Loss of succinate dehydrogenase B immunohistochemical expression distinguishes pulmonary chondromas from hamartomas.

AIMS: Pulmonary chondromas, which are rare cartilaginous neoplasms that often arise in the setting of Carney triad, are morphologically similar to pulmonary hamartomas, which are much more common. There is evidence that succinate dehydrogenase (SDH) deficiency drives neoplasia in patients with Carney triad, and SDHB immunohistochemistry can be used as a surrogate marker to detect SDH deficiency. The aim of this study was to investigate the utility of SDHB immunohistochemistry in distinguishing pulmonary chondromas from hamartomas. METHODS AND RESULTS: Immunohistochemistry for SDHB (clone 21A11AE7) was performed on histological sections from six cases of pulmonary chondroma and 33 cases of pulmonary hamartoma. SDHB expression was retained in all 33 pulmonary hamartomas, and lost in the majority of evaluable chondromas (five of six). Of the five patients with chondromas showing SDHB loss, four had definitive Carney triad. Most patients with pulmonary hamartomas were older males with small solitary masses, whereas chondromas often presented as multiple masses in young females. CONCLUSION: Loss of SDHB immunohistochemical expression can be useful for differentiating pulmonary chondromas from hamartomas, and potentially identifying patients with Carney triad.

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Paragangliomas.

Updated editions of The World Health Organization Classification of Tumours Pathology & Genetics for both Head and Neck Tumours and Tumours of Endocrine Organs took place in 2016 based on consensus conferences. These editions present unification of concepts in paragangliomas and highlight expanding knowledge of their etiology. There is a major emphasis in the new bluebooks on familial/syndromic paragangliomas, representing ~40% of all head and neck paragangliomas. Ancillary use of immunohistochemical evaluation, specifically of SDHB, allows the pathologist to screen for a large subset of these potentially hereditary cases. In addition, similarly to other neuroendocrine tumors, paragangliomas are now considered to represent a continuum of risk, and are assessed in terms of risk stratification. Tumors with SDHB mutations pose the highest risk for metastasis. There is currently no validated or endorsed histologic grading system. Paragangliomas remain tumors of undetermined biologic potential and should not be termed benign.

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.

Paraganglioma retroperitoneal no funcional: reporte de un caso en la Fundación Cardioinfantil, Bogotá, Colombia / Retroperitoneal non-functional paraganglioma: report of a case from the Cardioinfantil Foundation, Bogotá, Colombia

Los paragangliomas son tumores derivados de las células cromafines de la cresta neural y por ello tienen la capacidad de secretar catecolaminas, hormonas y péptidos; al ser tumores extraadrenales del sistema nervioso central se los puede encontrar en la base del cráneo, el cuello, el tórax y el abdomen; se clasifican en funcionales y no funcionales. En este artículo se describe un paciente de sexo masculino que cursó inicialmente con dolor inespecífico en el hipocondrio derecho; con base en los estudios imaginológicos iniciales se sospechó la presencia de un neuroblastoma, pero no fue posible diferenciarlo de un paraganglioma, un ganglioneuroblastoma o un neurofibroblastoma. Se lo intervino quirúrgicamente y el estudio patológico del espécimen reveló áreas hemorrágicas extensas, compatibles con un paraganglioma extraadrenal no funcional. Estos tumores son infrecuentes, de localización diversa y de tratamiento quirúrgico difícil.

Paragangliomas are tumors derived from chromaffin cells from the neural crest. They are able to secrete catecholamines, hormones and peptides. They can be found in the skull base, neck, thorax and abdomen, and may be functional or not-functional. We report the case of a male patient with non-specific pain in the right hypochondrium. Based on the initial imaginological studies a neuroblastoma was suspected, but it not possible to differentiate it from a paraganglioma, a ganglioneuroblastoma or a neurofibroblastoma. The pathological study of the surgical specimen revealed extensive hemorrhagic areas, consistent with a non-functional extra-adrenal paraganglioma. This is an infrequent neoplasia with difficult surgical treatment.

[Gastrointestinal stromal tumor (GIST): advances in 2013]. / Gastrointestinální stromální tumor (GIST): pokroky do roku 2013.

Gastrointestinal stromal tumors (GIST) are currently regarded as a heterogenous group of tumors sharing common histological appearance, KIT immunopositivity and supposed origin from tissue progenitor cells capable of differentiation into the phenotype of Cajal interstitial cells. GISTs can be divided according to immunoexpression of the beta subunit of mitochondrial enzyme succinate dehydrogenase (SDHB) to SDHB-positive (encompassing KIT, PDGFRA and NF1 mutated GISTs), and SDHB-deficient GISTs (including Carney-Stratakis syndrome, Carney triad, sporadic pediatric GISTs, and a small subset of sporadic adult GISTs). The individual molecular subtypes differ in biological behavior and in their response to systemic targeted therapy, which is indicated in metastatic GISTs or in tumors with high risk of recurrence. Although several risk-stratification classifications have been developed, strictly defined criteria to identify patients at risk are still lacking. Pharmacogenomics have been successful in designing drugs to overcome not only the primary resistance of GISTs to the action of imatinib (e.g. GISTs with a substitution of Asp842Val in exon 18 PDGFRA or SDHB-deficient GISTs), but also the secondary resistance caused by secondary mutation of a gene encoding either the receptor tyrosine kinase or other molecules involved in the respective signalling cascade. Future directions concentrate on rational molecular targeting for systemic therapy based on complex genetic investigation of the tumor. Peripheral blood is planned to be used as a source of information for genetic events responsible for the secondary resistance of metastatic tumors.

Management of head and neck paragangliomas: a series of 9 cases and review of the literature.

We conducted a retrospective study of the long-term functional results of surgery for head and neck paragangliomas. Our study population was made up of 9 patients--4 men and 5 women, aged 22 to 59 years (mean: 46.6; median: 51)--who had undergone surgical excision of a head and neck paraganglioma from January 2002 through December 2006 in the ENT Department at Pugliese-Ciaccio Hospital in Catanzaro, Italy. Of the 9 paragangliomas, 4 were carotid body tumors, 2 were glomus tympanicum tumors, and 3 were glomus vagale tumors. None of the cases was bilateral or hereditary. Complete tumor resection was achieved in 8 patients; in the remaining patient, a small amount of intradural residual vagus nerve paraganglioma had to be left in situ. The internal carotid artery was preserved in all 4 resections of carotid body tumors. There was only 1 case of postoperative lower cranial nerve deficits, which occurred in a patient with a carotid body tumor. Follow-up ranged from 12 to 53 months (mean: 37.2; median: 36), and no recurrences were documented. Our small sample showed that surgical treatment of head and neck paragangliomas provided excellent tumor control with low postoperative morbidity, even in patients with large tumors. A wait-and-scan policy may be more appropriate for patients at an advanced age or who are otherwise at high surgical risk, as well as for those whose tumors have recurred following radiotherapy.

Surgical management of tympanojugular paragangliomas with intradural extension, with a proposed revision of the Fisch classification.

BACKGROUND: Tympanojugular paragangliomas (TJPs) with intradural extension can be successfully treated by a single or staged procedure with low surgical morbidity. OBJECTIVES: To present the clinical findings and treatment methods used for surgically treating TJP with intradural extension, as well as to discuss the complications of treatment and the relative merits of single versus staged surgery by using a comprehensive literature review comparing objective outcome measures. STUDY DESIGN: A retrospective case review of 45 cases of TJP with intradural extension. SETTING: A quaternary skull base and neurotologic center. MATERIALS AND METHODS: The charts of 45 patients with Fisch classification class C or D TJP with intradural extension, who were operated on from April 1988 to April 2010, were analyzed. Clinical findings and preoperative lower cranial nerve (LCN) palsy as well as postoperative totality of resection, postoperative LCN palsy and complications were studied. The types, indications, and distribution of staged procedures were also analyzed. RESULTS: Out of 45 cases, 22 were C3di2. The IX and X cranial nerves were the commonest nerves affected preoperatively. Preoperative internal carotid artery management was performed in 16 cases. Twenty-nine cases had a single procedure and 16 had a staged procedure. The main indication for staged procedures was intradural extension of 2 cm or more. The infratemporal fossa approach (ITFA) type A was the main procedure in all cases. Overall, total resection was achieved in 68.8% of cases with postoperative cerebrospinal fluid leak in 4.4% cases. Postoperative House-Beckmann grade I-III facial nerve status was maintained in 80% of cases, and overall LCN preservation rate was 56.9%. There were no cases requiring tracheostomy, and 3 cases required delayed phonosurgical procedures to improve their voice. CONCLUSIONS: TJP with intradural extension can be successfully managed with the judicious use of staged procedures to reduce the incidence of postoperative cerebrospinal fluid leak. The ITFA did not cause an excessively high rate of facial nerve palsy, and the overall total resection and LCN preservation rate compares very favorably with previously published data.

Vertebral artery involvement by tympanojugular paragangliomas: management and outcomes with a proposed addition to the fisch classification.

OBJECTIVES: To present the management and outcomes of cases of tympanojugular paraganglioma (TJP) with vertebral artery (VA) involvement, and to propose the addition of the new 'V' category to the Fisch classification. MATERIALS AND METHODS: Retrospective analysis of data from a quaternary neuro-otologic and skull base referral center. We studied 230 TJP patients to identify the cases with VA involvement and present their management, surgical findings and outcome. RESULTS: Out of 230 patients, 8 patients were found to have VA involvement by TJP. The extradural artery was involved in 1 patient and the intradural VA was involved in 6 patients. The intradural and extradural VA were simultaneously involved in 1 patient. Seven of the 8 patients underwent surgery. In 2 patients, preoperative occlusion was performed (1 with balloon, 1 with coils). In 5 of these 7 patients, the tumor was successfully separated from the VA by microdissection with or without endovascular intervention. In another patient, the tumor together with the involved VA was removed. Of 7 patients who had surgery, 1 patient did not undergo endovascular intervention and had subtotal tumor removal from the VA. There were no serious complications in removing the tumor from around the VA. CONCLUSION: Although uncommon, the intradural or extradural VA can be involved by TJP. To avoid vascular accidents, the VA should be thoroughly evaluated at the planning stage. We advocate that the addition of a 'V' category would help to identify patients who need individualized VA management as part of a complete surgical evaluation.

[Histological variants of parasympathetic paragangliomas (chemodectomas) of the neck and morphological variants of their malignancy]. / Gistologicheskie varianty parasimpaticheskikh paragangliom (khemodektom) shei i morfologicheskie kriterii ikh zlokachestvennosti.

Histotopograms of 28 chemodectomas have been studied. Principal microscopic features of malignancy are as follows: structural atypia (complete in solid or fibrous variants) or partial (alveolar chemodectoma) loss of alveolarity as the most important sign of organotypia; another sign of malignancy is cell cataplasia (cell and nuclear polymorphism, change in nuclear-cytoplasmic relationship in the direction of its increase, nuclear hyperchromatism, appearance of large ungly hyperploid nuclei, mitotic activity of tumour cells in one case. Incomplete angiogenesis characteristic for malignant tumours was also detected. Invasive growth in the majority of chemodectomas in the form of partial growth through the walls of great vessels and ubiquitous growth through the walls of small vessels were present in most chemodectomas. Thus, there is a basis to claim that the chemodectomas studied are malignant tumours although they are characterized by a slow (years) growth and slow progression.

[Hormone-active paragangliomas of the base of the skull]. / Gormonal'no-aktivnye paragangliomy osnovaniia cherepa.

Biochemical examination of 15 patients with paragangliomas (PG) of the base of the skull was conducted. The content of epinephrine, and norepinephrine, dopamine, and dopa in urine and the content of serotonin and histamine in blood and tumor tissue were studied. Comparison of the biochemical findings with the vegetative symptomatology allowed 3 groups of PG to be distinguished: catecholamine-secreting, serotonin-secreting, and hormone-inactive. The group of serotonin-secreting tumors of the base of the skull has not been described in the literature. The conducted research shows that tests for biogenic amines must be performed not only for diagnostic purposes but also for prognosticating possible surgical complications.

Nonfunctioning paraganglioma of the posterior mediastinum. Case report.

A case of nonfunctioning paraganglioma of the posterior mediastinum in a 20-year-old white man is presented. The diagnosis of aorticosympathetic paraganglioma (Glenner-Grimley classification) was established by histologic examination after surgical removal of the tumor.

[Classification of angiodysplasias and vascular tumors]. / Classification des angiodysplasies et tumeurs vasculaires.

Numerous vascular dysplasiae belong to the group of genodysplasiae. Most arteriovenous dysplasiae (cirsoid, racemosum aneurysms,...) are the substratum of various regional "angiomatosis". Stenotic or ectatic arterial dysplasiae can be associated with genodysplasiae. In addition, lymphatic dysplasiae (congenital elephantiasis, etc...) also exist. Among benign tumours, angiomas are sometimes hardly distinguishable from dysplasiae. Some tumors with intermediate malignancy have an uncertain prognosis: chemodectoma, hemangiopericytoma. As for malignant vascular tumours, they fall into 3 varieties: angiosarcoma, Kaposi's sarcoma and sarcoma of vascular walls.