A 51-year old woman underwent mastoidectomy with labyrinthectomy on the right for a polypoid external auditory canal mass accompanied by tinnitus and ear discharge. She was reported to have undergone mastoidectomy on the same site seven years prior to the present consult. The material from this prior surgery was not made available to us.

The submitted specimen from this surgery consisted of several dark brown irregular tissue fragments with an aggregate diameter of 4.2 centimeters. Histologic sections show tumor cells arranged in "ball-like" clusters, that are surrounded by a network of sinusoidal channels. The cells are round to oval, with round, uniform nuclei that have finely granular chromatin, and moderate amounts of eosinophilic to amphophilic cytoplasm. (Figure 1)  Mitoses, nuclear pleomorphism and hyperchromasia are not observed. Immunohistochemical studies show diffuse cytoplasmic positivity for synaptophysin and chromogranin. (Figure 2)  The S100 stain highlights a peripheral layer of cells taking up the stain around the cell clusters. (Figure 3)  Based on these features, we diagnosed the case as a paraganglioma, likely a recurrence.

Paragangliomas are neuroendocrine neoplasms that arise from paraganglia found in various anatomic locations.1 In the middle ear, they arise from paraganglia found in the adventitia of the jugular bulb - hence, the old synonym "glomus jugulare" and "glomus tympanicum." Other sites where they can develop include paraganglia of the carotid artery bifurcation ("chemodectoma"), the larynx, and the vagal trunk ("glomus vagale"). The World Health Organization has simplified the nomenclature of these tumors by calling all of them simply "paraganglioma" and specifying the site involved.1 In our case, it is likely a middle ear paraganglioma, borne out by the history, clinical picture, and the morphology. Head and neck paragangliomas occur in adults, from the 5th - 6th decade, more commonly in females, and present mostly with mass-related symptoms.2,3

The morphology of paragangliomas in all head and neck locations is similar. Hematoxylin-eosin sections show cells arranged in organoid groups ("cell-ball", "Zellballen") surrounded by a vascular network. There are two cell types encountered: the chief cells, which comprise the bulk of the cell nests and have abundant eosinophilic cytoplasm, and the sustentacular cells, which are spindly and located at the periphery of the nests. Neuroendocrine immunohistochemical stains (e.g. synaptophysin, chromogranin, CD56) highlight the chief cells, while S100 and glial fibrillary acidic protein (GFAP) highlight the sustentacular cells. Cytokeratin is typically non-reactive and distinguishes this tumor from neuroendocrine tumors (i.e. carcinoid, neuroendocrine carcinoma), and middle ear adenoma.1,3 There are no consistent histologic features that can discriminate between benign and malignant cases, nor are there criteria that can predict aggressive behavior and metastasis.1,2,3

Head and neck paragangliomas are slow-growing tumors, and surgery is the most common treatment option. Radiotherapy is an option, especially for vagal paragangliomas where severe vagal nerve deficits occur in surgically treated cases.1 Recurrence after surgery is reported to be less than 10% for carotid, and up to 17% in laryngeal cases.1 Metastasis on the other hand occur in 4 - 6 % of carotid, 2% of middle ear and laryngeal, and 16% of vagal tumors.3 The World Health Organization nomenclature states that "all paragangliomas have some potential for metastasis (albeit variable)."1 Thus, long-term follow-up may be prudent for all cases.

BACKGROUND: Making the distinction between large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) is difficult in some samples of biopsy tissues, but we have to separate LCNEC from SCLC because the two types of cancer may need different therapy and they have different prognostic implications. Thus far, there are no specific immunohistochemical markers that allow distinguishing these two kinds of tumors. METHODS: We performed an immunohistochemical analysis to study the expressions of p63, Bcl-2, and 34betaE12 and to investigate whether these 3 molecules have correlations in LCNEC and SCLC. We also evaluated the expression of the neuroendocrine markers chromogranin, synaptophysin and CD56. RESULTS: A statistical analysis was performed for p63, Bcl-2, and 34betaE12 in separate and combined panels. According to the combinations of p63, Bcl-2, and 34betaE12, there were frequent expressions of p63-/Bcl-2+ or Bcl-2+/34betaE12- in the SCLC, and there was a superior proportion of them in the SCLC rather than that in the LCNEC. The p63-/Bcl-2+ and Bcl-2+/34betaE12- antibody combinations showed higher specificities compared to any single antibody for diagnosing SCLC. CONCLUSIONS: Bcl-2 and selective p63 or 34betaE12 made up a most useful panel of markers for making the differential diagnosis of LCNEC and SCLC.
Biopsy ; Carcinoma, Neuroendocrine ; Diagnosis, Differential ; Small Cell Lung Carcinoma ; Synaptophysin

Neuroendocrine tumor (NET) of the major duodenal papilla is a rare occurrence. However, that of the minor duodenal papilla is even rarer. To date, only a few cases have been reported. Herein, we present a rare case of NETs detected at the major and minor duodenal papilla synchronously, which were successfully treated with endoscopic papillectomy without procedure-related complication. To the best of our knowledge, this is the first report of this kind in the world. Photomicrograph of the biopsy specimen stained immunohistochemically for synaptophysin showed a positive reaction of tumor cells. All resection margins were negative. Further experience with more cases will be needed to establish the exact indication of endoscopic papillectomy for duodenal papillary NETs.
Ampulla of Vater ; Biopsy ; Neuroendocrine Tumors* ; Pancreatic Ducts* ; Synaptophysin

BACKGROUND: There is confusion in the diagnosis and biological behaviors of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), because of independently proposed nomenclatures and classifications. A standardized form of pathology report is required for the proper management of patients. METHODS: We discussed the proper pathological evaluation of GEP-NET at the consensus conference of the subcommittee meeting for the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. We then verified the prognostic significance of pathological parameters from our previous nationwide collection of pathological data from 28 hospitals in Korea to determine the essential data set for a pathology report. RESULTS: Histological classification, grading (mitosis and/or Ki-67 labeling index), T staging (extent, size), lymph node metastasis, and lymphovascular and perineural invasion were significant prognostic factors and essential for the pathology report of GEP-NET, while immunostaining such as synaptophysin and chromogranin may be optional. Furthermore, the staging system, either that of the 2010 American Joint Cancer Committee (AJCC) or the European Neuroendocrine Tumor Society (ENETS), should be specified, especially for pancreatic neuroendocrine neoplasms. CONCLUSIONS: A standardized pathology report is crucial for the proper management and prediction of prognosis of patients with GEP-NET.
Consensus ; Digestive System ; Humans ; Joints ; Korea ; Lymph Nodes ; Neoplasm Metastasis ; Neuroendocrine Tumors ; Prognosis ; Synaptophysin

Merkel cell carcinoma is a rare, aggressive skin cancer that occurs most frequently in the elderly on sun-exposed areas. However, any possible cutaneous or mucosal sites may also be involved. It usually presents as a rapidly- growing, painless, single red or purple colored cutaneous papule, nodule or indurated plaque that may elude diagnosis until histopathologic examination. We report a case of an 83-year old female patient who presented with a 3 x 3.5 cm sized, skin-colored, painful nodule on the left mandibular angle area. A new red nodule had combined on the original lesion after 6 months, and showed unusual clinical manifestation. Microscopically, the tumor cells were uniform with round to oval-shaped nuclei and scanty cytoplasm, and they showed a trabecular arrangement. In immunohistochemical studies, the patient was reactive to cytokeratin-20, and focally reactive to NSE and synaptophysin.
Aged ; Aged, 80 and over ; Carcinoma, Merkel Cell* ; Cytoplasm ; Diagnosis ; Female ; Humans ; Keratin-20 ; Skin Neoplasms ; Synaptophysin

The presence and distribution of pan-neuroendocrine markers such as neuron-specific enolase (NSE), chromogranin (CG), and synaptophysin (SYP) were investigated by immunohistochemistry in 15 cases of neuroblastic tumors, including four cases of neuroblastomas, six cases of ganglioneuroblastomas, and five cases of ganglioneuromas. Three cases of normal sympathetic ganglion were used for the normal control group. NSE was observed in all cases and both in ganglion cells and in neuropils. NSE was detected not only in the majority of the neuroblasts showing signs of differentiation, but also in some poorly differentiated neuroblasts. All cases of neuroblastic tumors were positive for CG, however, some variability of staining intensity and distribution patterns were noted. CG was found mainly in differentiated neuroblasts with enlarged cytoplasm and nuclei along the periphery of the perikaria, and was also found in the perinuclear regions of some undifferentiated cells. SYP was positive in 9 of 11 cases. In all of the 9 cases, SYP was detected in some differentiating neuroblasts and differentiated neuroblasts, as well as the mature ganglion cells. However, it has scarcely stained in dot or granular pattern. Two CG-negative tumors were also negative for SYP. Our data indicate that antibodies against NSE and CG are helpful as a diagnostic aid for neuroblastic tumors.
Antibodies ; Cytoplasm ; Ganglia, Sympathetic ; Ganglion Cysts ; Ganglioneuroblastoma ; Ganglioneuroma ; Immunohistochemistry ; Neuroblastoma ; Neurons* ; Neuropil ; Phosphopyruvate Hydratase* ; Synaptophysin*

We report a rare case of a 38-year-old woman with a bronchial carcinoid tumor arising from an intralobar bronchopulmonary sequestration. The vascular supply to the sequestered left lower lobe originated from the descending thoracic aorta. A left lower lobe lobectomy was performed. The findings of the pathological examination revealed an atypical carcinoid tumor that was immunopositive for chromogranin and synaptophysin. At the 3-year follow-up examination, the patient was healthy.
Adult ; Aorta, Thoracic ; Bronchopulmonary Sequestration ; Carcinoid Tumor ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; Synaptophysin

Central neurocytoma is a rare, well-differentiated neuronal tumor and is usually located in the lateral or third ventricle of young adults. The occurrence of an intraventricular tumor with a characterisitic magnetic resonance image findings including isointense signal in T1-weighted images, the presence of a cystic component, small signal-void areas due to calcification, heterogenous and hyperintense "bubbly" appearance in T2-weighted images in a young patient should suggest preoperatively the diagnosis of central neurocytoma. The typical immunohistochemical finding, positivity for synaptophysin, is the main pathological feature. We experienced two cases of central neurocytomas with typical radiological and histopathological findings. We expect growth arrest of these cases by subtotal removal to avoid postoperative neurologic deficit followed by radiation therapy.
Diagnosis ; Humans ; Neurocytoma* ; Neurologic Manifestations ; Neurons ; Synaptophysin ; Third Ventricle ; Young Adult

PURPOSE: The aim of this study was to review our experience with neuroendocrine carcinoma (NEC) of the colon and rectum to highlight the clinical and pathological characteristics in this relatively uncommon malignancy. METHODS: From December 1995 to December 2006, 11 patients with NEC were identified from our database of 6,143 colorectal cancer patients (0.18%), which does not include carcinoid tumors. The pathology was retrospectively reviewed and the tumors were categorized as pure NEC, including well-differentiated NEC (n=3), poorly-differentiated (n=3) and mixed endocrine/exocrine tumor (n=5) on the basis of the histology and immunohistochemical findings. RESULTS: The mean age of the patients was 57 yr (range, 37 to 69 yr). The tumors were located as follows: 8 in the colon and 3 in the rectum. The diagnosis of NEC was suggested preoperatively from the tissue biopsy in 2 of 9 patients (22.2%). The tumors were advanced at the time of diagnosis, with American Joint Committee on Cancer Stage III (n=7) and Stage IV disease (n=4). Most tumors stained positive by immunohistochemistry for neuroendocrine markers, including synaptophysin (7/9, 77.8%); however, chromogranin was expressed in 4 of 9 NEC tumors (44.4%). Metastatic disease was detected at the time of diagnosis in 36.4% (4/11) of the patients. The median survival for NEC was 16 mo (3.6-67.4 mo), and for pure NEC and mixed endocrine/exocrine tumor was 4.1 mo and 23.6 mo, respectively. CONCLUSION: NEC had distinctive cytoarchitectural features and was often immunoreactive for neuroendocrine markers. Our findings showed that pure NEC had aggressive behavior and a poor prognosis.
Biopsy ; Carcinoid Tumor ; Carcinoma, Neuroendocrine ; Colon ; Colorectal Neoplasms ; Humans ; Immunohistochemistry ; Joints ; Prognosis ; Rectum ; Retrospective Studies ; Synaptophysin

Primary carcinoid tumor of the kidney is a very rare disease. Until now, only 41 cases have been reported worldwide, and nine of these arose in a horseshoe kidney. In Korea, 3 cases have been reported to date, and all of these arose in a horseshoe kidney. We present a case of primary carcinoid tumor occurring in a normal kidney of a 45 year old man. A tumor was incidentally found close to the hilum of the left kidney. Histologically, the tumor exhibited trabecular and ribbon-like pattern of cuboidal or columnar cells. Mitotic activity was rarely seen. The tumor cells were positive for synaptophysin and chromogranin A. Numerous dense-core neurosecretary granules were observed by the electron microscopic examination. To our knowledge, the present case is the first report of primary renal carcinoid tumor arising in a normal kidney in Korea.
Carcinoid Tumor* ; Chromogranin A ; Humans ; Kidney* ; Korea ; Middle Aged ; Rare Diseases ; Synaptophysin