Right Thoracoabdominal Approach for Retrocardiac Paraganglioma Resection.

Paragangliomas are rare extra-adrenal tumors of sympathetic or parasympathetic paraganglia origin; of these, mediastinal paragangliomas are 2% of all cases. We present the case of a 21-year-old woman with uncontrolled arterial hypertension who had a functioning 6.5 × 6.2-cm retrocardiac paraganglioma firmly attached to the pericardium. The patient underwent tumor resection via a right thoracoabdominal incision; this surgical approach enabled adequate exposure for complete resection without institution of cardiopulmonary bypass or need for cardiac reconstruction or autotransplantation. Ten months postoperatively, the patient was doing well and was no longer hypertensive.

Soft tissue metastasis of mediastinal non-functioning paraganglioma with unusual TTF-1 expression: a potential diagnostic pitfall.

Metastatic extra-adrenal paragangliomas are very rare and can represent diagnostic challenges. We report a case of 69-year-old man with a tumor of the right shoulder. Histologic and immunohistochemical examinations confirmed the diagnosis of paraganglioma. Surprisingly, tumor cells were diffusely thyroid transcription factor 1 (TTF-1) positive. Succinate dehydrogenase complex subunit B (SDHB) deficiency has not been detected. Inherited syndromes associated with paragangliomas were ruled out. The primary tumor was identified in the mediastinum. This is the first report of TTF-1 expression in paraganglioma. To avoid misdiagnosis, careful clinical and pathological examination of any tumor with organoid growths pattern is necessary.

Pancreatic paraganglioma with draining vessels.

A pancreatic paraganglioma is a rare neoplasm that is difficult to distinguish from a pancreatic neuroendocrine tumour. Here we present a case of pancreatic paraganglioma that was surgically resected following preoperative diagnosis of a pancreatic neuroendocrine tumour. Careful evaluation of the endoscopic ultrasonography findings revealed abundant draining vessels, which could have led to a correct preoperative diagnosis of pancreatic paraganglioma.

Update on Paragangliomas and Pheochromocytomas.

Genomic studies in the recent decades lead to the identification of new genetic mutations that have been shown to play detrimental roles in the formation of pheochromocytoma or paraganglioma. The majority of these genetic mutations detected affect two major cellular pathways - pseudo hypoxic pathway and kinase signalling pathway. Genetic mutations also resulted in syndromes related to paraganglioma/pheochromocytoma. The classical syndromes comprise - neurofibromatosis, multiple neuroendocrine neoplasia (MEN) (II and III) syndromes and von Hippel-Lindau syndrome. Also, mutations in succinate dehydrogenase genes contribute to the understanding of hereditary paragangliomapheochromocytoma syndromes, Carney's triad and Carney- Stratakis syndrome. Lesions newly known to be associated with the genetic mutations in pheochromocytoma/ paraganglioma include gastrointestinal stromal tumour and renal cell carcinoma. Pathological features, proliferative index, genetic and biochemical parameters could help to predict the malignant potential of paraganglioma and pheochromocytoma. Different predictive systems have been proposed and with the help of immunochemical studies. Pathologist should be aware of the advances in knowledge and contribute to the validation of the pathological features and markers for prediction of malignant potential of this group of tumours.

(111)In-octreotide SPECT-CT in head and neck paragangliomas.

Head and neck paragangliomas are rare neuroendocrine tumors expressing somatostatin receptors on their cell surface, particularly subtype 2. Due to this distinctive feature, images can be obtained in Nuclear Medicine using synthetic analogues of somatostatin, mainly octreotide, which allow selective display by planar scintigraphy, SPECT-CT or PET-CT imaging after radiolabeling with (111)In or (68)Ga. Three cases have been selected and presented from a series of patients that illustrate the utility of SPECT-CT studies with (111)In-octreotide in the diagnosis and monitoring of this type of tumor. These are characterization at initial diagnosis, staging, and detection of local recurrence or metastasis, with added value with respect to anatomical images (nuclear magnetic resonance, computed axial tomography, angiography), for example in the differentiation between functional tissue or scar in patients who had previously undergone surgery.

Primary pancreatic paraganglioma: a report of two cases and literature review.

Paraganglioma is a rare tumor of paraganglia, derived from neural crest cells in sympathetic or parasympathetic ganglions. Primary paraganglioma originating from the pancreas is rare. We report two patients with paraganglioma in the head of the pancreas, in whom computed tomography showed a sharply marginated, hypervascular tumor with cystic areas. Significant intratumoral vessels and early contrast filling of the draining veins from the mass were not found. Although the pancreatic paraganglioma was located at the pancreatic head, the bile ducts often revealed no dilation, and sometimes the main pancreatic duct was mildly dilated. These findings are helpful in differentiating pancreatic paraganglioma from other pancreatic neoplasms. It is often difficult to distinguish between nonfunctional pancreatic paragangliomas and pancreatic endocrine tumors. In many reports,pancreatic paragangliomas show the retroperitoneal extension of a paraganglioma into the pancreas rather than a true pancreatic neoplasm. In surgical treatment, we could select simple excision of the tumor rather than radical surgery.

An unusual case of mediastinal mass and bilateral nodules.

A 23-year-old woman presented with a mediastinal paraganglioma and multiple pulmonary chondromas following antral gastric resection for gastrointestinal stromal tumor. These tumors form the Carney triad, a rare disorder of unknown genetic background. First described in 1977, approximately 120 cases have been documented in the literature. The tumors do not harbor the specific c-kit or PDGFRA gene mutations often found in sporadic gastrointestinal stromal tumor. In most cases, gastric gastrointestinal stromal tumor is the first tumor to be detected, with secondary tumors appearing years later. Even if it is rare, Carney triad should be suspected in young patients with history of gastrointestinal stromal tumor.

Malignant paraganglioma of the rectum: the first case report and a review of the literature.

Paragangliomas typically develop in the extra-adrenal sites along the sympathetic and/or the parasympathetic chain. Occasionally, the tumors may arise in some exotic sites, including the head and neck region and the urogenital tract. Paraganglioma presenting as a primary rectal neoplasm has not been well described in the literature. Here, we report the first case of malignant paraganglioma arising in the rectum of a 37-year-old male. He presented to the clinic because of hematochezia with tenesmus. The anorectal digital examination and colonoscopic examination revealed a polypoid mass of the rectum, measuring approximately 4 cm in diameter. The overall morphology and immunophenotype were consistent with a typical paraganglioma. However, the tumor exhibited features suggestive of malignant potential, including local extension into adjacent adipose tissue, nuclear pleomorphism, confluent tumor necrosis, vascular invasion and metastases to regional lymph nodes. In conclusion, we present the first case of rectal malignant paraganglioma. Due to the unexpected occurrence in this region, malignant paraganglioma may be misdiagnosed as other tumors with overlapping features; in particular, a neuroendocrine tumor of epithelial origin. Because of the differences in treatment, separating paraganglioma from its mimics is imperative. Combination of morphology with judicious immunohistochemical study is helpful in obtaining the correct diagnosis.

Gangliocytic paraganglioma of the appendix with features suggestive of malignancy, a rare case report and review of the literature.

We report a case of appendicial paraganglioma in a 40 year old female who presented with acute appendicitis and underwent laparoscopic appendectomy. To the best of our knowledge this is the first reported case of appendicial gangliocytic paraganglioma with features suggestive of malignancy in the modern literature. Van Eeden S. et al. reported the first case of appendicial paraganglioma in a 47 year old man who also presented with acute appendicitis. The appendectomy specimen showed a distended appendix with thickened wall, and a 1.3 cm mucosal based yellow lesion. Microscopically this lesion was centered in the submucosa and consisted of three different cell types: (a) epithelioid cells with pale eosinophilic finely granular cytoplasm containing bland oval nucleus with stippled chromatin, that form solid nests lying in a trabecular pattern and in formations reminiscent of 'Zellballen' as seen in paragangliomas (b) second type cells have large vesicular nuclei with prominent nucleoli and abundant cytoplasm that are scattered singly, (c) third type cells with bland elongated nuclei form broad fascicle and envelop the epithelioid and ganglion cells. Immunohistochemical analysis showed the epithelioid cell nests immunoreactive for synaptophysin and the ganglion-like cells and spindle Schwann cells to be immunoreactive for S100 protein, whereas all three cells populations were negative for CAM5.2 and Pancytokeratin. We do believe that an accurate diagnosis of Gangliocytic paraganglioma (GP) of the appendix was rendered, detailed microscopic examination of doubled hematoxylin and eosinophil stained sections as well as the immunohistochemical phenotype of the three components have been undertaken to confirm the diagnosis of GP.

Pigmented paraganglioma of the kidney: a case report.

Paragangliomas are rare neoplasms arising from undifferentiated cells of the primitive neural crest. We report a case of a 57-year-old patient with renal pigmented paraganglioma that was an incidental finding. Histopathological examination showed typical morphology of paraganglioma, as well as the unusual feature of large amounts of pigment in the cytoplasm of the tumor cells which was confirmed by bleached Fontana-Masson. Electron microscopy showed abundant, pleomorphic electron-dense granules consistent with neuromelanin. The tumor cells were positive for CD56 and chromogranin A, negative for HMB-45. The unique morphologic appearance represents divergent differentiation from neural crest. To our knowledge, the present case represents the first example of pigmented paraganglioma of the kidney. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2017147293711495.

Paratesticular paraganglioma: a rare cause of an intrascrotal mass.

We describe a case of a paratesticular paraganglioma in a 33-year-old man who presented with a scrotal mass and underwent a right testicular exploration. Metastasis is the only definite criterion for diagnosis of a malignant paraganglioma; however, lymphovascular invasion was noted in this case, which warranted a close clinical surveillance. The patient is currently well with no evidence of disease 18 months after radical orchiectomy. Paratesticular paragangliomas are extremely rare tumors with 6 cases reported in English literature. The histogenesis of these tumors is unknown. Though the histology and immunohistochemistry resemble those of paragangliomas at any other location, these tumors raise a plethora of differential diagnoses especially with the more commonly occurring tumors. Herein the relevant histopathologic differential diagnoses are discussed along with a brief review of literature.

Pulmonary meningothelial-like nodules: new insights into a common but poorly understood entity.

Although pulmonary meningothelial-like nodules (MLNs) have been recognized for decades, their nature and significance remain uncertain. This study was undertaken to evaluate MLNs in a wide range of specimens to clarify their incidence, distribution, relation to age and underlying disease, and histogenesis. Five hundred surgical lung biopsies, 25 extensively sampled lobectomies, 20 resections for pneumothoraces in persons younger than 30 years, and 92 pediatric autopsies were examined. Immunohistochemistry was performed in selected cases. One hundred eighty-six MLNs were identified in 81 cases, including 69 of 500 (13.8%) surgical biopsies and 12 of 25 (48%) lobectomies. No MLNs were found in pneumothorax resections or pediatric autopsies. Patients ranged from 22 to 84 years (mean, 62), with only 4 younger than 40 years. There were 56 women and 25 men (female:male=2.2:1). The highest incidence of MLNs was in thromboembolic disease/infarcts (5/12; 42%) and respiratory bronchiolitis-associated interstitial lung disease/desquamative interstitial pneumonia (9/35; 26%). MLNs were randomly distributed in alveolar septa with no consistent relation to small blood vessels. Immunohistochemistry demonstrated positivity for CD56 (18/18) in addition to progesterone receptor (18/18), epithelial membrane antigen (11/11), and vimentin (2/2). The high incidence of MLNs in our study may be related to underlying chronic lung disease. The finding of MLNs in almost half of extensively sampled lobectomies suggests that they may be present in all abnormal lungs if sufficiently sampled. Their absence in infants and children indicates that they are not congenital rests. The positive staining for CD56 is novel, and as CD56 has been reported in meningiomas, this finding supports meningothelial differentiation.

Histopathology and immunohistochemistry of adrenal medullary tumors and paragangliomas.

Paragangliomas arise from sympathetic or parasympathetic paraganglia and should now be defined by their site and type. The term pheochromocytoma is reserved for intra-adrenal tumors. This short review discusses the gross and microscopic features, the immunohistochemical profile, the problem of recognizing malignant potential, and the rare instances where a differential diagnosis has to be considered.

Dual CD117 expression in gastrointestinal stromal tumor (GIST) and paraganglioma of Carney triad: a case report.

Carney triad is a rare syndrome, with only 20 complete cases reported. We report a 36-year-old white woman with complete Carney triad, including metastatic gastric stromal tumor (GIST), pulmonary chondroma, and nonfunctioning extra-adrenal paraganglioma. Immunohistochemistry was positive for CD34 and CD117 (c-kit) in the GIST, and positive for chromogranin and CD117 in the paraganglioma. Ultrastructural studies demonstrated skeinoid fibers in the GIST. To our knowledge, this is the 21st complete Carney triad case reported and the first report of dual expression CD117 in both GIST and paraganglioma, a finding with intriguing pathogenetic implications related to the organization of the autonomic nervous system.

Progesterone receptor immunoreactivity in minute meningothelioid nodules of the lung.

Meningothelioid nodules (MNs) are not uncommon lesions of the pulmonary interstitium composed of monomorphic round to spindle cells, likely reactive in nature. Their origin is unsettled, though a derivation from arachnoid-like cells in conditions of perturbed perfusion of the pulmonary tissue has been proposed. Here we confirm the consistent occurrence of intense progesterone-receptor immunoreactivity in MNs fortuitously detected in surgical specimens of lung carcinomas. This finding corroborates the view that these proliferations exhibit arachnoid cell-like differentiation and suggests a role for sex-steroid hormones in the control of their growth.

Expression of angiogenic growth factors in paragangliomas.

OBJECTIVE/HYPOTHESIS: To determine if angiogenic growth factors including vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) are expressed in human paragangliomas. STUDY DESIGN: A histopathologic and molecular examination of paraganglioma specimens obtained from surgical cases or retrieved from the Pathology Department of the Massachusetts Eye and Ear Infirmary. METHODS: Fresh tumor or archival, paraffin-embedded paraganglioma specimens were analyzed by immunohistochemistry, Western blotting, and ELISA. RESULTS: Positive immunohistochemical staining for VEGF was observed in five of nine surgical specimens and in six of eight archival specimens (11/17, or 65%). PD-ECGF immunoreactivity was detected in four of five surgical specimens and six of eight archival specimens (10/13, or 77%). The presence of PD-ECGF was confirmed by Western blot assay and ELISA confirmed the presence of VEGF in tumor extract. CONCLUSIONS: Both VEGF and PD-ECGF are expressed in paragangliomas and may contribute to the extreme vascularity of these tumors. Key Words. Vascular endothelial growth factor, platelet-derived, endothelial cell growth factor, hypoxia, tumor vasculature.