Feokromasitoma
Özet
Feokromositoma, adrenal medullanın kromaffin hücrelerinden köken alan ve epizodik katekolamin salınımı nedeniyle dirençli hipertansiyon, baş ağrısı, çarpıntı ve terleme gibi paroksismal ataklara yol açan nadir bir nöroendokrin neoplazidir. Vakaların yaklaşık %90'ı tek taraflı ve benign karakterdeyken, %10'u ailesel sendromlarla (VHL, MEN 2, NF1 ve SDH mutasyonları) ilişkili, ekstra-adrenal (paraganglioma) veya malign seyirlidir. Tanısında plazma serbest metanefrin düzeyi ve 24 saatlik idrar testleri yüksek duyarlılığa sahipken, tümör lokalizasyonu için bilgisayarlı tomografi ve manyetik rezonans görüntülemeden yararlanılır. Makroskobik olarak düzgün sınırlı, kapsülsüz olan bu tümörler, mikroskobik olarak tipik "zellballen" (alveoler) patern gösterir ve immünohistokimyasal olarak sinaptofizin ve kromogranin A ile kuvvetli pozitif boyanma sergiler. Malignite potansiyelini ve metastaz riskini öngörmek amacıyla histopatolojik parametrelere dayanan PASS, GAPP ve COPPS gibi çeşitli skorlama sistemleri ile WHO tarafından TNM evrelemesi önerilmektedir. Tümörün genetik profili, özellikle SDHB mutasyonları, büyük tümör boyutu ve ekstra-adrenal yerleşim metastaz riskini ve lokal rekürrensi doğrudan artırarak prognozu olumsuz etkilemektedir.
Pheochromocytoma is a rare neuroendocrine neoplasm originating from the chromaffin cells of the adrenal medulla, leading to paroxysmal attacks such as resistant hypertension, headache, palpitation, and sweating due to episodic catecholamine release. While approximately 90% of cases are unilateral and benign, 10% are associated with familial syndromes (VHL, MEN 2, NF1, and SDH mutations), extra-adrenal (paraganglioma), or malignant. In its diagnosis, plasma free metanephrine levels and 24-hour urine tests have high sensitivity, whereas computed tomography and magnetic resonance imaging are utilized for tumor localization. Macroscopically well-circumscribed and unencapsulated, these tumors microscopically display a typical "zellballen" (alveolar) pattern and exhibit strong positive immunohistochemical staining with synaptophysin and chromogranin A. To predict malignant potential and metastatic risk, various scoring systems based on histopathological parameters, such as PASS, GAPP, and COPPS, alongside TNM staging, are recommended by the WHO. The genetic profile of the tumor, particularly SDHB mutations, large tumor size, and extra-adrenal localization, directly increases the risk of metastasis and local recurrence, thereby adversely affecting the prognosis.
Referanslar
Fung MM, Viveros OH, O'Connor DT. Diseases of the adrenal medulla. Acta physiologica. 2008;192(2): 325-335. doi:10.1111/j.1748-1716.2007.01809.x
Mete O, Asa SL, Gill AJ, et al. Overview of the 2022 WHO Classification of Paragangliomas and Pheochromocytomas. Endocrine Pathology. 2022 Mar;33(1): 90-114. doi:10.1007/s12022-022-09704-6.
O’Connor, DT. The adrenal medulla, catecholamines, and phaeochromocytoma. Cecil, RL., Goldman, L., Ausiello, DA., (ed.). Cecil’s Textbook of Medicine. Philadelphia, PA: Saunders; 2003. p. 1419-1424.
Opocher G, Schiavi F, Iacobone M, et al. Familial nonsyndromic pheochromocytoma. Annals of the New York Academy of Sciences. 2006 Aug;1073: 149-55. doi:10.1196/annals.1353.015
Fishbein L, Nathanson KL. Pheochromocytoma and paraganglioma: understanding the complexities of the genetic background. Cancer Genetics. 2012 Jan-Feb;205(1-2): 1-11. doi:10.1016/j.cancergen.2012.01.009.
Guerin C, Romanet P, Taieb D, et al. Looking beyond the thyroid: advances in the understanding of pheochromocytoma and hyperparathyroidism phenotypes in MEN2 and of non-MEN2 familial forms. Endocrine-related cancer. 2018 Feb;25(2): T15-T28. doi:10.1530/ERC-17-0266.
Amar L, Bertherat J, Baudin E, et al. Genetic testing in pheochromocytoma or functional paraganglioma. J Clin Oncol. 2005 Dec 1;23(34): 8812-8. doi:10.1200/JCO.2005.03.1484.
Turchini J, Cheung VKY, Tischler AS, et al. Pathology and genetics of phaeochromocytoma and paraganglioma. Histopathology. 2018 Jan;72(1): 97-105. doi:10.1111/his.13402.
Baguet JP, Hammer L, Mazzuco TL, et al. Circumstances of discovery of phaeochromocytoma: a retrospective study of 41 consecutive patients. European Journal of Endocrinology. 2004 May;150(5): 681-6. doi:10.1530/eje.0.1500681.
Sawka AM, Jaeschke R, Singh RJ, et al. A comparison of biochemical tests for pheochromocytoma: measurement of fractionated plasma metanephrines compared with the combination of 24-hour urinary metanephrines and catecholamines. The Journal of Clinical Endocrinology & Metabolism. 2003 Feb;88(2): 553-8. doi:10.1210/jc.2002-021251.
Grossrubatscher E, Dalino P, Vignati F, et al. The role of chromogranin A in the management of patients with phaeochromocytoma. Clinical endocrinology. 2006 Sep;65(3): 287-93. doi:10.1111/j.1365-2265.2006.02591.x.
Pacak K, Eisenhofer G, Ahlman H, et al. Pheochromocytoma: recommendations for clinical practice from the First International Symposium. Nature clinical practice Endocrinology & metabolism. 2007 Feb;3(2): 92-102. doi:10.1038/ncpendmet0396.
Humphrey R, Gray D, Pautler S, et al. Laparoscopic compared with open adrenalectomy for resection of pheochromocytoma: a review of 47 cases. Canadian Journal of Surgery. 2008 Aug;51(4): 276-80.
Thompson LD. Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases. The American journal of surgical pathology. 2002 May;26(5): 551-66. doi:10.1097/00000478-200205000-00002.
Hamidi O, Young WF Jr, Iñiguez-Ariza NM, et al. Malignant Pheochromocytoma and Paraganglioma: 272 Patients Over 55 Years. The Journal of Clinical Endocrinology & Metabolism. 2017 Sep 1;102(9): 3296-3305. doi:10.1210/jc.2017-00992.
Feng F, Zhu Y, Wang X, et al. Predictive factors for malignant pheochromocytoma: analysis of 136 patients. The Journal of urology. 2011 May;185(5): 1583-90. doi:10.1016/j.juro.2010.12.050.
Loeffel SC, Gillespie GY, Mirmiran SA, et al. Cellular immunolocalization of S100 protein within fixed tissue sections by monoclonal antibodies. Archives of pathology & laboratory medicine. 1985 Feb;109(2): 117-22. PMID: 2579618.
Wu D, Tischler AS, Lloyd RV, et al. Observer variation in the application of the Pheochromocytoma of the Adrenal Gland Scaled Score. The American journal of surgical pathology. 2009 Apr;33(4): 599-608. doi:10.1097/PAS.0b013e318190d12e.
Kimura N, Takayanagi R, Takizawa N, et al. Phaeochromocytoma Study Group in Japan. Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma. Endocr Relat Cancer. 2014 May 6;21(3): 405-14. doi:10.1530/ERC-13-0494.
Eisenhofer G, Tischler AS. Neuroendocrine cancer. Closing the GAPP on predicting metastases. Nature Reviews Endocrinology. 2014 Jun;10(6): 315-6. doi:10.1038/nrendo.2014.41.
Pierre C, Agopiantz M, Brunaud L, et al. COPPS, a composite score integrating pathological features, PS100 and SDHB losses, predicts the risk of metastasis and progression-free survival in pheochromocytomas/paragangliomas. Virchows Archiv : an International Journal of Pathology. 2019 Jun;474(6): 721-734. DOI:10.1007/s00428-019-02553-5.
Stenman A, Zedenius J, Juhlin CC. Over-diagnosis of potential malignant behavior in MEN 2A-associated pheochromocytomas using the PASS and GAPP algorithms. Langenbeck's archives of surgery. 2018;403(6): 785-790. doi:10.1007/s00423-018-1679-9
Ayala-Ramirez M, Feng L, Johnson MM, et al. Clinical risk factors for malignancy and overall survival in patients with pheochromocytomas and sympathetic paragangliomas: primary tumor size and primary tumor location as prognostic indicators. The Journal of Clinical Endocrinology & Metabolism. 2011 Mar;96(3): 717-25. doi:10.1210/jc.2010-1946.
Eisenhofer G, Lenders JW, Siegert G, et al. Plasma methoxytyramine: a novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status. European Journal of Cancer. 2012 Jul;48(11): 1739-49. doi:10.1016/j.ejca.2011.07.016. Epub 2011 Oct 28. PMID: 22036874; PMCID: PMC3372624.
Amar L, Baudin E, Burnichon N, et al. Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas. The Journal of Clinical Endocrinology & Metabolism. 2007 Oct;92(10): 3822-8. doi:10.1210/jc.2007-0709.
Cui Y, Ma X, Gao Y, et al. Local-Regional Recurrence of Pheochromocytoma/Paraganglioma: Characteristics, Risk Factors and Outcomes. Frontiers Endocrinology. 2021;12: 762548. doi:10.3389/fendo.2021.762548
Choi YM, Sung TY, Kim WG, et al. Clinical course and prognostic factors in patients with malignant pheochromocytoma and paraganglioma: A single institution experience. Journal of Surgical Oncology. 2015 Dec;112(8): 815-21. doi:10.1002/jso.24063.
Press D, Akyuz M, Dural C, et al. Predictors of recurrence in pheochromocytoma. Surgery. 2014 Dec;156(6): 1523-7; discussion 1527-8. doi:10.1016/j.surg.2014.08.044.
Asa SL, Ezzat S, Mete O. The diagnosis and clinical significance of paragangliomas in unusual locations. Journal of Clinical Medicine. 2018;7(9): 280.
Cunningham SC, Suh HS, Winter JM, et al. Retroperitoneal paraganglioma: single-institution experience and review of the literature. Journal of gastrointestinal surgery, 2006;10(8): 1156-1163.
Kimura N, Miura Y, Nagatsu I, et al. Catecholamine synthesizing enzymes in 70 cases of functioning and non-functioning phaeochromocytoma and extra-adrenal paraganglioma. Virchows Archiv A. 1992;421(1): 25-32.
