The cadherin-catenin complex in laryngeal squamous cell carcinoma.

Abnormal Wnt signaling and impaired cell-cell adhesion due to abnormal E-cadherin and ß-catenin function have been implicated in many cancers, but have not been fully explored in laryngeal squamous cell carcinoma. In this study, ß-catenin cellular location and E-cadherin expression levels were analyzed in 16 laryngeal squamous cell carcinomas (LSCCs) (9 glottic and 7 supraglottic) and 11 samples of non-tumoral inflammatory larynx tissue, using immunohistochemical methods. All non-tumoral tissues showed equally strong membranous expression of ß-catenin, while cytoplasmic expression was found in only 3 of the 11 samples. By contrast, whereas 8/9 glottic LSCCs exhibited only membranous expression of ß-catenin, 6/7 supraglottic LSCCs displayed both membranous and cytoplasmic expression (p = 0.003). Strong E-cadherin staining was observed in 9/11 non-tumoral tissues and 7/9 glottic LSCCs, whereas 4/7 supraglottic LSCCs exhibited weak expression. Reduced membrane expression of E-cadherin and cytoplasmic retention of ß-catenin in supraglottic LSCC seems to be related with more aggressive biological behavior which has been described in clinical studies. Further research is required to clarify the involvement of ß-catenin in the mechanism associated with malignant transformation in laryngeal tissues.

Mitotic activity of the endocrine cells in rat thyroid glands during postnatal life.

This paper presents the results of investigations into the mitotic rates of thyroid endocrine cells in normal postnatal rats, aged 1-120 days. Our study revealed considerable age-dependent shifts in the mean mitotic activity of follicular cells and C-cells. The maximum indices of endocrine cell renewal were reached during the first 10 days of life, decreasing gradually and significantly until 25 days. At 1 month, there was a significant recuperation of the division rate for both cell types, which declined in the adult rat. These results mean that the proliferation of C-cells and follicular cells is inversely proportional to age. The preferential zone of localization of mitoses of both cell types is the central region of the thyroid lobe. The present paper provides new evidence for the postnatal origin of C-cells and follicular cells from the preexisting endocrine cells.

Yolk sac tumors with pure and mixed polyvesicular vitelline patterns.

Four cases of polyvesicular vitelline tumor are presented; two were of a previously unreported pure type, and the other two were mixed with endodermal sinus tumor. The morphologic features of the vesicles favor an endodermal origin, as originally proposed by Teilum. Marked specialization of the vesicular lining cells, seen ultrastructurally, suggests a differentiation toward gut structures and mature yolk sac. One case of pure polyvesicular vitelline tumor showed massive erythropoiesis. We propose that the pure tumor reflects an intermediate degree of differentiation within the selectively endodermal yolk sac tumor group, that is, a further stage of organization than the endodermal sinus tumor. In our cases of pure polyvesicular vitelline tumor, the marked degree of differentiaiton was correlated with an improved prognosis, as in the case of the possible homologue of this tumor, the yolk sac tumor of the infant testis. In contrast, the two cases of the tumor admixed with endodermal sinus tumor illustrated the low survival rate expected in the pure endodermal sinus tumor; in these cases the metastases had no polyvesicular component. Because of the significance of such a difference in prognosis we emphasize the importance of an accurate diagnosis, suggesting that a large number of sections be taken in order to demonstrate any endodermal sinus tumor component that may be present, and that the possibility of pure polyvesicular vitelline tumor always be considered in the differential diagnosis of multicystic ovarian tumors.

Correlation between visual clues, objective architectural features, and interobserver agreement in prostate cancer.

Three pathologists evaluated a number of designated architectural features to assign grades to 41 cases of well- to moderately differentiated adenocarcinoma, and their opinions were compared. The consensus opinion was obtained and evaluated against objective measurements of glandular architecture that were obtained by morphometric techniques. The observers agreed on gland size, gland uniformity, and the number of glands per field in only 49%, 31%, and 39% of cases, respectively. There were significant differences in the Gleason grades assigned by observers. Paired matching of individual Gleason grades showed agreement among observers in 44% (18 of 41), 56% (23 of 41), and 75% (31 of 41) of cases, respectively. This level of interobserver disagreement occurred even though cases with predominant patterns were selected carefully and those with variable patterns were excluded. A direct relationship appears to exist between increasing Gleason grade and increasing glandular variability, and there is an inverse relationship between Gleason grade, gland lumen area, and the number of glandular nuclei, as assessed by a group of pathologists.

Expression of neuropeptides and other neuroendocrine markers in human phaeochromocytomas.

AIMS: Phaeochromocytomas may produce several neuropeptides as they are considered neuroendocrine tumours. Nevertheless, studies are scarce and no clear predictive biologic value has been stablished in the case of neuropeptides expression. METHODS: We have investigated immunohistochemically the neuropeptides expression of a serie of 36 phaeochromocytomas: 25 sporadic, seven familial type MEN (multiple endocrine neoplasm) and four familial phaeochromocytomas not associated with MEN syndrome. The reactivity for neuron-specific enolase (NSE), synaptophysin, vasoactive intestinal peptide (VIP), chromogranin A, calcitonin, ACTH, somatostatin and HMB-45 was tested according to the avidin-biotin complex (ABC) method using polyclonal antibodies. RESULTS: Phaeochromocytomas have a multiple synthetic activity as main neuroendocrine feature. Despite phaeochromocytoma tumour cells heterogeneity chromogranin and synaptophysin are the most common neuropeptides synthesised, as they are associated with the presence of neuroendocrine storage granules. We find a statistically significant higher synthesis of corticotrophin hormone in familial phaeochromocytomas than in sporadic forms, on the contrary the synthesis of VIP is statistically associated with sporadic forms of phaeochromocytomas. We also found a direct relation of ACTH and overexpression and malignant tumours and a positive relationship between NSE and benign forms of phaeochromocytomas.

Blue nevus: classical types and new related entities. A differential diagnostic review.

Blue nevus is an uncommon pigmented lesion of dermal melanocytes. By convention, two well defined histologic variants, designated as "common" and "cellular", have been recognised. In the last few years, these lesions have attracted much attention due to the recognition of news entities and to its confusion with malignant melanoma. In the present review, we point out the more striking features of new related entities (combined nevus, deep penetrating nevus, compound blue nevus) and establish the differential diagnosis with conflictive lesions such as atypical blue nevus, locally aggressive blue nevus, congenital giant melanocytic nevus with nodular growth and melanocytic dermal tumor of unpredictable outcome. We also review the concept of malignant blue nevus and the significance of lymph node metastases. The blue nevus is an uncommon pigmented lesion consisting of dermal melanocytes that can appear in diverse forms: dendritic, spindle-shaped, oval-shaped, or polyhedral. Although it usually occurs in skin, it has been reported in other locations, such as oral mucosa, sclera, uterine cervix, vagina, prostate, spermatic cord, pulmonary hilus, orbit, conjunctiva, maxillary sinus, breast, and lymph nodes 3,8,42,49. Generally, it occurs in adults as a single, acquired, intensely pigmented lesion, although familial and multiple nevi have been reported 7,39. By convention, there are two well-defined histologic variants, designated as "common" and "cellular", but lesions often manifest intermediate features. In the last few years, blue nevus has attracted much attention due to the recognition of new (clinical and histologic) entities and to its confusion with malignant melanoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary vein myxoid leiomyosarcoma.

A case of myxoid leiomyosarcoma located in the right pulmonary veins is presented. The patient complained of progressive dyspnea, orthopnea, sputum cruentum and right chest pain. Angiography revealed an obliteration of right pulmonary veins by a tumor mass that expanded into the left atrium. Histologically, the lesion contained densely packed fusiform cell areas that alternated with other much less cellular and richer in interstitial myxoid matrix. The tumor cells showed specific immunoreactivity to desmin antibodies and contained abundant thin filaments with focal densities and micropinocytic vesicles.

Papillary carcinoma of the thyroid with mucoepidermoid differentiation.

A case of papillary carcinoma of the thyroid with mucoepidermoid differentiation is reported. There have been different hypotheses of the histogenesis of this tumor, one of which attributes the origin of the tumor to the ultimobranchial body, mainly because of the presence of neuroendocrine markers. In our case, no neuroendocrine immunohistochemical markers were demonstrated, but a progressive transition between follicular cells and mucinous cells with gradual loss of thyroglobulin immunoreactivity and acquisition of polyclonal carcinoembryonic antigen reactivity was noted. Therefore, we propose that mucoepidermoid carcinoma may be a simple metaplastic transformation of a papillary carcinoma, because the thyroid glandular epithelium, which is of endodermal origin, is capable of differentiating easily into squamous, mucus-secreting, or even polypeptide-secreting epithelium.

Blood group antigens in differentiated thyroid neoplasms.

Alteration of cell-surface blood group antigens during malignant transformation is a well-known phenomenon that has not yet been sufficiently investigated in thyroid gland neoplasms. We evaluated 50 normal thyroid glands and 141 differentiated thyroid neoplasms (29 follicular adenomas, 30 follicular carcinomas, 56 papillary carcinomas, and 26 medullary carcinomas) both by the immunoperoxidase technique, using monoclonal antibodies against blood group antigens (A, B, H, Le(a), Le(b), Le(x), and Le(y)) and precursor substances (T, Tn, and sTn), and by affinity to the lectin from Arachis hypogea, to determine the usefulness of these antigens as tumor markers and prognostic factors. Neoplastic tissues showed immunostaining with concordant and nonconcordant expression of ABH antigens. There were statistically significant differences between normal and neoplastic tissues but not among the different neoplasms. Statistically significant differences in Lewis antigen expression were noted between normal and neoplastic tissues and between benign and malignant tumors. Tn and sTn antigen expression showed statistically significant differences between normal and neoplastic tissues. In conclusion, blood group antigens are tumor markers that are expressed more frequently in malignant than in benign neoplasms. The presence of metastases was correlated with enhanced peanut lectin receptors and a loss of A or B antigens.

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.

Diagnostic problems in thyroid FNAs.

The use of FNA cytology to diagnose pathologic conditions of the thyroid has increased considerably in recent years, particularly since it has reduced by half the number of patients undergoing surgery. On the one hand, this diagnostic technique has attracted a certain amount of well justified criticism, but on the other, recent cytohistologic correlations and new scientific knowledge are continually improving its application. We shall discuss the latter aspect in more detail and deal with some simple but informative points which the pathologist may find useful in daily practice.

Mucinous metaplasia to neoplastic lesions in endometrial samples with cytohistologic correlation.

Seven cases of endometrial mucinous metaplasia and five of well-differentiated mucinous adenocarcinoma of the endometrium were studied. Cytologic specimens were obtained by Isaacs endometrial sampler, avoiding endocervical contamination. The histologic diagnosis between the intermediate type of mucinous metaplasia and the well-differentiated mucinous adenocarcinoma posed no problems. DNA analyses of the histologic samples showed a euploid pattern in benign and intermediate types of metaplasia, while well-differentiated mucinous adenocarcinoma showed a hyperdiploid pattern. The cytologic diagnosis of benign mucinous metaplasia should be suggested in the presence of abundant mucinous cells in endometrial samples in the absence of nuclear abnormalities.

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.

Mandibular lymphomas with sclerosis.

Two cases of non-Hodgkin's lymphoma that show a sarcomatoid pattern within the jaw are described. Their primary origin in bone was demonstrated by radiologic studies. In one case, diagnosis was delayed because the clinical picture suggested inflammatory periodontal disease. In both cases, the histologic picture was similar to that of a sarcomatoid neoplasm with intense stromal sclerosis; hemimandibulectomy was performed in one case. The tumor contained cells with large, irregular, sometimes lobulated nuclei and high mitotic activity, and perforated mandibular bone with infiltration into adjacent soft tissues. The lymphoid nature of these neoplasms was demonstrated by immunohistochemical and ultrastructural study.

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.

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.

Cytologic diagnosis of a case of recurrent adamantinoma.

The cytologic features of a case of recurrent adamantinoma of the tibia diagnosed by fine needle aspiration (FNA) in a 31-year-old patient are described. The FNA smears contained single-lying cells and cells arranged in small clusters and Indian files, with some nuclear molding. Three cell types were present: (1) large polygonal cells with chromatin clearing, (2) smaller cells with poorly defined cytoplasm and dense chromatin and (3) fusiform cells. The first two were interpreted as epithelial in nature and the third one as being derived from the stroma. These cytologic features appear to be sufficiently characteristic to suggest an FNA diagnosis of adamantinoma, especially in the case of a recurrent tumor.

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.

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.