Cercopithifilaria shohoi n. sp. (Nematoda: Filarioidea) from the relict Bovidae, Capricornis crispus, in Japan

Thirty-five chordomas and more than 100 other tumors that have to be considered in the differential diagnosis, were immunohistochemically analyzed using a panel of antibodies including those to subsets of keratins (K), HBME-1, a monoclonal antibody recognizing an unknown antigen on mesothelial cells, and neuroendocrine markers. The patterns of immunoreactivities in chordoma were compared with those in renal cell carcinoma, colorectal mucinous adenocarcinoma, pituitary adenoma, skeletal chondrosarcoma, and extraskeletal myxoid chondrosarcoma (ESMC). Chordomas were consistently positive for keratin cocktail AE1/AE3, and for the individual keratins K8 and K19, and nearly always positive for K5, but they showed negative or only sporadic reactivity for K7 and K20. The keratin K8 and K19 reactivity was retained in those chordomas showing solid sheets of epithelioid, spindle cells, or cartilaginous metaplasia, and in one of two cases showing overtly sarcomatous transformation. In comparison, keratins were never present in skeletal chondrosarcoma, although K8 and to a lesser extent K19 were seen in occasional cases of ESMC with chordoid features. HBME-1 reacted strongly with chordoma and skeletal chondrosarcoma but was almost never positive in renal or colorectal carcinoma. These carcinomas lacked K5-reactivity, in contrast to chordoma. Chordomas were also consistently positive for neuron-specific enolase and occasionally focally for synaptophysin, but never for chromogranin. In contrast, pituitary adenomas regularly expressed the full spectrum of neuroendocrine markers and differed from chordoma by having a narrower repertoire of keratins, often showing negative or focal keratin 8- or AE1/AE3 reactivity and being almost always K19-negative. These findings indicate that chordoma can be immunohistochemically separated from tumors that can resemble it. Immunohistochemistry is especially useful in the diagnosis of small biopsy specimens that offer limited material for morphological observation.     

Chordomas of the mediastinum: clinicopathologic, immunohistochemical, and ultrastructural study of six cases presenting as posterior mediastinal masses

Six cases of chordomas presenting as primary posterior mediastinal tumors are described. Three patients were female, and three were male between the ages of 8 and 65 years (mean, 40.6 years). In all cases, the tumors presented radiographically as relatively well-circumscribed, encapsulated soft tissue masses that did not seem to be related to the thoracic or dorsal spine. Only in one case, focal infiltration of bone at the level of T6-T7 was observed at the time of surgery. Histologically, the lesions showed a spectrum of features that ranged from sheets and cords of large cells with abundant vacuolated cytoplasm to small, stellate cells embedded within an abundant mucoid matrix. In one case, the cell population showed more pronounced nuclear atypia with loss of cytoplasmic vacuolization, frequent mitotic figures, necrosis, and solid areas characterized by a perivascular distribution of atypical spindle cells set against a myxoid stroma. Another case showed features of chondroid chordoma, with an immature chondroid-appearing matrix surrounding the atypical tumor cells. Immunohistochemical studies in all cases showed positive staining of the tumor cells with CAM 5.2 and broad-spectrum keratin, epithelial membrane antigen (EMA) and vimentin, and, to a lesser extent, with S-100 protein. Stains for muscle actin, carcinoembryonic antigen (CEA), and desmin were negative. Ultrastructural examination in two cases showed a spectrum of features that varied from large cells with abundant cytoplasm containing scattered ribosomes, glycogen granules, Golgi apparatti, abundant intermediate filaments, and small lumen formation with immature microvilli to smaller cells with elongated cytoplasmic processes, fewer intermediate filaments, rare desmosome type intercellular junctions, and complexes of mitochondria/rough endoplasmic reticulum. On clinical follow-up, two patients died with metastases to the lungs, chest wall, and liver from 1 to 3 years after diagnosis, and two patients are alive and well without evidence of disease after 3 and 16 years. Chordoma should be entertained in the differential diagnosis of posterior mediastinal tumors. Application of immunohistochemical stains or electron microscopy will be of aid in separating them from other conditions that may histologically closely resemble these lesions.     

Cutaneous metastasis of chordoma

A chordoma metastatic to the skin of the nose is reported. The patient (a 40-year-old man) had undergone excision of a sacral chordoma 16 months previously. In patients whose clinical histories are unknown, cutaneous metastases of chordoma can be confused with mixed tumors of sweat glands. Cytological features, including the presence of physaliphorous cells, and immunohistochemical coexpression of low molecular weight keratins and S-100 protein are helpful features that lead to a correct diagnosis.     

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.     

Low-grade myxoid chondrosarcoma of the temporal bone: differential diagnosis and report of two cases

Skull base chondrosarcoma and chordoma are rare tumors that generally have a poor prognosis. In 1973, Heffelfinger et al described a chondroid variant of chordoma, called chondroid chordoma that was found to have a significantly better prognosis than classic chordoma. However, recent evidence suggests that many of the tumors diagnosed as chondroid chordoma may, in fact, be low-grade myxoid chondrosarcomas. This report presents the diagnosis and treatment of two cases of skull base tumor that were diagnosed preoperatively as schwannoma because they were thought initially to be centred on the jugular foramen. Initial histologic evaluation suggested chondroid chordoma, but immunohistologic techniques and a review of the literature led to a diagnosis of low-grade myxoid chondrosarcoma.     

Estimation of different models of insulin therapy in noninsulin-dependent diabetes mellitus

A 21-year old woman underwent surgery in December 1996 for the removal of a presumed tuberculum sellae meningioma. However, some radio-clinical findings were proved somewhat intriguing:the patient's age, the presence of inflammatory and febrile syndromes together with the diagnosis of aseptic meningitis associated with perilesional edema intensity (an unusual feature in such cases) made us challenge the initial neuroradiological diagnosis evoked in connection with the tumoral location and dural attachment pattern. A right sub-fronto-temporal approach allowed complete tumor resection (confirmed with a postoperative MRI) and clinical recovery of the patient. But while pathological examination suggested a chordoma, the study of immunohistochemical stains revealed a meningioma. The final diagnosis was chordoid meningioma. Our review of the literature has shown that chordoid meningiomas display several areas of physaliferous cells which give the tumor a chordoma-like aspect. However, the results of immunohistochemical studies along with the location of the tumor were not consistent with the diagnosis of chordoma. Eight cases of chordoid meningiomas are reviewed in the literature. They are described as inducing systemic symptoms, particularly anemia. They could also be linked to Castleman's syndrome according to Kepes et al. After careful evaluation, we retained the hypothesis of a cause and effect relationship between the local and generalised inflammatory syndrome and chordoid meningioma.     

DNA cytophotometry and prognosis in typical and atypical bronchopulmonary carcinoids. A clinicomorphologic study of 100 neuroendocrine lung tumors

Surgical material obtained from 100 patients with typical carcinoids (TC) and atypical carcinoids (AC) of the lung (including 100 primary, four residual tumors, and four lymph node or distant metastases) was investigated by conventional histology and scanning DNA cytophotometry. Of the 60 TC (96%), 58 exhibited euploid DNA histograms compared with only 20 (50%) of the 40 AC. The morphologic findings were related to the patients' survival (median observation period, 9 years). Statistical analyses disclosed the histologic type of disease (TC versus AC) and the DNA content of tumors (euploid versus aneuploid) to affect prognosis significantly (p < 0.001). Deaths resulting from tumor were exclusively observed among patients with atypical (eight of 40) or DNA aneuploid carcinoids (eight of 22). Six patients were alive with persistent tumor manifestations 3 to 20 years after initial diagnosis, four with DNA diploid primary carcinoids. The presence of lymph node metastases alone was not associated with poor prognosis as long as the primary tumor or the related metastases showed a diploid DNA content. DNA cytophotometry thus might be regarded as an adjunctive prognostic criterion in individual carcinoid cases.     

Testicular Sertoli cell tumor with a heterologous sarcomatous component: immunohistochemical assessment of Sertoli cell differentiation

OBJECTIVE: Immunohistochemical staining is reported to be useful in distinguishing ovarian Sertoli-stromal cell tumors from carcinosarcomas. To assess Sertoli cell differentiation in a rare malignant biphasic testicular tumor, we compared the immunophenotypic profile of the tumor with that of Sertoli cell nodules and adenomas and mullerian carcinosarcomas. DESIGN: Immunohistochemical staining was performed on 6 testes (4 with hyperplastic Sertoli cell nodules, 2 with Sertoli cell adenomas) and 7 carcinosarcomas (6 involving the uterus, 1 involving the uterus and ovary) using primary monoclonal antibodies AE1/AE3, CAM 5.2, CA 19.9, and antibodies directed against epithelial membrane antigen, carcinoembryonic antigen (monoclonal and polyclonal), S100, placental alkaline phosphatase, and inhibin. These staining results were compared with those of the index case. RESULTS: All testes showed positive staining for inhibin and vimentin in the Sertoli cells of the nodules and adenomas. One Sertoli cell nodule showed focal staining with AE1/AE3 and CAM 5.2. Both adenomas showed focal positive staining for S100. All nodules and adenomas were negative for epithelial membrane antigen, monoclonal and polyclonal carcinoembryonic antigen, CA 19.9, and placental alkaline phosphatase. In contrast, the carcinomatous areas of the carcinosarcomas were all negative for inhibin but exhibited positive staining for AE1/AE3, CAM 5.2, and epithelial membrane antigen. The carcinosarcomas showed variable expression of vimentin, S100, carcinoembryonic antigen, CA 19.9, and placental alkaline phosphatase. The epithelial component of the tumor from the index case showed strong diffuse staining for inhibin and vimentin and only very faint focal staining with AE1/AE3 and CAM 5.2. The epithelial component was negative for epithelial membrane antigen, monoclonal and polyclonal carcinoembryonic antigen, S100, CA 19.9, and placental alkaline phosphatase. CONCLUSIONS: The immunohistochemical findings in the index case support the diagnosis of Sertoli cell tumor with a heterologous sarcomatous component over carcinosarcoma. Inhibin seems to be the best single marker for Sertoli cell differentiation. To our knowledge, only 1 other case of this rare testicular tumor has been reported in the literature.     

Anaplastic pleomorphic xanthoastrocytoma

Well-documented cases of malignant degeneration in pleomorphic xanthoastrocytoma and of anaplastic pleomorphic xanthoastrocytoma are rare in the literature. We report 2 cases of pleomorphic xanthoastrocytoma, 1 of which demonstrated clear evidence of malignant degeneration in the absence of prior radiation therapy over an 18-year period. Both anaplastic tumors were characterized by foci of necrosis and increased mitotic activity (3 and 2 mitotic figures/10 high-power fields). Both tumors demonstrated focal positive staining for glial fibrillary acidic protein and showed marked reticulin deposition. An MIB-1 labeling index (marker of cell proliferation) in the initial low-grade-appearing tumor in case 1 was 0.1%. The recurrent tumor in case 1 had an MIB-1 labeling index of 4.9%, and the anaplastic tumor in case 2 had an MIB-1 labeling index of 5.4%. Significant cyclin D1 immunoreactivity was not observed in either anaplastic tumor. Two percent to 3% of tumor cells stained positive with p53 protein antibody in the recurrent anaplastic tumor in case 1. Although histology may not reliably predict aggressive behavior in pleomorphic xanthoastrocytomas, the presence of increased mitosis, necrosis, and increased cell proliferation labeling indices may be indicative of a higher grade tumor.     

"Proximal-type" epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features. Clinicopathologic, immunohistochemical, and ultrastructural study of a series

Eighteen examples of an unusual malignant soft-tissue neoplasm, the morphology of which ranged from that of "atypical" epithelioid sarcoma to that of a rhabdoid tumor or undifferentiated carcinoma (with transitional forms) are described. Patients included 11 males and seven females; their median age was 35.5 years with most patients aged 20 to 40 years. Development of a mass was the main presenting symptom. Six tumors developed in the pelvis and perineal region, four in the pubic region and vulva, three in the buttocks, one in the deep soft tissues of the left hip, one on the penis, one in left forearm, one in left axilla, and one on the occiput. Tumor size ranged from 1 to 20 cm (median, 4 cm). On microscopic examination, the tumor cells invaded the subcutaneous or deep soft tissues, had prominent epithelioid or rhabdoid features, had marked cytologic atypia, and grew in a multinodular pattern in half of the cases. Areas of necrosis were often seen. A granuloma-like pattern reminiscent of that observed in classic epithelioid sarcoma was observed in only two cases. Immunohistochemically, positivity for cytokeratin, epithelial membrane antigen, and vimentin was seen in all but one of the cases. Of 16 cases, 10 and eight tumors reacted with desmin and CD34, respectively; five of 15 reacted at least focally with smooth-muscle actin, whereas three of 13 and one of 10 reacted for HMB-45 and carcinoembryonic antigen, respectively. S-100 protein and CD31 yielded negative results. Seven tumors were investigated at the ultrastructural level, four of which showed prominent intracytoplasmic intermediate filament aggregates, often accumulating into paranuclear whorls, which is in keeping with the rhabdoid phenotype. Five tumors showed features of epithelial differentiation (i.e., tonofilament-like structures or desmosomes or both), whereas one tumor displayed features of myofibroblastic differentiation. Differential diagnoses include mainly conventional epithelioid sarcoma, extrarenal malignant rhabdoid tumor, epithelioid malignant peripheral nerve sheath tumor, melanoma, rhabdomyosarcoma, and undifferentiated carcinoma. Follow-up information on 14 patients (range, 4 months to 8 years; median, 19 months) revealed local recurrence in one case and metastatic dissemination in six patients, leading to death in five. In our opinion, the above-described neoplasms represent a usually "proximal-type" of epithelioid sarcoma. In contrast to the conventional, "distal-type" epithelioid sarcoma, the proximal variant is characterized by a predominantly large-cell, epithelioid cytomorphology, marked cytologic atypia, frequent occurrence of rhabdoid features, and lack of a granuloma-like pattern in most cases. It appears to be somewhat more aggressive (or at least metastasizes earlier) than usual epithelioid sarcoma.     

Clinicopathological characteristics of prostatic adenocarcinoma in men with atypical prostate needle biopsies

PURPOSE: Atypical or nondefinitive diagnoses comprise 1.5 to 10% of all prostate needle biopsies and many men with atypical biopsy have carcinoma on rebiopsy. We characterize the clinical and pathological features of these men and the tumors, and compare them to those of other men who had more than 1 biopsy. MATERIALS AND METHODS: All prostate needle biopsies done at our institution between 1989 and 1996 on men with a followup biopsy were reviewed and the clinicopathological features were correlated. RESULTS: A total of 343 men had more than 1 biopsy during this period. Of the biopsies 64 were atypical and followup (repeat biopsy) was available for 59. Men with an atypical diagnosis were more likely to have carcinoma (34%) and to be diagnosed subsequently earlier (270 days) than those with an initial negative diagnosis (22%, 603 days). No significant differences were noted in patient age, results of digital rectal examination, initial or followup serum prostate specific antigen, subsequently identified tumor size or Gleason score on needle biopsy or at resection. Although on review as many as 38% of the original atypical foci could be reclassified, this reclassification did not significantly change the results of rebiopsy. CONCLUSIONS: Men with an atypical diagnosis on prostate biopsy are significantly more likely to have carcinoma on rebiopsy than men with an initial negative diagnosis, and the second biopsy should be performed at a significantly shorter interval. The tumors that are subsequently identified in these men are similar to those identified in men without an atypical biopsy.     

Cytogenetic analysis of aggressive meningiomas: possible diagnostic and prognostic implications

BACKGROUND: Published karyotypes from aggressive (atypical and malignant) meningiomas are few, but suggest clonal evolution from benign tumors with monosomy 22 to aggressive forms with additional abnormalities. The goal of this study was to identify the most frequent karyotypic abnormalities associated with aggressive histopathology and biologic behavior. METHODS: Eight intracranial meningiomas exhibiting histologically atypical features at the time of intraoperative diagnosis were chosen for cytogenetic analysis. The study set was comprised entirely of histologically atypical meningiomas. Four were considered malignant; three on the basis of brain invasion and one due to extracranial metastases. None was histologically anaplastic. RESULTS: Chromosomal abnormalities were demonstrated in 6 cases (75%), 5 of which were complex (63%). Loss of chromosome 22 was identified in two cases, both of which were associated with additional aberrations. Abnormalities most frequently involved chromosomes 1 (63%), 3 (50%), and 6 (63%). Four cases (50%) had dicentric or ring chromosomes. An additional 47 previously reported karyotypes from atypical and malignant meningiomas were reviewed. Comparison with published karyotypes of 200 histologically benign meningiomas served to underscore the increased frequency of complex karyotypes, chromosome 1, 3, and 6 abnormalities, and telomeric associations in the aggressive tumors. Apparently normal karyotypes as well as monosomy 22 alone were more frequently associated with benign, nonatypical histopathology. CONCLUSIONS: These findings suggest a possible role for cytogenetic analysis in determining the prognosis and perhaps in refining the diagnosis of atypical or aggressive meningiomas. Further studies are necessary to determine the significance of complex karyotypes, chromosome 1, 3, and 6 abnormalities, and telomeric associations, particularly whether they portend a more aggressive clinical course in meningiomas lacking features of histologic atypia.     

Aggressive osteoblastoma of the calcaneus

Aggressive osteoblastoma of the left calcaneus in 29-year-old Japanese woman is reported. Her initial symptom was heel pain while walking. This was a primary calcaneal tumor, initially diagnosed as a benign osteoblastoma. After a 5-year follow-up (from the initial curettage), there was local recurrence. The histologic findings of aggressive osteoblastoma were confirmed after right lower leg amputation. The recurrent tumor was mildly aggressive to the talocalcanean joint and the retrocalcaneal area, without distant metastasis. The characteristics of the primary and recurrent tumors were examined by the radiologic, histologic, and electron microscopic procedures. Although there are questions about aggressive osteoblastoma, the authors believe that there are osteoblastic tumors of borderline malignancy between benign osteoblastoma and low-grade osteosarcoma. The current case was an example compatible with an aggressive osteoblastoma with the proposed name of Dorfman classification Group 4.     

Primary renal angiosarcoma: a case report with immunohistochemical, ultrastructural, and cytogenetic features and review of the literature

Primary angiosarcoma of the kidney is a rare tumor for which fewer than 10 case reports appear in the English literature. A case of primary renal angiosarcoma is reported, in which the tumor showed poorly differentiated spindled sarcoma admixed with typical angiomatous differentiation. Antibodies against CD31, CD34, Ulex europeus lectin type I, factor VIII-related antigen, cytokeratin (AE1/AE3), vimentin, S100 protein, epithelial membrane antigen, carcinoembryonic antigen, desmin, and smooth muscle actin were examined. CD31 showed strong diffuse membranous staining of cells in the well-differentiated areas and strong membranous staining in the spindled, poorly differentiated areas. CD34 showed strong cytoplasmic and membranous staining in both the poorly differentiated and well-differentiated areas. Staining for factor VIII-related antigen and Ulex europeus was less intense and was limited to the well-differentiated areas. Staining for cytokeratin (AE1-AE3), S100, carcinoembryonic antigen, epithelial membrane antigen, desmin, and smooth muscle actin were negative. Electron microscopy showed spindle cells containing abundant pinocytotic vesicles, vimentin-type intermediate filaments, and rare Weibel-Palade bodies. A complex karyotype was found. Our findings suggest that CD31 and CD34 are useful in defining endothelial differentiation in poorly differentiated angiosarcomas in which reactions for Ulex europeus lectin type I and factor VIII-related antigen may be equivocal.     

Chordomas of the skull base. Radiologic and clinical evaluation

Chordomas are uncommon skull base tumors, which are locally agressive and are usually not amenable to complete surgical resection. Proton beam irradiation, following surgery, is the preferred treatment modality. For diagnosis and determination of tumor site and extension, CT and MR imaging are the imaging modalities of choice. CT delineates bone destruction and the presence of calcifications and destroyed bone optimally. MR imaging is the modality of choice for better definition of the tumor margin from brain and other soft tissue structures (pharynx) and visualization of blood vessels. The signal intensities and enhancement pattern fail to differentiate chordoma from chondroid chordoma or chondrosarcoma. Chordomas arise from the clivus and therefore are located more centrally, whereas the majority of chondrosarcomas originate in the petroclival fissure and occur more laterally, although occasional overlap occurs in about one third of cases. Immunohistochemical methods allow differentiation of pure chordoma from chondroid chordoma and chondrosarcoma. Chordomas have a lower local control rate than chondrosarcomas.     

Acquired umbilical fistula after repair of inguinal hernia: a case report

A 2-year, 9-month-old boy had an umbilical fistula after repair of an inguinal hernia at 8 months of age. Fistulography findings showed a duct running from the umbilicus toward the inguinal wound. Pathological finding of the surgically removed fistula demonstrated granulomatous tissues containing silk ligature. Acquired umbilical fistula is a rare complication of inguinal herniorrhaphy. Its clinical details as well as a review of the previously reported four cases are presented.     

Hemorrhagic chondroid chordoma mimicking pituitary apoplexy

We describe a hemorrhagic chondroid chordoma involving the sella turcica with suprasellar extension. The CT and MRI appearances mimiked a hemorrhagic pituitary adenoma. Chondroid chordoma is a variant composed of elements of both chordoma and cartilaginous tissue. An uncommon bone neoplasm, located almost exclusively in the spheno-occipital region, it is usually not considered in the differential diagnosis of a tumor with acute hemorrhage in the sellar region. We discuss the clinical and radiological characteristics which may allow one to differentiate chondroid chordoma from other tumors of this area.     

Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses

Small cell neuroendocrine carcinomas (SNECs) of the sinonasal tract are extremely uncommon tumors. We reviewed the clinicopathologic features of six cases of this neoplasm. There was no sex preponderance with three females and three males and a mean age at presentation of 51 years (range, 38 to 68). Two patients had disease limited to the nasal cavity, and in four the tumor involved the nasal cavity and maxillary or ethmoid sinuses. Involvement of the orbit was present in two patients. Surgery was the primary treatment. After a mean follow-up of 37 months, one patient died of local disease and liver metastases, four were alive with recurrent or metastatic disease, and one died of unrelated causes. The tumors were composed of sheets, nests, and trabeculae with extensive areas of necrosis and hemorrhage. The individual cells were small to intermediate in size and had scanty cytoplasm. The nuclei were oval or round and hyperchromatic with absent or inconspicuous nucleoli. Nuclear molding and crush artefact were present in five cases. All tumors had a high mitotic rate with frequent abnormal mitotic figures. All cases stained for Cam 5.2, neuron-specific enolase, and chromogranin. Five cases were positive for AE1:AE3, and four for synaptophysin. No case stained for S-100 protein, or neurofilaments. O-13 stained one case. No case contained EBV-RNA. SNECs of the nasal cavity and paranasal sinuses are aggressive tumors with pathological features similar to those of anaplastic small cell carcinomas of the lung. They exhibit morphological and immunophenotypic features different from olfactory neuroblastoma and should be distinguished from this tumor.     

Genotator: a workbench for sequence annotation

The clinical, pathological, and immunohistochemical features of six cases of metastatic neuroendocrine and carcinoid tumors to the thyroid simulating medullary thyroid carcinoma (MTC) are described. The patients were women between the ages of 24 and 70 years who, without symptoms or significant past medical histories, presented with either a single mass or multiple thyroid nodules. The primary source of the tumor was only discovered on follow-up. Two of the neoplasms were classical carcinoid tumors, one was a carcinoid predominantly composed of large cells, another showed a prominent oval to spindle cell component, and the two remaining cases were atypical carcinoid/high-grade neuroendocrine carcinomas. The immunohistochemical profile was inconsistent with MTC in that all tumors were negative for calcitonin and only two were focally positive for carcinoembryonic antigen (CEA). A variable pattern of staining for other neuroendocrine and epithelial markers was obtained in each case. Despite the morphologic and immunohistochemical similarities with MTC, the diagnosis of a metastatic neuroendocrine tumor to the thyroid should be favored in the presence of a predominantly interstitial pattern of spread; occurrence of multiple tumor foci; folliculotropism; rosette formations with lumen and cuticular borders; and lack of immunoreactivity for calcitonin and CEA. The differential diagnosis between MTC and metastatic neuroendocrine carcinoma to the thyroid is of importance because of the vast differences in treatment and prognosis.     

Early childhood angiofibroma in an unusual site

Angiofibromas are usually characterized by their occurrences in adolescent males with a typical localization and involvement of the posterior nasal cavity and nasopharynx. Even the suspicion of an extranasopharyngeal angiofibroma or an angiofibroma in young children must be viewed in general with skepticism, although reports of angiofibromas with atypical localizations and manifestations in young children have appeared in the literature. Three cases of this fibro-vascular neoplasm with manifestations in the first decade of life and atypical localizations are presented: (1) an angiofibroma medial to the left lacrimal sac in a 15-month old boy, (2) a right paranasal localization in a 9-year-old boy and (3) an angiofibroma limited to the right sphenoid sinus in a 6-year old boy. In all three cases the neoplasm was resected via an endonasal, micro-endoscopic approach that avoided an external incision. According to the literature and based on our own experiences with typical histological findings in all three cases, the clinician has to be aware that the rare angiofibroma can occur in preadolescent children with atypical localizations. The endonasal surgical approach is without any doubt the least traumatic one and in selected cases allows resection of a circumscribed tumor considering functional and aesthetic aspects.