Analysis of ret/PTC gene rearrangements refines the fine needle aspiration diagnosis of thyroid cancer.

Papillary carcinoma (PC) represents the most common malignancy of the thyroid gland. Therefore, the assessment of fine needle aspiration biopsies of thyroid nodules rests heavily on the identification of nuclear features of PC. The ret/PTC oncogene, formed by several gene rearrangements, is specific for PC among thyroid tumors. In this study we examined thyroid aspirates for the presence of ret/PTC gene rearrangements by RT-PCR and Southern hybridization. We prospectively collected thyroid aspirates in Cytolyt solution and prepared slides for cytological examination using the ThinPrep method. All remaining material was then used for nucleic acid extraction with subsequent RT-PCR for the housekeeping gene PGK-1 to ensure ribonucleic acid integrity, for thyroglobulin to ensure the presence of follicular epithelial cells, and for the three most common ret/PTC gene rearrangements (ret/PTC-1, -2, and -3). The results of the first 73 cases with surgical follow-up were correlated with the cytological diagnosis and final histopathology. ret/PTC gene rearrangements were detected in 17 of 33 samples (52%) that were PC on histopathology; the presence of gene rearrangements was confirmed by molecular analysis of corresponding surgically resected frozen tissue. There were no false positives. The identification of ret/PTC gene rearrangements refined the diagnosis of PC in 9 of 15 specimens (60%) that would otherwise have been considered indeterminate and in 2 of 6 that were considered insufficient for cytological diagnosis. The results indicate that RT-PCR for ret/PTC is a specific marker that can be applied to fine needle aspiration biopsies and improves the diagnosis of malignancy when used as an adjunct to traditional cytology.

The 4p- syndrome--an autopsy study.

The autopsy of an infant with the 4p- or Wolf-Hirschhorn syndrome revealed visceral abnormalities not previously described, i.e., agencies of the gallbladder and spleen. The parents' chromosomes were normal.

Estrogen and progesterone receptor contents in ThinPrep-processed fine-needle aspirates of breast.

This study was undertaken to assess the potential value of ThinPrep-processed (Cytyc, Boxborough, MA) smears from malignant breast fine-needle aspirates (FNAs) for the determination of estrogen receptor (ER) and progesterone receptor (PR) status. The ER and PR content of 142 malignant FNAs were compared with the results of the surgically excised tumors in which the assay was done by enzyme immunoassay in 97 cases or by immunohistochemistry in 45 cases. Monoclonal antibodies directed against ER-1D5 (Dako, Carpinteria, CA) and PR-1A6 (Dako) were used with the antigen retrieval technique. By using enzyme immunoassay and immunohistochemistry as standards, the overall accuracy for ER was 97% and for PR was 89%. The results of this study show that the ThinPrep smear with microwave antigen retrieval pretreatment is a reliable method and a suitable alternative for hormone receptor analysis in breast carcinoma.

Breast fine-needle aspiration. A comparison of ThinPrep and conventional smears.

Fine-needle aspiration (FNA) of the breast has been used in our institution since 1969. In August 1993, ThinPrep (Cytyc Corp, Boxbotough, MA) processing of breast FNA biopsy specimens was introduced. Comparing conventionally prepared breast FNA specimens (21,193 cases) with ThinPrep processed material (7,903 cases) shows a decrease in the unsatisfactory rate with the ThinPrep processing (29.5% to 27.7%) with no significant change in sensitivity (84.4% vs 86.3%) or positive predictive value (96.5 vs 95.0%). However, there is a slight decrease in specificity (98.6% vs 96.5%) and negative predictive value (91.1% vs 88.0%) with the ThinPrep specimens. The results span 28 years, during which time the breast cancer population has changed, with a higher prevalence of malignancy in the last decade of our study. When the 4 most recent years of conventional cytology are compared with the 4 years of ThinPrep processing, there is no significant difference in diagnostic accuracy. The results of the present study show that the ThinPrep processing technique provides an effective method for preparing breast FNA. specimens.

A papillary adenocarcinoma of the renal pelvis in a young girl. A light- and electron-microscopic study.

An unusual primary papillary renal pelvic tumor associated with calcareous uropathy was found in a young girl and was diagnosed, using light microscopy, as a papillary adenocarcinoma; electron microscopy showed similarities between the tumor-cell type and the cells normally found lining the collecting tubules or ducts of Bellini. The patient has been free of recurrence over a five year follow-up period.

Mucus-producing medullary cell carcinoma of the thyroid gland.

A case of medullary carcinoma of the thyroid with the presence of mucus-secreting (goblet) cells was reported. Ultrastructurally, the tumor was composed of two types of cells, one with neurosecretory granules and the other with mucus granules. The secretion of calcitonin and mucus was demonstrated by histochemical methods. The presence of two cell populations in this tumor casts doubts on the "APUD" concept, which proposes a neuroectodermal origin for parafollicular (C) cells of the thyroid gland. The significance of this tumor with regard to the histogenesis of the cells involved, is discussed.

Medullary carcinoma of the thyroid in fine-needle aspiration biopsies.

A study of fine-needle aspiration biopsies (FNAB) in six cases of medullary carcinoma of thyroid (MCT) revealed that the presence of spindle cells in addition to the more usually recognized polygonal cells is a common feature and a significant clue to the diagnosis. Both spindle and polygonal cells contain cytoplasmic granules that stain positively for calcitonin by the immunoperoxidase technic. Amyloid, when present, can be identified presumptively in the Papanicolaou stain. This can be confirmed by restaining with Congo red. Both immunoperoxidase staining for calcitonin and amyloid staining for Congo red work well on the decolorized Papanicolaou-stained smears.

Reappraisal of the value of testicular biopsy in the investigation of infertility.

One hundred and forty-two biopsies were reviewed to reappraise the value and indications for testicular biopsy in the investigation of infertility. These biopsies were categorized within the following morphologic patterns: normal, hypospermatogenesis, maturation arrest, Sertoli cell-only syndrome, and Klinefelter's syndrome. The morphology of the biopsies was correlated with the available sperm count, and the contribution of the biopsy to the patient's treatment was assessed. Testicular biopsy has proved most useful in azoospermia for the identification of obstruction. In oligospermia, biopsy appears to be of little use.

Ultrasound-guided fine-needle aspiration biopsy in the management of thyroid disease.

During a 23-month period, 59 patients were referred for ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) of the thyroid gland because of inadequate orthodox (office) FNAB, a clinically small lesion, or an occult lesion. Seventy percent of the group (41 patients) was referred for surgery, which revealed cancer in 37% of patients, adenoma in 19%, and benign disease in 44%. US-guided FNAB yielded false-positive reports in 0% of patients, false-negative reports in 5% to 12%, and inadequate aspirates in 32%. The US-guided FNAB technique had a sensitivity of 60% to 90%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 80%, and an accuracy of 85%. US-guided FNAB provides cytologic information in 60% of patients in whom a diagnosis cannot be established by orthodox (office) means, thus enhancing the diagnostic ability of clinicians who can recommend a treatment program with confidence.

Ultrasonography and ultrasound-guided fine-needle aspiration biopsy of head and neck lesions: a surgical perspective.

A head and neck ultrasound-guided fine-needle aspiration clinic was set up to determine the role of ultrasound and ultrasound-guided fine-needle aspiration in the evaluation of patients with lesions in this region. One hundred ninety-five lesions were biopsied by ultrasound-guided fine-needle aspiration in 203 patients. Ultrasound detected 2 or more lesions in 14 (48%) of 29 patients with a clinically solitary thyroid nodule. Three (8.8%) of 34 lesions thought to be within the parotid gland were determined to be external. A pronounced learning curve was evident in the technique of ultrasound-guided fine-needle aspiration, particularly for nonpalpable disease. Adequacy of sampling for each 3-month period was 71%, 89%, and 94%, respectively. Seventy-four percent of central aspirations were satisfactory compared to 54% of peripheral aspirations. Ultrasound-guided fine-needle aspiration did not alter the clinical staging of metastatic neck disease in 8 patients having 10 neck dissections but proved useful in detecting nodal recurrence in 3 irradiated necks that did not proceed to surgery. The smallest node to harbor malignancy had 4-mm maximal axial diameter. We conclude that ultrasound and ultrasound-guided fine-needle aspiration are valuable adjuncts to the clinical examination.

Rhabdomyosarcoma with rhabdoid-like features.

We describe an unusual case of a rhabdomyosarcoma (RMS) in that it had rhabdoid-like cells histologically and occurred in a female who had undergone bone marrow transplantation for chronic myelogenous leukemia. The tumor was composed of loosely cohesive cells with abundant eosinophilic cytoplasm and exhibited PAS-negative paranuclear inclusions. The tumor cells had positive vimentin, muscle-specific actin, sarcomeric actin and desmin immunoreactivity. Ultrastructurally, the tumor cells contained aggregates of thin and thick filaments. In situ hybridization did not detect human papillomavirus or cytomegalovirus DNA, or EBV DNA or RNA. The tumor fulfilled the current criteria for a diagnosis of RMS; however, it could not be further classified. The tumor appears to have a good prognosis as there has been no evidence of recurrence five years after resection. As this is the first case report, to our knowledge, of this type of tumor following bone marrow transplant, the significance of this association is not yet clear.

Intraosseous malignant peripheral nerve sheath tumor. Report of a case and review of the literature.

We report a case of a malignant peripheral nerve sheath tumor arising in the distal femur of a 28-year-old man who had no stigmata of von Recklinghausen's disease. Roentgenograms and computed tomographic scans of the distal femur showed a single lytic intraosseous lesion with minimal soft tissue extension. Light microscopy demonstrated a tumor composed of spindle cells with myxoid areas. There was some nuclear pleomorphism and mitotic activity. The tumor cells were immunoreactive for S100 protein and neuron-specific enolase. Ultrastructurally, there were cells with long processes, which were focally invested by basal lamina. Some cells had numerous micropinocytotic vesicles. The tumor recurred in the femur 15 months following the initial curettage. Computed tomographic scan of the lungs at that time showed a nodule, which has since enlarged. Primary osseous malignant peripheral nerve sheath tumors are uncommon. A literature review revealed only 18 previous cases, the majority of which occurred in the mandible or maxilla. This is a rare case of intraosseous malignant peripheral nerve sheath tumor of a long bone, with both immunohistochemical and ultrastructural confirmation of nerve sheath differentiation.

Primary leiomyosarcoma of bone: report of seven cases and review of the literature.

OBJECTIVE: To report seven cases of intraosseous leiomyosarcoma and compare them with the cases in the literature. DESIGN: Retrospective review of histologic, immunohistochemical, and ultrastructural features. Tumors were examined immunohistochemically for proliferative activity and p53 protein accumulation. SETTING: Mount Sinai Hospital, University of Toronto, Ontario, Canada. RESULTS: The histologic grade of the tumors ranged from I to III. All tumors showed vimentin and muscle-specific actin immunoreactivity and smooth muscle differentiation ultrastructurally. Proliferative activity was demonstrated immunohistochemically in five of the seven cases. Only one tumor showed p53 protein accumulation. CONCLUSION: Primary leiomyosarcoma of bone is an aggressive tumor with light microscopic, ultrastructural, and immunohistochemical features similar to leiomyosarcoma of soft tissue. The proliferative activity of these tumors does not appear to correlate with the histologic grade. p53 protein accumulation as detected by immunostaining is not common in these tumors.

Lambda-light-chain nephropathy with Fanconi's syndrome.

Renal disease is a common complication of paraproteinemia, but light-chain nephropathy with resultant Fanconi's syndrome is unusual. In a 60-year-old man with Fanconi's syndrome, the underlying disease was a well-differentiated lymphocytic lymphoma, with two paraproteins and lambda-light-chain proteinuria. A renal biopsy specimen showed crystals in tubular cells, more prominent in proximal than distal tubules. Immunoperoxidase studies confirmed the lambda-light-chain content of the crystals. All previous cases studied by biopsy have involved kappa light chains. Light chains are thought to be toxic to the tubular epithelium, resulting in Fanconi's syndrome. Case reports of lymphoproliferative disorders associated with paraproteinemia and Fanconi's syndrome suggest a somewhat better prognosis with this clinical entity.

Metastatic adamantinoma diagnosed by fine-needle aspiration biopsy of the lung.

We report two cases of metastatic adamantinoma to the lung diagnosed by FNAB. The cytologic appearance of the smears of each case was homogenous, containing small round and spindle cells with indistinct cytoplasm. The nuclei had delicate nuclear membranes, with finely dispersed chromatin and occasional micronucleoli. No pleomorphism was noted. Immunocytochemistry exhibited positive staining for keratin and vimentin. EM examination revealed numerous tonofilaments and well formed desmosomes. The cytologic diagnosis of metastatic adamantinoma can be made with the knowledge of a previous history of adamantinoma of bone, the comparison of the metastatic tumor with the original bone tumor, and the awareness of the long latency of the metastases. Immunocytochemistry and EM are needed to substantiate the diagnosis.

Fine-needle aspiration biopsy of hepatic angiosarcoma: report of a case with immunocytochemical findings.

Hepatic angiosarcoma (Kupffer cell sarcoma) is a very rare but ominous malignancy. We report a case diagnosed by fine-needle aspiration biopsy (FNAB). The smear showed malignant spindle cells and a few rounded cells. The diagnosis was made on the cell block by the characteristic scaffolding arrangement of malignant cells along preexisting hepatocytes. This is the first report with immunocytochemical findings. The tumour cells stained positively for vimentin and negatively for keratin, factor VIII, Ulex europaeus agglutinin I (UEA-1), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and lysozyme. This case demonstrates the possibility of a definitive diagnosis by FNAB prior to death without inflicting serious complications.

Fine needle aspiration of schwannomas. Value of electron microscopy and immunocytochemistry in the preoperative diagnosis.

In the absence of Verocay bodies, the cytologic appearance of schwannomas can be quite nonspecific, with the differential diagnosis including a number of spindle cell lesions. The diagnostic accuracy can be enhanced by the use of electron microscopy (EM) and immunocytochemistry; both techniques are easily applicable to aspirated material. Six cases of schwannoma, diagnosed as such preoperatively by the application of these techniques, are reported. Only two of the cases showed Verocay bodies on light microscopy. Electron microscopy, performed on four cases, revealed a complex arrangement of long cell processes, with scattered desmosomelike structures, a prominent focally reduplicated basal lamina and long-spacing collagen. All of the cases showed positive staining for S-100 protein.

Cytologic, ultrastructural and immunologic features of intracytoplasmic hyaline bodies in fine needle aspirates of hepatocellular carcinoma.

Intracytoplasmic hyaline bodies in malignant cells from an aspirate of a liver mass are suggestive of hepatocellular carcinoma. Such inclusions were studied by light and electron microscopy and by immunocytochemistry in fine needle aspirates from five cases of hepatocellular carcinoma. Seen by light microscopy, the inclusions were round or ovoid and were surrounded by a prominent halo. By both light and electron microscopic immunocytochemistry, the hyaline bodies showed negative staining for alpha-fetoprotein, alpha-1-antitrypsin and cytokeratin. Ultrastructurally, they were not membrane bound and were composed of filamentous, finely granular material, resembling the early stages of Mallory bodies.

Metastatic squamous carcinoma presenting as a neck cyst. Differential diagnosis from inflamed branchial cleft cyst in fine needle aspirates.

Fine needle aspirates (FNAs) from five cases of cystic squamous carcinoma metastatic to cervical lymph nodes were compared to those of five cases of branchial cleft cyst to determine whether these lesions could be differentiated by cytologic examination. Squamous carcinoma could be recognized by the following cytologic features: increased nuclear/cytoplasmic ratio, irregularity of nuclear outline and nuclear hyperchromatism. The branchial cleft cysts showed essentially benign squamous cells with only mild nuclear atypia. The background of the malignant aspirates showed more necrotic debris but fewer polymorphonuclear cells than that of the branchial cleft cysts. By adhering to these cytologic criteria a definitive diagnosis is possible; it should be confirmed by histologic examination.

Correlation of cytologic and histologic features in variants of papillary carcinoma of the thyroid.

Different morphologic variants have been described for papillary carcinoma of the thyroid, but little emphasis has been placed on their cytologic patterns. We studied fine needle aspiration (FNA) smears and histologic sections from 48 cases of papillary carcinoma, including 24 of the usual type, 13 of the follicular variant, 7 of the encapsulated variant and 4 of the tall cell variant, in an attempt to correlate the cytologic features and the different histologic variants. Single cells, monolayers and papillary fragments were present in all the variants. The presence of follicles was not restricted to the follicular variant. Nuclear grooves and cytoplasmic pseudoinclusions were present in most of the cases, with nuclear grooves the most common finding in all the variants (92.3-100%). Psammoma bodies were an infrequent finding (0-25%) and were absent from the follicular variant. Colloid was present in all the variants and was a frequent finding in the follicular variant (84.6%). The findings suggest that the exact histologic variant of papillary carcinoma cannot be predicted from the appearance of the fine needle aspirate.