Adrenal Gland

This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2021, Case 5, and is myelolipoma with sickle cell disease presenting in the adrenal gland.

The information provided in this case was accurate and correct at the time of publication in 2021.

Any changes in terminology since the time of publication may not be reflected in this case.

The sections show abundant mature adipose tissue without cytologic atypia. Interspersed throughout the adipose tissue are islands of hematopoietic precursors in various stages of maturation. Most sections contain foci of all three maturing lineages (myeloid, erythroid, and megakaryocytic). No dysplastic maturation or significant numbers of blasts are seen. ​Although usually not necessary, ​CD61 immunohistochemistry can be used to highlight the scattered megakaryocytes​. ​Myeloperoxidase and CD33 can be used to mark the myeloid cells​, while​ glycophorin and hemoglobin peroxidase ​will stain the​ erythroid cells. Many of the slides also show scattered lymphoid aggregates. The lymphocytes are small in size, with coarse chromatin and indistinct nucleoli. Overall, the histologic findings are diagnostic of myelolipoma. Close inspection of many of the slides also shows extensive sickling of red cells and marked erythrophagocytosis, which is consistent with the patient’s history of sickle cell disease.

Adrenal myelolipoma is a benign incidental tumor usually detected either by imaging studies or at the time of autopsy. They are most commonly found in the adrenal gland and are less commonly in extra adrenal sites, ​such as​​ ​the perirenal area, in the abdomen, thorax, pelvis, and bone. CT findings are usually that of a rounded, non-enhancing adrenal mass. Myelolipomas can rarely be multifocal, as in this case. Most myelolipomas are non-functioning tumors, but rare cases have been associated with congenital adrenal hyperplasia and Cushing disease. Most affected patients are asymptomatic, although large tumors can present with abdominal pain and rarely, they can rupture.

The etiology of myelolipoma is not fully understood, but different etiologies have been suggested. Myelolipomas have been reported in patients with sickle cell disease, and it has been postulated that the hematopoietic elements could represent a compensatory response to the patient’s persistent anemia. One reported case showed a t(3;21) translocation, but no recurrent molecular alterations have been described.

Accessory spleen (spleniculi) could be in the differential diagnosis, and accessory spleen can rarely involve the perirenal areas. To diagnose accessory spleen, look for ​splenic tissue (​areas of white pulp and red pulp​)​. This case shows small lymphoid aggregates, which could be misinterpreted as white pulp. Even though there are a lot of sickled red blood cells, no well-formed red pulp sinusoids are identified, and the presence of trilineage hematopoiesis in the adrenal gland is diagnostic for myelolipoma.

Myeloid sarcoma is a tumor mass consisting of myeloid blasts that occur​ ​outside of the bone marrow. Mature neutrophils may or may not be present. Typically, the tumor consists of blasts and early myeloid/monocytic precursors, though trilineage hematopoiesis can be uncommonly seen. If a myeloid sarcoma occurs in soft tissue with fat, it could be mistaken for a myelolipoma, but myelolipoma does not contain blasts. Myeloid sarcoma also lacks the circumscribed nature of myelolipoma. CD34 may be used to highlight the presence of blasts.

Lipoma can also be in the differential diagnosis of a myelolipoma, especially in cases of myelolipoma with scant amounts of extramedullary hematopoiesis and a large amount of fat. Sometimes performing additional levels or deeper sections can ​better highlight foci of​​ ​hematopoietic elements.

Angiomyolipoma can be mistaken for myelolipoma, especially when a prominent lipomatous component obscures the vascular and myoid components. Angiomyolipoma should not contain areas of trilineage hematopoiesis. Immunohistochemical positivity for HMB45 and desmin in angiomyolipoma would distinguish it from myelolipoma.

Extramedullary hematopoiesis and small myelolipomatous changes without tumor formation can occasionally be seen in adrenal glands. These cases can be associated with adenomas or adrenal cortical hyperplasia. Also, small myelolipomatous changes without tumor formation, as the name implies, should not be associated with a mass ​(​to differentiate it from a myelolipoma​)​, but can show similar histologic findings, such as trilineage hematopoiesis and fat.

​​​​​​Well-differentiated liposarcoma will also present with a fat component but should​ at least ​​​​exhibit ​​​focal cytologic atypia​ and MDM2 positive immunohistochemistry or ​MDM2​ amplification by FISH testing. Fat necrosis typically shows p​artially necrotic adipose tissue with foamy macrophages, multinucleated giant cells and chronic inflammatory cells. Similar to liposarcoma, fat necrosis usually does not contain large amounts of extramedullary hematopoiesis. Waterhouse-Friderichsen (WF) syndrome demonstrates hemorrhage and necrosis of the adrenal glands which is usually caused by a bacteremia, classically ​​Neisseria meningitidis. ​​Again, ​extramedullary​ ​hematopoiesis​ and fat are not main components of WF syndrome. ​

1. What findings would favor an accessory spleen over an adrenal myelolipoma?
   1. CD33 expression
   2. HMB45 expression
   3. Lymphoid aggregates
   4. Perirenal mass​ ​
   5. White and red pulp
2. Which of the following statements is most accurate regarding adrenal myelolipoma?
   
   
   1. CD61 can be used to highlight erythroid cells.
   2. It commonly has t(8;21) translocation.
   3. It is a malignant and aggressive tumor.
   4. It is most commonly found in the thorax.
   5. It may be seen in patients with Cushing disease.
3. WAn adrenal mass is resected, and the histologic findings show a mass containing numerous myeloid blasts as well as neutrophils and monocytes. What is the most accurate diagnosis?
   
   
   1. Accessory spleen
   2. Angiomyolipoma
   3. Extramedullary hematopoiesis
   4. Myeloid sarcoma
   5. Adrenal myelolipoma

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3. Gamss C, Chia F, Chernyak V, Rozenblit A. Giant hemorrhagic myelolipoma in a patient with sickle cell disease. Emerg Radiol. 2009;16(4):319-322.
4. Goetz SP, Niemann TH, Robinson RA, Cohen MB. Hematopoietic elements associated with adrenal glands. A study of the spectrum of change in nine cases. Arch Pathol Lab Med. 1994;118(9):895-896.
5. Papotti M, Falhammar M. Adrenal myelolipoma.In: WHO Classification of Tumours Editorial Board. Endocrine and neuroendocrine tumors [internet]. IARC Press; 2022 [cited 2023 December 26] (WHO Classification tumours series, 5th ed; vol 10). Available from https://tumourclassificatio.iarc.who.int/chapter/53 ;

1. White and red pulp (e)
2. It may be seen in patients with Cushing disease (e)
3. Myeloid sarcoma (d)