Hereditory Pathology
Adrenal gland

I. Adrenocortical
   A. Benign tumors - adrenal cortical adenoma
       1. Conventional type
            - Sporadic
            - Hereditary
               - Congenital adrenal hyperplasia
               - McCune-Albright syndrome (OMIM #174800)
               - Melanoma-pancreatic cancer syndrome (FAMMM) (OMIM #606719)[13]
               - Multiple endocrine neoplasia, type 1 (OMIM #131100)
            - Hereditary?
               - Carney triad: pulmonary chondroma, gastric (epithelioid) GIST and paraganglioma (OMIM 604287)[16]
       2. Variants
            - Pigmented "black", oncocytic, myxoid
       3. Miscellaneous
            - Cushing's adenoma, adrenocortical incidentaloma
       4. Unknown variant/syndrome
   B. Malignant tumors – adrenal cortical carcinoma
       1. Conventional type
          - Sporadic
          - Hereditary
             - Beckwith-Wiedemann syndrome (OMIM #130650)
             - Carney complex (OMIM #160980)
             - Congenital adrenal hyperplasia
             - Familial adenomatous polyposis (OMIM #175100)
             - Li-Fraumeni syndrome (OMIM #151623)
             - Lynch syndrome (OMIM #158320)[17]
             - Multiple endocrine neoplasia, type 1 (OMIM #131100)
        2. Variants
             - Oncocytic, myxoid, adrenal carcinosarcoma, adrenal cortical blastoma[1]
        3. Unknown variant/syndrome
   C. Adrenal cortical tumor-like lesions
        1. Adrenal cortical hyperplasia
             - Bilateral
                - Diffuse, nodular, combined diffuse and nodular, macronodular with marked adrenal enlargement,
                  incidental pigmented nodules
                - Adrenocortical hyperplasia, not otherwise specified
                  - Sporadic
                  - Hereditary
                     - Familial hyperaldosteronism type 1, 2 (OMIM #103900, OMIM %605635)
                     - Multiple endocrine neoplasia type 1 (OMIM #131100)
                     - Hereditary leiomyomatosis and renal cell cancer (OMIM #150800)[15]
                - Primary pigmented nodular adrenocortical disease (PPNAD)
                   - Carney complex (OMIM #160980)
                - ACTH-independent macronodular adrenal hyperplasia
            - Unilateral
               - Diffuse, nodular, combined diffuse and nodular, incidental pigmented nodules
        2. Unknown variant/syndrome
   D. Unknown variant/syndrome
II. Adrenomedullary
   A. Pheochromocytoma
       1. Benign pheochromocytoma
            - Sporadic
            - Hereditary
               - Familial paragangliomas, types 1, 3, 4 (OMIM #168000, OMIM#605373, OMIM#115310)
               - Melanoma-pancreatic cancer syndrome (FAMMM)(OMIM #606719)[13]
               - Multiple endocrine neoplasia, type 2A (OMIM #171400)[3][13][14]
               - Multiple endocrine neoplasia, type 2B (OMIM #162300)
               - Neurofibromatosis, type 1 (OMIM #162200)
               - von Hippel-Lindau syndrome (OMIM #193300)
            - Hereditary?
               - Carney triad: pulmonary chondroma, gastric (epithelioid) GIST and paraganglioma (OMIM 604287)[16]
       2. Malignant pheochromocytoma
       3. Composite pheochromocytoma
            - Pheochromocytoma-neuroblastoma, pheochromocytoma-ganglioneuroblastoma,
             pheochromocytoma-ganglioneuroma, pheochromocytoma-malignant schwannoma
       4. Unknown variant/syndrome
   B. Adrenal medullary tumor-like lesions
       1. Adrenal medullary hyperplasia
           - Sporadic
           - Hereditary
              - Carney complex (OMIM #160980)
              - Multiple endocrine neoplasia, type 2A (OMIM #171400)
              - Multiple endocrine neoplasia, type 2B (OMIM #162300)
       2. Unknown variant/syndrome
   C. Unknown variant/syndrome
III. Secondary
   A. Metastasis
        - Breast, lung, kidney, stomach, pancreas, ovary, colon
IV. Miscellaneous
   A. Congenital/developmental non-tumor-like lesions
   B. Adrenal enlargement
        - Infection, abscess, hemorrhage, hematoma
   C. Adrenal cyst
        - Sporadic
           - Parasitic, epithelial, endothelial, pseudocyst
        - Hereditary
           - Beckwith-Wiedemann syndrome (OMIM #130650)
   D. Sex cord-stromal tumor
         - Granulosa cell, Leydig cell
   E. Adrenal soft tissue and germ cell tumors
       1. Benign lesions
            - Myelolipoma, haemangioma, leiomyoma, cystic lymphangioma, cystic teratoma,
              schwannoma, ganglioneuroma, neurofibroma, teratoma
       2. Malignant lesions
            - Angiosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, melanoma,
              lymphoma, myofibrosarcoma, primitive neuroectodermal tumor
   F. Miscellaneous
       - Aldosteronoma, neuroblastoma, fibrous histiocytoma, adenomatoid tumor, collision tumor
   G. Unknown variant/syndrome

Did Joseph Merrick (the "Elephant Man")
suffer from MEN-1, or Proteus
Show picture.

Macro- and microscopy of PPNAD in a Carney 
complex patient[12]. Show picture.

Histological comparison of MEN2- and VHL-
pheochromocytoma; distinct
phenotypes[6]. Show picture.

Bilateral pheochromocytoma in MEN-2A[8].
Show picture.

Cystic adrenal gland in a fetus of 27 weeks
with Beckwith-Wiedemann syndrome[7].

Show picture.



1. Molberg K et al. Adrenocortical blastoma. Hum Pathol. 1992 Oct;23(10):1187-90.
2. Fletcher CDM (2000), Diagnostic Histopathology of Tumors (2nd ed.),  London: Churchill Livingstone, ISBN 0-443-0-7992-7
3. DeLellis RA, Lloyd RV, Heitz PU, Eng C (2004), World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Endocrine Organs, Lyon: IARC Press, ISBN 92-832-2416-7 Online link
4. Lack EE (2007), Tumors of the Adrenal Gland and Extra-Adrenal Paraganglia, Washington DC: ARP, ISBN 1-881041-01-8
5. Kumar V, Abbas AK, Fausto N (2005), Robbins and Cotran Pathologic Basis of Disease (7th ed.). Philadelphia: Elsevier Saunders. ISBN 0-7216-0187-1
6. Vogel TW et al. Differential expression of erythropoietin and its receptor in von hippel-lindau-associated and multiple endocrine neoplasia type 2-associated pheochromocytomas. J Clin Endocrinol Metab. 2005 Jun;90(6):3747-51. Epub 2005 Mar 15. Free full text online.
7. Adrenal macrocysts page. Accessed 10 October 2011.
8. Wikipedia image page. Bilateral phaeochromocytoma in MEN-2. Accessed 21 April 2012.
9. Scarsbrook AF et al. Multiple endocrine neoplasia: spectrum of radiologic appearances and discussion of a multitechnique imaging approach. Radiographics. 2006 Mar-Apr;26(2):433-51.
10. Houston Press. Happy Birthday Joseph Merrick. Accessed 10 October 2011.
11. Koch CA et al. Pheochromocytoma in von hippel-lindau disease: distinct histopathologic phenotype compared to pheochromocytoma in multiple endocrine neoplasia type 2. Endocr Pathol. 2002 Spring;13(1):17-27.
12. Anselmo J et al. A large family with Carney complex caused by the S147G PRKAR1A mutation shows a unique spectrum of disease including adrenocortical cancer. J Clin Endocrinol Metab. 2012 Feb;97(2):351-9. Epub 2011 Nov 23. Free full text online.
13. Personal experience of the authors.
14. Oishi S et al. Coexistence of MEN 2A and papillary thyroid carcinoma and a recurrent pheochromocytoma 23 years after surgery: report of a case and a review of the Japanese literature. Jpn J Clin Oncol. 1995 Aug;25(4):153-8.
15. Schuch B et al. Adrenal nodular hyperplasia in hereditary leiomyomatosis and renal cell cancer. J Urol. 2013 Feb;189(2):430-5.
16. Almeida MQ et al. Solid tumors associated with multiple endocrine neoplasias. Cancer Genet Cytogenet. 2010 Nov;203(1):30-6. Free full text online.
17. Raymond VM et al. Adrenocortical carcinoma is a lynch syndrome-associated cancer. J Clin Oncol. 2013 Aug 20;31(24):3012-8. Epub 2013 Jul 22.

Case categories
 » Adrenal abnormalities in Carney complex (1)
 » Adrenal cortical adenoma in Familial adenomatous polyposis (FAP) (1)
 » Adrenal cortical adenoma in unknown or suspect syndromes (3)
 » Adrenal cortical carcinoma in unknown or suspected syndromes (1)
 » Adrenal cortical hyperplasia in Complement factor H-deficiency (1)
 » Adrenal cortical hyperplasia in Multiple endocrine neoplasia, type 1 (MEN-1) (2)
 » Adrenal macronodular hyperplasia in Neurofibromatosis, type 1 (NF-1) (1)
 » Adrenal medullary hyperplasia in unknown or suspect syndromes (1)
 » Composite pheochromocytoma in unknown or suspect syndromes (1)
 » Macro- and micronodular hyperplasia in Familial hyperaldosteronism, all types (2)
 » Pheochromocytoma in Lynch syndrome (1)
 » Pheochromocytoma in Melanoma-pancreatic cancer syndrome (FAMMM) (1)
 » Pheochromocytoma in Multiple endocrine neoplasia, type 2 (MEN-2A) (2)
 » Pheochromocytoma in Neurofibromatosis, type 1 (NF-1) (2)
 » Pheochromocytoma in von Hippel-Lindau syndrome (2)
 » Primary pigmented nodular adrenocortical disease in unknown or suspect syndromes (1)