Malignant APUDoma (carcinoid) of the anterior mediastinum. Simplified methods of demonstrating biogenic amines in endocrine neoplasms

Endocrine neoplasms of the thymus and mediastinum are uncommon. This report describes such a carcinoma and the difficulty in determining its true nature. A simple modification of the technique for formaldehyde-fume-induced fluorescence (FIF) demonstrated biogenic amines in the cells. Electron microscopy and histochemical findings confirmed the close relationship of these neoplasms with neural-crest cells capable of amine precursor uptake and decarboxylation (APUD). The FIF technique is also a more sensitive method of detecting these tumors, since it has less of the sampling problems of electron microscopy, and the fluorescent granules are more easily seen than those stained by the usual methods. The techniques are simple enough for screening all poorly differentiated carcinomas in this area to determine a more accurate incidence figure.     

Use of monoclonal antibody 1H1, anticortactin, to distinguish normal and neoplastic smooth muscle cells: comparison with anti-alpha-smooth muscle actin and antimuscle-specific actin

In preliminary experiments, we found that 1H1, a monoclonal antibody directed against the v-src substrate cortactin, reacts with smooth muscle, myoepithelium, myofibroblasts, and macrophages in formaldehyde-fixed human tissues. To evaluate the use of this antibody as a diagnostic reagent, we tested the immunohistochemical distribution of cortactin in 61 mesenchymal neoplasms, 11 neuroectodermal neoplasms, and eight embryonal epithelial neoplasms. The results were compared with those obtained using antibodies against alpha-smooth muscle actin and muscle-specific actin on a similar set of tissues. With the exception of positive staining in rhabdomyosarcoma, in this series only tumors with smooth muscle differentiation appeared to contain cortactin (16 of 19 leiomyosarcomas, one infantile fibrosarcoma, one malignant fibrous histiocytoma). Immunoelectron microscopy localized cortactin to the actin-associated dense bodies of the microfilament network. We conclude that cortactin may be a useful adjunct to alpha-smooth muscle actin and muscle-specific actin as a marker for the study and diagnosis of smooth muscle neoplasms and related lesions.     

Primary mesenchymal tumors of the urinary bladder. A histological and immunohistochemical study of 30 cases

The light microscopic and immunohistochemical features of 30 primary mesenchymal neoplasms of the urinary bladder are reported. Half of the cases represented smooth and striated muscle tumors (five leiomyomas, seven leiomyosarcomas including epithelioid and myxoid subtypes, one rhabdomyoma, one embryonal rhabdomyosarcoma and one alveolar rhabdomyosarcoma). One third of the tumors were of fibrohistiocytic origin (one fibrous histiocytoma and eight malignant fibrous histiocytomas including fascicular and storiform, inflammatory and pleomorphic subtypes). In addition, a malignant epithelioid schwannoma, a round cell liposarcoma, two hemangiomas and two mixed mesodermal tumors were observed. The morphology of the vesical mesenchymal tumors was identical to that of their counterparts known to occur in other sites, particularly in the soft tissue. Muscle-specific actin, alpha-1-antichymotrypsin, S-100-protein and neuron-specific enolase proved to be useful and reliable immunomarkers for differential diagnosis of poorly differentiated leio- and rhabdomyosarcomas, malignant fibrous histiocytomas and malignant schwannomas. Since some tumors coexpressed several classes of intermediate filaments, diagnostic immunocytochemistry should only be used considering a larger panel of antibodies and in close correlation with the histological and cytological features of the neoplasms.     

Solitary fibrous tumor of the adrenal gland

Solitary fibrous tumors are rare neoplasms, most commonly involving the pleura, recently described in various other locations. We report a solitary fibrous tumor of the right adrenal gland in a 42-year-old woman, discovered incidentally during abdominopelvic ultrasonographic examination. Pathologic and immunohistologic features of the tumor were identical to those of other solitary fibrous tumors. Three-quarters of this unencapsulated infiltrating tumoral mass presented foci of hemorrhage and were made of small, round, epithelioid-like cells that expressed the CD34 antigen more weakly than do the typical spindle cells usually observed in solitary fibrous tumors. Despite hemorrhage and poor limitation, the tumor behaved in a innocuous manner; the mass remaining unchanged for more than 5 years before the patient agreed to surgical intervention, which was recommended because of a sudden enlargement of the mass.     

Tyrosine-rich crystals associated with oncocytic salivary gland neoplasms

OBJECTIVE: Crystalloids have been identified ultrastructurally within the epithelial cells of Warthin's tumors, but there have been no studies characterizing crystals or crystalloids in Warthin's tumors by light microscopy. The finding of abundant needle-shaped crystals in a fine-needle aspirate of a cystadenoma of the parotid prompted us to examine the prevalence of crystals and crystalloids in oncocytic salivary gland neoplasms. DESIGN: Ninety-seven oncocytic neoplasms (93 Warthin's tumors, 3 cystadenomas, and 1 oncocytoma) excised at our institution between 1950 and 1996 were examined, to identify crystals. Neoplasms with crystals were further characterized by means of a variety of histochemical stains and electron microscopy. Ninety-nine pleomorphic adenomas were similarly reviewed. RESULTS: Seven cases with crystals were identified. Five of these were Warthin's tumors, 1 was a cystadenoma, and 1 was an oncocytoma. The crystals were noted within tumor cysts but were not limited to the neoplasms. The crystals were predominantly either needle-shaped or tabular, but some cases contained mixtures of both as well as intermediate forms. They stained pink with hematoxylin-eosin, although the tabular forms also exhibited a focal yellow hue. The crystals were not discernible under polarized light. They stained a red-brown color with Millon's reagent, which indicated the presence of tyrosine. Trichrome, periodic acid-Schiff stain with diastase, alcian blue (pH 2.5), and Congo red stains were negative. Electron microscopy revealed sharply defined, elongate, electron-dense structures with periodicity, both extracellular and within epithelial cells. No crystals or crystalloids were identified in any of 99 pleomorphic adenomas reviewed. CONCLUSIONS: The findings indicate that tyrosine-rich crystals associated with several oncocytic salivary gland neoplasms are morphologically, histochemically, and ultrastructurally distinct from previously described tyrosine-rich crystalloids and collagenous crystalloids of pleomorphic adenomas. Although the crystals appear to form by the assembly of small units within epithelial cells, the exact mode of formation remains unclear.     

Sarcomas of the stomach

Sarcomas of the gastric wall, other than lymphomas, are a heterogeneous group of stromal malignant neoplasms composed of round and spindle cells. Many are malignant forms of epithelioid leiomyoma. Small cell size, high cellular density, a high rate of mitotic activity, and cellular pleomorphism are helpful clues in distinguishing malignant from benign gastric stromal tumors. Sarcomas of the stomach are aggressive, rapidly growing neoplasms. Among 44 examples metastasis occurred in three-fourths of the patients, usually within the first year after diagnosis.     

Solitary fibrous tumor of the nasal cavity and orbit

Solitary fibrous tumors (SFT) are rare spindle cell neoplasms generally associated with the serosal surface, especially the pleura. Two SFT are reported arising in the nasal cavity and orbit, occurring in a 33 year old female and a 21 year old male, respectively. The lesions lacked the characteristic features of other recognized neoplasms that occur in these regions. Immunohistochemically, the tumors cells were diffusely and strongly positive for vimentin and CD34 and some or many tumor cells expressed neuron-specific enolase and Leu-7. Ultrastructurally, the tumor cells showed no distinct features although they were suggested to be primitive mesenchymal or fibroblast-like cells. Both tumors were diploid by flow cytometry. The two patients have had benign clinical courses with limited follow-up. Our findings suggest that SFT is of mesenchymal cell origin and support another location for SFT, indicating additional evidence against mesothelial origin. SFT should be included in the differential diagnosis of spindle cell tumors arising in the nasal cavity and orbit.     

Ovarian small cell tumors: an electron microscopic review

Small cell tumors of the ovary are uncommon but represent an important group to recognize in the differential diagnosis of primary and metastatic ovarian neoplasms. In some cases the correct diagnosis cannot be confidently made on the basis of clinical setting, routine light microscopy, and immunohistochemistry, and electron microscopy may be supportive or definitive in establishing cell type. The cell type is often important in choosing optimal therapy and in predicting prognosis. The authors performed electron microscopy on a moderate number of ovarian small cell tumors and here describe and illustrate the diagnostic features of representative examples of various types. The ultrastructural features of the metastatic tumors, such as embryonal rhabdomyosarcoma, neuroblastoma, and melanoma, are identical to those of their respective primary tumors, are well known, and usually pose no problem in diagnosis. On the other hand, the ultrastructural features of some primary ovarian small cell tumors may present a more difficult differential diagnosis, because they have features that are subtle and/or in common. Exemplary of tumors in this category are diffuse adult granulosa cell tumor, endometrial stromal sarcoma, and small cell carcinomas of the hypercalcemic and pulmonary (oat cell) types. Distinguishing among them may be difficult but is possible, and electron microscopy may be a valuable supplement to the diagnostic information obtained from the clinical presentation, light microscopy, immunohistochemistry and, in some tumors, cytometric analysis of these neoplasms.     

Reactivity of antibody YU-311 in formalin-fixed, paraffin-embedded specimens of normal organs, non-hematopoietic tumors, and mast cell tumors

YU-311 is a monoclonal antibody that reacts with a human leukemia cell line resistant for cytosine arabinoside and that identifies a 92 kDa membrane protein. The reactivity of YU-311 in normal organs, various non-hematopoietic tumors and in mast cell tumors in formalin-fixed, paraffin-embedded specimens was examined using immunohistochemical methods. In normal organs, YU-311 reacted with fundic glands of the stomach, the intercalated duct of the pancreas, the distal portion and the loop of Henle of renal tubules and tissue mast cells. Benign neoplasms of various organs showed no immunoreaction with YU-311, except for mast cell tumors. Some types of malignant neoplasms were occasionally positive against YU-311, suggesting neoplasms arising from or differentiating along normal YU-311-positive counterparts. Some other types of malignancies were rarely positive for YU-311, although their normal counterparts showed no immunoreactivity with YU-311. None of the non-epithelial tumors reacted with YU-311, except for one case of malignant melanoma. In contrast, normal tissue mast cells and their related tumors, such as urticaria pigmentosa or solitary mastocytoma, were constantly positive for YU-311. None of the non-hematopoietic human tumor cell lines examined in the present study was reactive with YU-311. These findings indicate that YU-311 is a good marker of some types of tumors and mast cell tumors and that an aberrant expression of YU-311 rarely occurs.     

Sex cord-stromal and steroid cell tumors of the ovary

Gonadal cell types that derive from the coelomic epithelium (sex cords) or mesenchymal cells of the embryonic gonads include granulosa cells, theca cells, fibroblasts, Leydig cells, and Sertoli cells. Ovarian tumors of these cell types are called sex cord-stromal tumors. This group of tumors represents approximately 8% of ovarian neoplasms and affects all age groups. The more common types are granulosa cell tumors (GCTs), fibrothecomas, and Sertoli-Leydig cell tumors. Sex cord-stromal tumors are of interest partly because of their hormonal effects, which are rare for other ovarian neoplasms. These effects include estrogenic effects (pseudoprecocious puberty, endometrial bleeding, endometrial hyperplasia and carcinoma) and virilization. The variety of gross appearances of these tumors, ranging from large multicystic masses to small solid masses, would appear to preclude a specific radiologic diagnosis. However, in many patients, both clinical and radiologic clues can suggest the diagnosis, including predominantly fibrous content at ultrasound or magnetic resonance imaging (fibrothecoma), large hemorrhagic multicystic mass in a child with pseudoprecocious puberty (juvenile GCT), and associated syndromes such as Peutz-Jeghers syndrome (sex cord tumor with annular tubules) or Ollier disease and Maffucci syndrome (juvenile GCT).     

Different left ventricular relaxation parameters in isolated working rat and guinea pig hearts. Influence of preload, afterload, temperature, and isoprenaline

Six primary lung tumors with numerous multinucleated osteoclast-like giant cells (OLGCs) and no osteogenic component were evaluated histologically and immunohistochemically to examine pulmonary lesions inciting an OLGC response. The patients comprised four women and two men ranging in age from 61 to 80 years (average age, 69 years). The tumors consisted of one adenocarcinoma, two sarcomatoid carcinomas, and three giant cell variants of malignant fibrous histiocytoma. One tumor was endobronchial in location, while five were situated peripherally. Tumor diameter spanned from 1 to 6.5 cm (average, 2.7 cm). In addition to the giant cells, common characteristics included the malignant nature of the neoplasms and, in five of six cases, histologically malignant mesenchyme. This array of cases exemplifies the variability of lung lesions which may elicit an OLGC inflammatory response resulting in areas resembling the giant cell variant of malignant fibrous histiocytoma. The results of this study suggest that OLGCs occur preferentially in malignant rather than benign nonosteogenic lung tumors and that sarcomatoid regions of malignant tumors are more likely to be infiltrated by OLGCs than epithelial regions.     

Testicular "tumor" of the adrenogenital syndrome: a case report of an unusual association with myelolipoma and seminoma in cryptorchidism

BACKGROUND: Males with congenital adrenal hyperplasia may develop bilateral testicular masses in early adult life. These are not malignant and generally regress with corticosteroid therapy. The authors report a case occurring in a 44-year-old man with associated seminoma and myelolipoma in an undescended testis. METHODS: The testicular tumors were analyzed by histologic, flow cytometric, and ultrastructural techniques. RESULTS: The tumors in both testes were comprised of polygonal cells with abundant granular eosinophilic cytoplasm, occasionally with brown (lipochrome) pigment and round nuclei of various sizes with prominent nucleoli. These cells were grouped into nodules by dense and sometimes thick fibrous trabeculae in the right testis. The areas corresponding to the fibrous trabeculae in the left (intraabdominal) testis were replaced by mixture of hematopoietic (myeloid) and fatty tissue in various proportions characteristic of myelolipoma. The left testis also had a well demarcated tumor that was diagnostic of seminoma. Electron microscopy demonstrated abundant smooth endoplasmic reticulum, a moderate number of mitochondria with tubulovesicular cristae, lipid droplets, and lipofuscin granules in the polygonal cells. No Reinke's crystals were observed. The patient received corticosteroids for his adrenocorticoid deficiency and also underwent external beam irradiation to the retroperitoneum for seminoma. CONCLUSIONS: This case illustrates an unusual presentation of a testicular tumor in a patient with the adrenogenital syndrome as well as with myelolipoma and seminoma in a cryptorchid testis. The possibility of an associated neoplasm that could be potentially fatal should be considered whenever a testicular tumor of the adrenogenital syndrome continues to grow despite adequate hormonal treatment.     

Therapy with blood and blood products]

Rare musculoskeletal tumors can be difficult to diagnose by light microscopy or immunohistochemistry. Electron microscopy can be of diagnostic assistance especially if histotype specific ultrastructural features exist. In particular, electron microscopy for uncommon sarcomas such as alveolar soft part sarcoma, parachordoma, atypical Ewing's sarcoma and epithelioid sarcoma may be the diagnostic modality of choice.     

Fibromatosis in infancy and childhood: the spectrum

Fibromatoses form an interesting group of tumors occupying a midposition in the spectrum of fibrous tissue neoplasms. Within the fibromatoses subgroups there exists a variety of tumors whose clinical behavior spans the range from completely benign to locally aggressive. Four case histories are presented to illustrate this point. All four patients were initially seen with asymptomatic head or neck masses. The first had complete excision with no recurrence to date. The second underwent spontaneous regression after confirmation of diagnosis with biopsy. The third case had a very locally aggressive disease requiring three surgical resections to date, while the last case had one recurrence after the initial resection. With certain exceptions, initial wide local excision offers the best possible chance for cure.     

Role of electron microscopy in the evaluation of soft tissue neoplasms, with emphasis on spindle cell and pleomorphic tumors

The current significant role of transmission electron microscopy in the evaluation of soft tissue tumors when correlated with conventional histological and immunohistochemical studies is discussed for the following entities: myxofibrosarcoma, storiform-pleomorphic fibrosarcoma (malignant fibrous histiocytoma), and myofibrosarcoma; dermatofibrosarcoma protuberans; hemangiopericytoma; monophasic synovial sarcoma; extrarenal rhabdoid tumor; soft tissue perineurioma; and gastrointestinal stromal tumors, notably the so-called autonomic nerve variant.     

BRCA1 splice variants BRCA1a and BRCA1b associate with CBP co-activator

PURPOSE: To define the appearance of gastric stromal sarcomas at magnetic resonance (MR) imaging. MATERIALS AND METHODS: Nine patients with gastric stromal sarcoma underwent MR imaging with the following sequences: nonenhanced and gadolinium-enhanced breath-hold, T1-weighted, spoiled gradient-recalled echo (n = 9); fat-suppressed, T2-weighted, fast spin echo (n = 9); and breathing-independent, half-Fourier rapid acquisition with relaxation enhancement (n = 6). Lesion morphology, signal intensity features, and relationships to the gastric wall and surrounding organs were retrospectively evaluated. The diagnosis of gastric stromal sarcoma was histologically proved in all patients. RESULTS: The nine tumors were solitary, multilobulated, shaped irregularly, predominantly exophytic, and large (diameter range, 7-28 cm [mean, 15.8 cm]). The epicenters of all lesions were extrinsic to the stomach, and all lesions arose from the gastric cardia or body. Regions of necrosis and hemorrhage were detected in all cases. Marginal definition on MR images corresponded to histologic grade: High-grade neoplasms possessed ill-defined margins, and low-grade neoplasms demonstrated more well-defined margins. Relationships to surrounding organs depicted at MR imaging corresponded well with histopathologic findings. CONCLUSION: Gastric stromal sarcomas demonstrate characteristic MR imaging features, which correspond well with histopathologic findings. The direct multiplanar capability of MR imaging facilitates delineation of relationships of the tumors to the stomach and surrounding organs.     

Chordoma in childhood and adolescence. A clinicopathologic analysis of 12 cases

Chordoma is a distinctly uncommon neoplasm in the first two decades of life. To characterize further its clinicopathologic features in this age group, we studied 12 chordomas from six males and six females (age range, 1 month to 20 years at diagnosis), with a mean age of 6 years. Six tumors arose in the clivus, four in the cervical or thoracic vertebrae, and two in the lumbar and sacrococcygeal areas. The clinical presentations reflected the location. Histologically, six cases were classic chordomas; the remaining six had atypical or nonclassic features of a round cell or spindle cell tumor. Immunohistochemical stains for vimentin and cytokeratin were positive in all cases tested, whereas epithelial membrane antigen was detected in 11 examples, and S100 protein reactivity was noted in nine lesions. The tumors were uniformly nonreactive for glial fibrillary acidic protein and carcinoembryonic antigen. Electron microscopy in six cases demonstrated large primitive cells with attenuated cell junctions, whorls of cytoplasmic filaments, vacuoles, and glycogen aggregates. Ten children had died of tumor at intervals of 3 weeks to 4.5 years after diagnosis and treatment. Lung, lymph nodes, and other organs were the distant metastatic sites in seven cases. These findings imply that chordomas in children are more variable histologically and may pursue a more aggressive clinical course than their adult counterpart. Immunohistochemical studies are particularly helpful in the differentiation of atypical chordomas from other round and spindle cell neoplasms.     

Fine needle aspiration cytology of acinar cell carcinoma of the pancreas: a report of two cases

BACKGROUND: Fine needle aspiration in lieu of needle biopsy is widely used for the diagnosis of pancreatic neoplasms. The cytologic features of ductal carcinomas are well characterized, but the appearances of less common pancreatic neoplasms, such as acinar cell carcinoma (ACC), are not well described. CASES: We present the cytologic, histologic, immunocytochemical and ultrastructural features of two cases of ACC. The tumors occurred in a 36-year-old woman and 43-year-old man. The aspirate from one case contained neoplastic cells with smooth-contoured nuclei containing one or two prominent nucleoli. The aspirated material from the second case was necrotic, with numerous neutrophils and scattered nests of tumor cells similar to those present in the first case. Histologically, both tumors manifested solid and acinar patterns, and each contained some cells with periodic acid-Schiff-positive granules that were resistant to diastase. The neoplasms were immunochemically positive for trypsin and negative for neuroendocrine markers. Ultrastructurally, the aspirate from one case demonstrated apical microvilli, zymogenlike granules and abundant rough endoplasmic reticulum. CONCLUSION: Uncommon pancreatic neoplasms may be difficult to diagnose due to their cytologic and histologic subtleties. Supplemental studies including immunocytochemistry, cytochemistry and electron microscopy are important in facilitating their identification.     

Components of the vectorial capacity of Aedes poicilius for Wuchereria bancrofti in Sorsogon province, Philippines

Oncocytic neoplasms of the adrenal gland are rare. We describe the clinicopathologic and immunohistochemical findings of seven oncocytic adrenocortical neoplasms, five oncocytomas, and two oncocytic neoplasms of uncertain malignant potential. Three tumors were studied using electron microscopy. These neoplasms occurred in five women and two men (median age, 55 years) with no clinical evidence that the neoplasms were functional. The size of the neoplasms varied from 5.0 cm to 13.5 cm. Histologically, each neoplasm was composed exclusively of oncocytes. The oncocytomas had very low or absent mitotic activity and no evidence of necrosis. The two oncocytic neoplasms of uncertain malignant potential had increased mitotic activity and necrosis but no evidence of invasion or metastases. Nuclear atypia, either focal or generalized, was found in all neoplasms. Immunohistochemical studies performed using fixed, paraffin-embedded sections showed strong reactivity with the mitochondrial antibody mES-13 in all neoplasms. Four of five oncocytomas and one oncocytic neoplasm of uncertain malignant potential expressed keratin, predominantly keratin 18, as shown using the CAM 5.2 and AE3 antibodies. Two neuroendocrine-associated markers, neuron specific enolase and synaptophysin, were positive in seven and five neoplasms, respectively. However, all neoplasms were negative for the other neuroendocrine markers tested, including chromogranin A, tyrosine hydroxylase, and dopamine beta-hydroxylase, as well as for epithelial membrane antigen, S100, and p53. Using the MIB-1 (Ki-67) antibody, proliferative activity was increased in both oncocytic neoplasms of uncertain malignant potential. All six patients with available clinical follow-up data are alive without evidence disease, although the follow-up interval is relatively short (< 2 years) for the two patients with oncocytic neoplasms of uncertain malignant potential. We conclude that oncocytic adrenocortical neoplasms are nonfunctional tumors that can become large before they are detected by radiologic studies. The majority of neoplasms are benign and should not be misdiagnosed as carcinoma.     

Aspirin improves endothelial dysfunction in atherosclerosis

Archival paraffin-embedded tissue from 5 normal adrenal glands (including 1 from a fetus of 28 weeks' gestation), 6 cases of adrenal cortical hyperplasia, 9 cortical adenomas, 14 cortical carcinomas, and 11 pheochromocytomas were immunostained with monoclonal antibody against bcl-2. Ultrastructural localization of bcl-2 protein was also performed on selected cases. Positive immunostaining for bcl-2 was seen in all of the layers of the normal adrenal cortex, with different staining characteristics. bcl-2 expression was never observed in the normal adrenal medulla. Electron microscopic studies revealed bcl-2 to be localized predominantly to mitochondria, with a small number of labels along the nuclear envelope. Analysis of adrenal neoplasms showed expression of bcl-2 in cortical tumors, but only one positive case in pheochromocytomas. Restriction of bcl-2 expression to adrenal cortex-derived tissue versus adrenal medulla-derived tissue might prove to be helpful for the differential diagnosis between cortical and medullary tumors.