P-glycoprotein, metallothionein and NM23 protein expressions in breast carcinoma.

Cellular drug resistance and increased metastatic potential are the major obstacles in the successful treatment of cancer with chemotherapy. The aim of this study was to investigate whether the immunohistochemical expression of two proteins implicated in drug resistance (P-glycoprotein and metallothionein) and the product of the suppressor gene nm23 could be related to prognosis in breast cancer. Seventy-two patients with palpable or occult breast carcinoma, not treated with chemotherapy or endocrine therapy, were examined. Immunohistochemical methods were used to determine the expression of P-glycoprotein (PG), metallothionein (MT), nm23, as well as the estrogen receptor (ER), the p53 status, and the Ki67 index. The results were correlated with clinical and morphological features. Cytoplasmic and membrane-specific immunostainings of PG were seen exclusively in tumor cells and identified in 14 of 72 cases (19.4%). Only a statistically significant association with metastases, (p = 0.06) and recurrences (p = 0.1) was observed. MT-positive reaction was identified in the cytoplasm of the tumor cells in 47 (65.3%) cases. Statistical significance was associated with metastases (p = 0.07), but not with death or recurrences. Specific immunostaining of nm23 protein was seen only in the cytoplasm of tumor cells. A positive reaction was observed in 55 of 72 (89.3%) cases. Although a significant association between nm23 protein expression and other morphologic and immunohistochemical variables did not exist, we observed a higher morbidity in patients with the MT-positive/nm23-negative tumor phenotype. Univariate analysis for survival selected the following variables: histologic grade (p = 0.001), ER (p = 0.002), mitotic index (p = 0.005), Ki 67 index (p = 0.068), MT (p = 0.046) and PG (p = 0.085). The Cox model provided the following independent variables: histologic grade (p = 0.021) and metallothionein (p = 0.03). These data confirm the prognosis observed in patients with PG or metallothionein expression as well as the independence of these two variables. It also suggests that nm23 is not necessarily involved in the development of an invasive phenotype.

Fine needle aspiration cytology of high grade mucoepidermoid carcinoma of the thyroid. A case report.

BACKGROUND: Although mucoepidermoid carcinoma is considered a very rare, low grade thyroid neoplasm, in two patients a very rapid and aggressive outcome occurred. We describe the cytologic, histologic and immunohistochemical findings of a high grade mucoepidermoid carcinoma that evolved into an anaplastic carcinoma. CASE: A 57-year-old man was admitted with dysphagia, dysphonia and odynophagia. The patient had begun to develop symptoms over the previous two months. Ultrasound and computed tomography revealed diffuse enlargement of the thyroid gland with multiple, bilateral, palpable lymph nodes in the cervical, supraclavicular, paratracheal and retrocaval chains. The patient died four weeks after receiving the first cycle of treatment with adriamycin and cisplatin. The smears were highly cellular, with a background rich in neutrophilic, inflammatory infiltrate and necrotic debris. Two main types of tumor cell were identified: squamoid and mucus secreting. Squamoid cells were polygonal, with well-defined borders and dense cytoplasm. Nuclei varied greatly in shape and size and displayed clumped chromatin and prominent nucleoli. Mucussecreting cells were ring shaped and dispersed among the squamoid cells; they contained a large vacuole, with condensed acid and neutral mucins, that peripherally displaced the nucleus. Small and large clusters of large, polygonal cells with single or multiple bizarre nuclei and less-dense cytoplasm were also present. Histology revealed tumor cells distributed in irregular nests, with necrosis surrounded by a fibrous stroma. The predominant cells were squamoid, but dispersed mucus-secreting cells were frequently seen in the better-differentiated areas. Sparse anaplastic spindle cells were observed adjacent to the squamoid focus. Immunohistochemistry revealed a reaction positive for cytokeratin (AE3/AE1) in tumor nests and negative staining for thyroglobulin and neuroendocrine markers. CONCLUSION: Although mucoepidermoid carcinoma of the thyroid is a very rare neoplasm, its peculiar cytomorphologic features in fine needle aspiration cytology may contribute to its correct diagnosis.

Dipeptidyl aminopeptidase IV in the cytologic diagnosis of thyroid carcinoma.

Recently, the demonstration of DAP IV activity in thyroid cells aspirates has been proposed as an useful tool for the diagnosis of malignancy. We have studied the enzymatic activity of DAP IV, using the modified method of Lodja, in a series of 336 selected aspirates of the thyroid gland with the following cytologic diagnosis: 236 nodular hyperplasias, 60 follicular proliferations, eight Hashimoto's thyroiditis, eight Hürthe-cell proliferations, 20 papillary carcinomas, two anaplastic carcinomas, and two medullary carcinomas. The results were subjectively evaluated on the basis of staining intensity and extension in a minimum of 200 cells. Strong-to-moderate enzymatic activity with an extension of more than 40% of the cells were exclusively seen in follicular-cell derived carcinomas (papillary carcinoma, Hürthle-cell carcinoma, and follicular carcinoma). Medullary carcinoma, anaplastic carcinoma, and benign conditions were negative or weakly stained. Cytohistologic correlation in 88 patients operated on showed the following results: 26 nodular hyperplasia (18 nodular hyperplasia and eight follicular adenomas), 36 follicular proliferation (24 nodular hyperplasia, six, adenomas, three papillary carcinomas, three follicular carcinomas), two Hürthle-cell proliferation (one Hürthle-cell adenoma and one Hürthle-cell carcinoma), 20 papillary carcinomas, two medullary carcinomas, and two anaplastic carcinomas. DAP IV staining was moderate to strong and extensive in all malignant tumors initially diagnosed as follicular or Hürthle-cell proliferations. We conclude that DAP IV activity is present in malignant differentiated thyroid tumors of follicular cells (papillary carcinoma, follicular carcinoma, Hürthle-cell carcinoma), but it is identified neither in medullary carcinoma nor in anaplastic carcinoma. Therefore, its usefulness is restricted to the diagnosis of follicular-cell malignancies.

Hyalinizing trabecular carcinoma of the thyroid gland: report of two cases of follicular cell thyroid carcinoma with hyalinizing trabecular pattern.

Recently tumors have been reported that have an architectural pattern and cellularity similar to hyalinizing trabecular adenoma and show either parafollicular differentiation or histological findings suggestive of malignant neoplasm of the follicular cells. This study describes two cases of thyroid carcinoma of follicular cells that displayed a hylinizing trabecular pattern. The first case was a 25-year-old euthyroid woman with a cold thyroid nodule in the right lobe. On fine needle aspiration a diagnosis of papillary carcinoma was rendered. The thyroidectomy disclosed a 2-cm, firm, brown, encapsulated tumor in the right lobe. The tumor had a growth pattern and cytologic features similar to those described in hyalinizing trabecular adenoma. The differences between these neoplasms were the presence of mitotic figures, prominence of the nucleolus, capsular blood vessel invasion, and microtubule groups in the endoplasmic reticulum. The second case was a 19-year-old euthyroid woman with a cold thyroid nodule in the left lobe. A cytologic diagnosis of follicular proliferation was rendered. A 4-cm, firm, whitish, encapsulated nodule was found in the left lobectomy. The tumor cells were arranged in two clear-cut patterns: a trabecular hyalinizing pattern with a small focus of papillary growth, and a follicular pattern. These findings confirm the existence of malignant thyroid tumors with a hyalinizing trabecular pattern and illustrate the nonspecificity of this peculiar pattern, since it may also be seen in papillary carcinomas of the thyroid. The relationship between hyalinizing trabecular adenoma and papillary carcinoma of the thyroid is commented on.

Mesenchymal chondrosarcoma of the retroperitoneum. Report of a case diagnosed by fine needle aspiration biopsy with immunohistochemical, electron microscopic demonstration of S-100 protein in undifferentiated cells.

BACKGROUND: Mesenchymal chondrosarcoma (MC), first described in 1959 by Lichtenstein and Bernstein, is an uncommon tumor of the soft tissues and bone defined by the coexistence of nests of well-defined cartilaginous tissue within a proliferation of primitive mesenchymal cells. CASE: A 27-year-old, white female consulted a physician for a left lumbar mass associated with sciatica-type pain, asthenia, anorexia and weight loss. Abdominal computed tomography showed a 20-cm, retroperitoneal neoplasm that occupied the lower half of the left abdominal flank. Fine needle aspiration biopsy showed clusters of small round cells mixed with islets of mature cartilage. Immunomarking for electron microscopy, carried out with 15 nm of A protein/colloidal gold, showed specific immunoreactivity to S-100 protein in the nuclear chromatin, nucleoli, Golgi apparatus, plasma membrane and cytosol of cells with more developed organelles. CONCLUSION: The diagnosis of MC rests on recognition of the biphasic component of small, undifferentiated cells and cartilage islets. In aspirates with only undifferentiated cells, demonstration of ultrastructure-specific immunoreactivity to S-100 protein may contribute to the final diagnosis.

Diffuse tenosynovial giant cell tumor of soft tissues. Report of a case with cytologic and cytogenetic findings.

Extraarticular diffuse tenosynovial giant cell tumor is an unusual lesion the cytologic picture of which has not been discussed much in the literature. Fine needle aspiration biopsy of a nonpainful mass in the right shoulder in an 18-year-old woman revealed a highly cellular lesion consisting of polygonal cells and multinuclear giant cells with scant nuclear pleomorphism and a marked tendency toward xanthomization. Electron microscopy identified two basic cell populations among many intermediate forms: cells with scant filopodia and abundant ribosomes and cells with well-developed prolongations and numerous mitochondria, lysosomes and lipid drops. The karyotype of the tumor cells obtained from a surgically excised specimen showed a clonal population with 45, XX, t(1;2) (pter->p22::q24->pter), t(1:14)(qter->p13::q13->ter). The cytologic differential diagnosis included other tenosynovial lesions containing xanthomatous cells. Cytogenetic findings are discussed in relation to chromosomal alterations previously found in related lesions (nodular tenosynovitis and pigmented articular villonodular synovitis).

Fine needle aspiration diagnosis of aggressive giant cell tumor of bone. A case report.

Giant cell tumors of bone are neoplasms with potential local and systemic aggressiveness. A case of giant cell tumor with radiologic and histologic features suggestive of locally aggressive behavior is reported. Cytologic material was obtained by fine needle aspiration from an intraosseous tumor that destroyed the cortex and from the invaded, adjacent soft tissues. The smears from the osseous aspirate showed the typical cytologic features of giant cell tumor, whereas the invaded tissues had a prominent loss of cohesiveness between mononucleate and giant cells. In addition, mitotic figures in the mononucleate component were noticeable. The differential diagnosis based on clinical and cytologic findings is discussed.

Papillary cystic neoplasm of the pancreas with liver metastasis coexisting with thyroid papillary carcinoma.

BACKGROUND: Papillary cystic neoplasm of the pancreas is an uncommon neoplasm that usually appears to be benign or to have a very low potential for metastasis. We report a case of a patient with papillary and cystic neoplasm of the pancreas, which metastasized to the liver and concomitantly presented a stage I thyroid papillary carcinoma. CASE DESCRIPTION: The patient was a 38-year-old woman with a 12-year history of abdominal pain. She was first admitted to the hospital 3 years after symptoms began, and an exploratory laparotomy revealed a pancreatic cystic lesion that was diagnosed as a pancreatic pseudocyst, which drained by cystojejunosotomy. Nine years after onset, a stage I thyroid papillary carcinoma was excised. One-and-a-half years later, the patient was readmitted to the hospital for evaluation of a palpable abdominal mass. Abdominal computerized axial tomography disclosed a large pancreatic tumor and two nodular lesions of the liver. Papillary cystic neoplasm of the pancreas was diagnosed by cytologic, histologic, and ultrastructural studies of samples obtained directly from the pancreatic mass using fine-needle aspiration biopsy. The patient underwent palliative chemotherapy with mitomycin C, 4-epiadriamycin, and 5-fluorouracil. One year after this treatment began, a computerized axial tomography scan showed persistence of the pancreatic mass, with more prominent cystic spaces, increase in size and in number of the lesions in the liver, slight increase in the lesion of the right ovary, and a new lesion that also had solid and cystic areas in the spleen. CONCLUSION: The pathologic and clinical features of patients with papillary cystic neoplasm of the pancreas, based on tumoral extension, reveal localized tumors (88.2%), tumors with local infiltration or recurrence (6.2%), and tumors with metastasis at a distance (5.6%). Although strong similarities exist among the three groups, there are certain differences in age of presentation, previous clinical diagnosis of pseudocyst, and tumor location.

Metastatic glioblastoma multiforme in cervical lymph nodes. Report of a case with diagnosis by fine needle aspiration.

Metastatic glioblastoma multiforme is a rare event usually seen in patients with previous and repeated surgery. Fine needle aspiration from enlarged lymph nodes in a patient with cerebral glioblastoma multiforme showed a highly cellular smear with dispersed single cells and cell clusters. The cells had marked pleomorphism, hyperchromasia, coarse chromatin, prominent nucleoli and occasional intranuclear cytoplasmic inclusions. Multinucleate giant cells and marked endothelial proliferation were also seen. The diagnosis of metastatic glioblastoma multiforme was supported by immunohistochemistry, which showed many cells with thick and large cytoplasmic processes with intense immunoreactivity to glial fibrillary acid protein. The differential diagnosis with other metastatic small cell tumors is discussed.

Fine needle aspiration cytology of primary soft tissue tumors. Morphologic analysis of the most frequent types.

We reviewed 98 cases of fine needle aspiration of soft tissue tumors with histologic confirmation performed during an eight-year period and propose a working morphologic classification based on the most prominent cytologic features. Six main tumor groups are recognized: myxoid, round cells, spindle cells, pleomorphic cells, polygonal cells and well differentiated. We believe that this classification allows recognition of the most common soft tissue tumors while helping with the differential diagnosis of other neoplasia, primary or secondary, with similar morphology and a similar presentation.

Fine needle aspiration of peripheral neuroepithelioma of soft tissues.

Peripheral neuroepithelioma of soft tissue is a malignant primitive neuroectodermal tumor that appears both in children and adults and usually has a poor outcome. Fine needle aspiration on two patients with tumors in the lower limbs showed small round cells with unipolar processes and a tendency to form Homer-Wright rosettes. The cells had a round to oval nucleus with fine chromatin, up to four small, conspicuous nucleoli and vacuolated, periodic acid-Schiff-positive cytoplasm. The diagnosis was supported by electron microscopic study of the aspirate, which showed features of neuroblastic differentiation (i.e., neurosecretory granules), and by histologic, immunohistochemical and cytogenetic study of the resected tumors.

Fine needle aspiration in myxoid tumors of the soft tissues.

Myxoid tumors of soft tissues constitute a histogenetically heterogeneous group of lesions, both benign and malignant, that show an overproduction of mucopolysaccharide substances. A correlative fine needle aspiration (FNA) cytologic and histologic study was performed on 16 such cases (3 intramuscular myxomas, 2 lipoblastomas, 6 myxoid liposarcomas, 4 myxoid malignant fibrous histocytomas [MFHs] and 1 extraskeletal myxoid chondrosarcoma), with electron microscopic examination of the aspirate in 4 cases. FNA of all tumors produced a gelatinous material. Smears from all but one of the tumors had a granular myxoid background substance that stained blue to blue-red with the Diff-Quik stain; the exception was the extraskeletal myxoid chondrosarcoma, whose smears stained intensely blue-red to red. On light microscopy, only lipomatous tumors had distinctive cells with diagnostic value: the lipoblasts. Although the arrangement of lipoblasts in lipoblastomas differed somewhat from that found in myxoid liposarcomas, clinical data were important for making a definitive diagnosis. Intramuscular myxomas generally showed a low cellularity composed of fibroblastlike cells with no cytologic atypia. Myxoid MFHs were composed of fibroblastlike cells and macrophagelike cells; the elongated cells with slight-to-moderate nuclear atypia predominated in tumors of low-grade malignancy, while polygonal or round cells with one or more nuclei and marked nuclear atypia predominated in high-grade tumors. Although extraskeletal myxoid chondrosarcoma was mainly differentiated from low-grade myxoid MFH by its metachromatic matrix, ultrastructural studies showed the distinctive distended cisternae with microtubular aggregates in the extraskeletal myxoid chondrosarcoma, thus contributing to the definitive diagnosis.

Retroperitoneal ganglioneuroblastoma. Report of a case diagnosed by fine needle aspiration cytology and electron microscopy.

Fine needle aspiration performed on a large retroperitoneal mass in a 12-year-old boy showed neuroblasts in different stages of maturation intermingled with ganglion cells, leading to a cytologic diagnosis of ganglioneuroblastoma. This diagnosis was supported by electron microscopic study of the aspirate, which showed features of neuroblastic differentiation, and by histologic study of the resected tumor.

Fine needle aspiration cytology of recurrent ectopic meningioma.

Fine needle aspiration was performed on a recurrent extracranial meningioma in the left pterygomaxillary and temporal fossas in a 39-year-old woman. Cytologic and electron microscopic study of the aspirate and comparison to the previously resected specimen proved the recurrent nature of the lesion. The cytologic and ultrastructural findings in meningiomas are discussed with special consideration of the differential diagnosis in extracranial sites.

Fine needle aspiration cytology of paraganglionic tumors.

A comparative study of six paragangliomas from different locations and with different clinical behavior was performed. The fine needle aspirates in all cases were similar: abundant cells with round or oval nuclei and marked anisokaryosis with a tendency to form acini or follicular structures. Pheochromocytomas often contained binucleated cells and had cells with prominent intranuclear cytoplasmic inclusions more often than did other paraganglionic tumors. Similar features were seen in the excised tumors. Evaluation of the significance of nuclear variations with morphometry confirmed the subjective impression that nuclear pleomorphism is not an indicator of the biologic behavior of these lesions; paradoxically, malignant paragangliomas show less anisokaryosis than do their benign counterparts.