlimited activities. Although the mechanism of action of intralesional injection of a corticosteroid has not been defined, use of percutaneous needle biopsy to diagnose localized Langerhans-cell histiocytosis and treatment with intralesional administration of methylprednisolone relieved pain expeditiously, enabled the patient to avoid an operative procedure, and resulted in osseous healing. The specific role of corticosteroid therapy remains to be determined by prospective, randomized studies.

Use of fine-needle aspiration biopsy in the evaluation of splenic lesions in a cancer center.

Fine-needle aspiration biopsy (FNAB) of the spleen was performed on 50 patients, of whom 40 had had a previous diagnosis of malignancy (23 lymphoproliferative disorders, 13 carcinomas, 3 melanomas, and 1 sarcoma). The cytologic diagnoses included 22 cases positive for malignancy (10 lymphomas, 9 metastatic carcinomas, 2 metastatic melanomas, and 1 sarcoma), 18 cases negative for malignancy, 4 cases suspicious for malignancy, and 6 nondiagnostic specimens. No major complications were associated with the FNAB procedure, however, one patient did develop a pneumothorax that resolved spontaneously. Subsequent splenectomy was performed in 10 of the 50 cases. There were no false-positive diagnoses, and only one false-negative diagnosis, which was attributed to sampling error. The aspirate, showing only benign splenic parenchyma, was from a patient with splenomegaly and no previous diagnosis; subsequent splenectomy showed acute myelogenous leukemia. In our study, FNAB proved to be a safe and valuable diagnostic tool for evaluating splenic lesions in oncologic patients.

Percutaneous needle biopsy diagnosis of benign neurogenic neoplasms.

Preoperative diagnosis of benign neurogenic neoplasms (BNNs) provides useful information in guiding management. To assess the effectiveness of fine-needle aspiration (FNA) and needle core biopsy (NCB) in diagnosing schwannomas and neurofibromas, 40 percutaneous biopsies interpreted as BNNs or obtained from lesions subsequently shown by excision to be BNNs were reviewed. The 13 aspirates diagnostic of BNN revealed spindle cells arranged haphazardly in irregular tissue fragments and in parallel as elongated ropy fascicles, with a myxoid to fibrillary background. The nuclei were buckled, often with intranuclear cytoplasmic inclusions. Four lesions showed nuclear pleomorphism without mitoses. Of 19 schwannomas evaluated by FNA, four (21%) were diagnosed as schwannomas and seven (37%) as BNNs. Ten neurofibromas were aspirated, revealing two (20%) BNNs. Of seven nondiagnostic FNAs accompanied by NCB, three (43%) indicated a BNN. The sensitivities of FNA, NCB, and both modalities in diagnosing BNNs were 43,60, and 71%, respectively. For the 16 FNAs showing features of BNNs, subsequent excisions revealed 11 schwannomas, two neurofibromas, one neurogenic sarcoma, one fibromyxoid neoplasm of uncertain malignant potential, and one unclassified low-grade myxoid sarcoma. FNA can be effective in diagnosing BNNs. If collagenous or myxoid lesions yield paucicellular nondiagnostic aspirates, NCB is helpful. Lowgrade sarcoma and neurofibromatous areas of neurogenic sarcoma may be misinterpreted as BNNs by percutaneous biopsy. BNNs may show nuclear pleomorphism without mitotic activity, and should not be mistaken for sarcoma.

Fine-needle aspiration cytology of seminoma: a review of 16 cases.

We report the cytomorphologic features of 16 fine-needle aspiration (FNA) biopsies of seminoma obtained from 16 male patients. The aspirates included two primary gonadal tumors (one occurring in a cryptorchid testis), two primary mediastinal tumors, and 12 metastases (two with unknown primaries). Analysis of the aspirates revealed a primarily dispersed cell population of large cells with scant to moderately abundant cytoplasm. The nuclei were round to slightly irregular, had finely granular chromatin, and had either one central prominent nucleolus or two to three smaller nucleoli. Variable numbers of lymphocytes and plasma cells were intermingled with the tumor cells. Only a few cases had epithelioid histiocytes or the characteristic "tigroid" background. The cytologic features of the metastases were distinctive and were considered diagnostic for therapeutic management. In six cases, an initial diagnosis of seminoma by FNA biopsy identified the neoplasm as germ cell in origin rather than other neoplasms in the differential diagnosis, thereby expediting therapeutic management.

Core needle biopsy and fine-needle aspiration in the diagnosis of bone and soft-tissue lesions.

Although core needle biopsy (CNB) and fine needle aspiration (FNA) procedures are widely used for the diagnosis of epithelial neoplasms, these procedures have not gained popularity on patients suspected of having bone or soft-tissue neoplasms. This article describes the University of Texas, M.D. Anderson Cancer Center experience with CNB and FNA procedures in bone and soft tissue performed in over 800 patients.

Diagnosing intramuscular myxoma by fine-needle aspiration: a multidisciplinary approach.

The gross and microscopic appearances of aspirates from ten intramuscular myxomas are reported. The specimens were obtained from seven women and three men, ages 43 to 75, who had tumors involving the muscles of the thigh (7), upper arm (2), and forearm (1). Magnetic resonance (MR) imaging performed in six of the ten cases revealed well-defined, sharply demarcated tumors exhibiting low signal intensity relative to muscle on the T1-weighted images. The tumors were hyperintense to muscle on T2-weighted images. All aspirated tissues were clear, tenacious, and viscous. Smears contained few spindled and histiocytoid cells in an abundant mucoid background. Spindle cells demonstrated long cytoplasmic processes that in areas intertwined to form fibrillar tangles. Nuclei were oval to spindled with fine chromatin and inconspicuous nucleoli. Capillaries were sparse with simple (non-plexiform) branching. The differential diagnosis of myxoid lesions of the extremities includes benign entities such as myxoid schwannoma and neurofibroma, mesenchymal repair, and ganglion cyst, as well as malignant neoplasms such as myxoid liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, and extraskeletal chondrosarcoma. The findings of this study revealed that, although the cytologic features were suggestive of intramuscular myxoma, a definitive diagnosis was often difficult, owing to scant cellularity and lack of distinctive cytologic features. The MR imaging findings may be utilized as an adjunct to the cytologic features to more confidently suggest a diagnosis of intramuscular myxoma.

Cytology of malignant melanoma of soft parts: fine-needle aspirates and exfoliative specimens.

We describe the morphologic features of 25 cytology specimens (13 fine-needle aspirates and 12 exfoliative specimens) obtained from nine patients with malignant melanoma of soft parts (MMSP). Analysis of the fine-needle aspirates and exfoliative specimens revealed primarily a dispersed cell population with occasional cell clustering. Tumor cells were round to polygonal with moderately abundant cytoplasm and had round nuclei with prominent nucleoli. In two cases, an initial definitive diagnosis of MMSP was rendered on material obtained by fine-needle aspiration with the aid of immunocytochemical and ultrastructural studies.

Fine-needle aspiration cytology of the male breast in a cancer center.

All fine-needle aspirates (FNA) performed on the male breast at The University of Texas M. D. Anderson Cancer Center from 1985 to 1992 were reviewed, totaling 64. The patients' ages ranged from 19 to 86 years, with a mean of 56 years. Thirty-three patients had a history of an extramammary malignancy. The diagnoses established by FNA were gynecomastia (45), mammary carcinomas (6), neoplasms metastatic to the breast (5), suspicious for carcinoma (1), intra-mammary lymph node (1), and lipoma (1). In five cases the aspirates were nondiagnostic. Two of these proved to be gynecomastia on subsequent histologic examination. Of the six FNA cases initially thought to represent primary breast carcinomas, two were found to be secondary because of involvement of the underlying chest wall by mesothelioma (1), and mucinous adenocarcinoma, unknown primary (1). No false-positive diagnosis was rendered. We conclude that fine-needle aspiration of the male breast is a reliable means of assessment; however, unique problems may be encountered compared with aspiration of the female breast. These include the epithelial hyperplasia frequently associated with gynecomastia, the relatively equal frequency of primary and metastatic breast lesions when a malignant process is discovered, and chest wall lesions masquerading as breast lesions.

Fine-needle aspiration of intra-abdominal desmoplastic small cell tumor.

The cytologic features of four cases of histologically confirmed intra-abdominal desmoplastic small cell tumor (DSCT) that occurred in males between 18-27 yr of age are presented. Smears showed small cells with scant cytoplasm which were primarily arranged in loosely cohesive clusters. Nuclei were oval to round with evenly distributed, finely granular chromatin and inconspicuous nucleoli. As is typical of DSCT, the cells strongly expressed keratin and desmin in all cases. In the one case studied by electron microscopy, it was demonstrated that the cells were joined by small junctions and contained paranuclear aggregates of intermediate filaments. The absence of the characteristic desmoplastic stroma in DSCT aspirates and the nonspecific cytologic features of this small round-cell tumor (SRCT) made cytologic interpretation difficult. Cytopathologists should be aware of this entity so that DSCT is included in the differential diagnosis of SRCTs that occur in intra-abdominal sites. A panel of markers that includes keratin and desmin should be used to assist in the identification of DSCT.

Quality-assurance study of simultaneously sampled, non-correlating cervical cytology and biopsies.

As part of a quality assurance study, we reviewed 223 cases of simultaneously sampled cervical smears and biopsies that showed a significant lack of correlation for squamous dysplasia or carcinoma. In 153 of the 223 cases (68.6%), the cytology was negative and the biopsy positive. After review of the specimens, errors in this group were found to be of the following types: sampling 64%, interpretive 29%, and combined sampling and interpretive 7%. In the remaining 70 cases (31.4%), the biopsy was negative and the Papanicolaou smear positive. In these cases, the following types of errors occurred: sampling 54%, interpretive 33%, and combination 13%. Twenty-nine of these 70 patients showed dysplasia on follow-up material. These findings indicate there are a significant number of false-negative Papanicolaou smears, mostly because of sampling problems. There are few false-positives. In cases of positive Papanicolaou and negative biopsy, dysplasia is likely to be present in subsequent samples.

Diagnosis of eosinophilic granuloma of bone by fine-needle aspiration with concurrent institution of therapy: a cytologic, histologic, clinical, and radiologic study of 27 cases.

Twenty-seven patients with eosinophilic granuloma (EG) of bone seen at our institution between 1979 and 1991 underwent fine-needle aspiration (FNA) with or without concurrent Tru-Cut biopsy. The 16 males and 11 females ranged in age from 2 1/2 to 61 years (median, 10 yr). Twenty-four patients had monostotic lesions. The clinicoradiologic differential diagnosis included osteomyelitis and Ewing's sarcoma (young patients) and primary and metastatic malignancies (older patients). Twenty-four of 28 FNAs (one patient had two FNAs) were diagnostic of EG, and 10 cases were diagnosed by FNA alone. Smears in these cases showed histiocytes, often with grooved or infolded nuclei, and abundant eosinophils. Multinucleated giant cells, foamy histiocytes, neutrophils, lymphocytes, and plasma cells were present in variable numbers. Four FNAs were misdiagnosed: two as osteomyelitis where smears contained abundant neutrophils, sparse eosinophils, and histiocytes misinterpreted as foamy histiocytes, and two as metastatic carcinoma (in adults) where histiocytes in a scant specimen (one case) and skin appendiceal structures without lesional tissue (one case) were misinterpreted. These cases were correctly diagnosed on repeat FNA (one case), Tru-Cut (two cases), or excisional biopsy (one case); however, three cases diagnosed by FNA had nondiagnostic concurrent Tru-Cut biopsies. Treatment consisted of intralesional injection of 125 mg of methylprednisolone (22 cases). Progressive or complete healing of all lesions occurred. FNA is a rapid and useful technique for the immediate diagnosis of EG that allows concurrent institution of therapy.

Spindling artifact of urothelial cells in post-laser treatment urinary cytology.

We reviewed 22 post-laser (Nd:YAG laser) coagulation bladder washes collected immediately after treatment. All washes demonstrated a striking artifact of cellular spindling. These spindled cells occurred singly, in loose clusters, and in lamellar stacks and had elongated nuclei with dense chromatin and bipolar cytoplasm that was fused in the stacks. Concurrent biopsies demonstrated similar cytologic changes. The spindling is a nonspecific epithelial response to heat. Conventionally electrocauterized epithelia show this artifact in biopsies, but since only the base of the lesion and surrounding urothelium are subjected to heat with electrocautery, the relatively few spindled epithelial cells created presumably go undetected in cytology specimens. With laser treatment, however, the whole urothelial surface of the lesion is coagulated, producing a much greater number of spindled cells. It is important to avoid misinterpreting the spindled cells as cells from a mesenchymal neoplasm or a sarcomatoid carcinoma, mistakes that were made in some of our initial cases. Malignancy cannot be evaluated when cells exhibit spindling artifact; this judgement should be made on undistorted cells. Thus, pre-laser and post-laser washes should be submitted for evaluation of malignancy.

Peritoneal washing cytology in women: diagnostic pitfalls and clues for correct diagnosis.

The significance of peritoneal washing cytology in the management of patients with gynecologic cancer is well established. Its microscopic evaluation, however, is not always straightforward. Previous studies have identified some of the conditions that may result in misinterpretation of cytologic results. This report reviews the literature and describes other sources of diagnostic difficulties and clues for correct diagnosis. In addition, an outline for distinguishing endosalpingiosis from borderline and well-differentiated serous carcinoma is proposed.

Fine-needle aspiration cytology of alveolar soft-part sarcoma.

Alveolar soft-part sarcoma (ASPS) is a rare soft-tissue tumor. Few cases have been reported in the aspiration cytology literature. We discuss the fine-needle aspiration (FNA) cytologic features of ASPS in four patients. The smears were characterized by single cells and clusters of cells associated with thin-walled vasculature, resulting in a distinct pseudoalveolar pattern. The cells had abundant granular cytoplasm and large round nuclei with prominent central nucleoli. Binucleated and occasional multinucleated cells were present. Numerous stripped tumor nuclei were a consistent feature. Periodic acid-Schiff (PAS)-positive diastase-resistant granules were demonstrable within the intact and fragmented cytoplasm. Electron microscopy of aspirated material identified granules and crystals with the characteristic lattice pattern. To conclude, the FNA cytologic features of ASPS are characteristic. Confirmation by special stains and electron microscopy of FNA material is possible. The differential diagnostic considerations include renal cell carcinoma, paraganglioma, granular cell tumor, clear cell sarcoma, and epithelioid sarcoma.

Fine needle aspiration cytology of chondroblastoma of bone.

Between 1979 and 1987 12 patients with chondroblastoma underwent fine needle aspiration (FNA). There were eight female and four male patients (age range, 11-35 years) with lesions of the proximal humerus (three cases), distal femur (two cases), proximal tibia (two cases), proximal femur, distal tibia, talus, navicular bone, and fifth metacarpal (one case each). The radiologic features of the tumors were not entirely typical of chondroblastoma in the majority of patients. The aspirate was diagnosed as chondroblastoma in seven cases, was considered strongly suggestive of chondroblastoma in one case, was found to be diagnosable as chondroblastoma on review in one case, and was nondiagnostic in two cases. The remaining case, which showed giant cell tumor-like areas in addition to typical chondroblastoma on histologic sections from the curettage, was interpreted as giant cell tumor on FNA. There was no case in which an aspirate was erroneously diagnosed as chondroblastoma. On FNA, chondroblastoma had three dominant cytologic components: neoplastic mononuclear cells (chondroblasts), multinucleated osteoclast-like giant cells, and chondroid matrix fragments. The chondroblasts tended to lie individually in smears creating a pebbled appearance. They most commonly had round to oval nuclei with fine, evenly distributed chromatin and distinct longitudinal grooves, but indented, lobulated, and pyknotic nuclei were also observed. Their cytoplasm was dense and opaque with rounded well-defined borders. Multinucleated osteoclast-like giant cells were randomly admixed and were indistinguishable from those seen in other bone neoplasms. Chondroid matrix stained magenta with the Diff-Quik stain and green to violet with Papanicolaou. The cytologic features of the chondroblasts are the diagnostic hallmark of chondroblastoma and may allow FNA to become a valuable preoperative technique in the management of these patients.

Fine-needle aspiration cytology of peripheral T-cell lymphoma. A cytologic, immunologic, and cytometric study.

The diagnosis of peripheral T-cell lymphoma (PTCL) is difficult. This entity can be misdiagnosed as Hodgkin's disease or a reactive process such as nonnecrotizing granulomatous lymphadenitis or it can present a problem in lymphoma classification. Fine-needle aspirates from 13 patients with histologically proven PTCL were evaluated by cytology, immunochemistry, and flow cytometry. Of the 13 patients with PTCL, initial cytologic diagnoses were atypical lymphocytic infiltrate (2), mixed-cell lymphoma (6), mixed-cell lymphoma with associated histiocytes (2), large cell lymphoma (2), and small cell lymphoma (1). Surface marker studies were performed on cytospin preparations. Antibodies against cytotoxic-suppressor (Leu-2a) and helper-inducer (Leu-3a,b) antigens were used in 11 cases. Ten lymphomas demonstrated helper phenotype and one showed phenotypic heterogeneity in two different sites. The most prominent cytologic features of PTCL were a variable combination of small, intermediate, and large lymphoid cells with irregular nuclei, presence of epithelioid histiocytes, and atypical mononuclear cells. Flow cytometry studies showed a diploid stem line with intermediate proliferative activity (mean S-phase of 6.7%) in most cases, despite the clinical aggressiveness of this neoplasm.

Leukemic lymphadenopathy: diagnosis by fine needle aspiration.

We report cytologic findings in 6 patients (2 with a history of chronic myelogenous leukemia and 2 with a history of acute lymphoblastic leukemia) who presented with generalized or localized lymphadenopathy of undetermined etiology. Fine needle aspiration of enlarged lymph nodes resulted in the initial diagnosis of leukemia (1 case) or blast crisis of leukemia (2 cases), confirmation of involvement by leukemia at presentation (1 case), or confirmation of relapse of leukemia (2 cases). The average number of cells in the aspirates was 20 million, sufficient for performing immunophenotypic studies, flow cytometry, cytogenetic studies, and electron microscopy. The cytological features, combined with the ancillary studies, resulted in the diagnosis and subclassification of the leukemias as follows: chronic myelogenous leukemia, blast crisis (lymphoid); chronic myelogenous leukemia, blast crisis (undifferentiated); common acute lymphoblastic leukemia; acute lymphoblastic leukemia (T-cell), acute lymphoblastic leukemia (T-cell); and malignant lymphoma, small lymphocytic type.