|
Adenomatoid tumors (ATs) are benign neoplasms that most commonly occur in the genital tracts of both male and females.1 Extragenital ATs are rare and have been reported in the pleura, heart, omentum, the mesentery of the small intestine, pancreas, mediastinal lymph nodes and peri-umbilical skin.1,2 AT of the adrenal gland is typically an asymptomatic neoplasm with benign behavior, which has been recently recognized as a diagnostic challenge, as it is both rare and can present in such a manner as to suggest a wide range of differential diagnoses.1,3-8 Here we report a very large AT of the left adrenal gland, which at present appears to be the largest tumor of this type that has ever been reported. It may be the first case of AT associated with a high level of plasma adrenocorticotropic hormone (ACTH).
CASE REPORT
A 46-year-old Chinese woman was admitted to our hospital because of a long history of pain in the mid-abdominal region. Magnetic resonance imaging (MRI) (Figure 1) and computed tomography (CT) (Figure 2) identified a mass of 15 cm in the left suprarenal region, which was predominantly solid with some cystic areas. Laboratory test showed an increased level of serum ACTH (256 pmol/L, normal <55 pmol/L). However, the levels of plasma catecholamines and hydrocortisone were within normal limits. Based on these findings, the preoperative differential diagnoses were made of pheochromocytoma, adrenocortical carcinoma and metastatic tumor. The intraoperative frozen section showed a “benign tumor”, and a left adrenalectomy was performed.
 view in a new window |
Figure 1. Sagittal magnetic resonance image shows a 15-cm left adrenal mass (arrow).
Figure 2. CT scan shows the mass. |
Pathologically an encapsulated mass of 16 cm × 13 cm × 5 cm was found with grayish, firm, solid tumor tissue in multiple areas with sponge-like cysts. No ipsilateral adrenal gland could be identified (Figure 3). Microscopically, the tumor had a thick fibrous capsule with focal lymphocyte infiltration. Glands and cleft-like spaces were identified to be lined by cells ranging from plump epithelioid cells with abundant cytoplasm to flat mesothelial-like cells (Figure 4). Aggregates of cells with a signet ring appearance were presented in this fibrous stroma (Figure 5).
 view in a new window |
Figure 3. Grossly the tumor was an encapsulated mass consisting predominantly of grayish, firm, solid tumor tissue with multiple areas showing sponge-like cysts. No ipsilateral adrenal gland was identified.
Figure 4. Adenomatoid tumor. Anastomosing glands and cleft-like spaces are lined by cells ranging from plump epithelioid cells with abundant cytoplasm to flat mesothelial-like cells (HE staining, original magnification ×200).
Figure 5. Adenomatoid tumor. Aggregates of cells with a signet ring appearance are present in fibrous stroma (HE staining, original magnification ×400).
Figures 6. Immunohistochemical staining. Tumor cells including epithelioid cells and flattened cells are positive for calretinin (original magnification ×400) (A), D2-40 (original magnification ×400) (B) and AE1/AE3 (original magnification ×200) (C). |
Immunohistochemical staining showed that the tumor cells were positive for calretinin (1:1, Zymed, USA) (Figure 6A), D2-40 (1:50, Dako, USA) (Figure 6B), cytokeratins (AE1/AE3) (1:200, Zymed) (Figure 6C), and EMA (1:1, Dako), but negative for CD34 (1:50, Dako) and HMB45 (1:100, Dako). Transmission electron microscopy (JEM-1400, Japan) showed long, bushy microvilli (Figure 7), intracytoplasmic tonofilaments, and intercellular desmosomes (Figure 8). These immunohistochemical and electron microscopic findings were characteristics of the mesothelium, and a diagnosis of AT was made.
 view in a new window |
Figure 7. Transmission electron microscopy showing tumor cells with elongate, bushy microvilli projecting into luminal spaces (original magnification ×15 000).
Figure 8. Transmission electron microscopy showing intercellular desmosomes (original magnification ×30 000). |
DISCUSSION
AT of the adrenal gland is extremely rare, and to date only 32 cases have been reported.1,8-14 These cases were 30 to 50 years old, and most of them were male. The size of AT ranged from 0.5 cm to 11 cm, and most of the tumors were found incidentally or by autopsy because they were asymptomatic. But the reported 6 patients were found to be associated with hypertension, even some young patients,10,11 including one patient with coexisting micronodular adrenal cortical hyperplasia in the ipsilateral adrenal gland and clinical evidence of primary aldosteronism.8 One patient presented with a high level of urinary homovanillic acid, mimicking a functional tumor of the adrenal medulla.10 In addition, adrenal AT was found incidentally in a patient with AIDS and disseminated coccidiomycosis.7 AT has also been found as a “collision” tumor with myelolipoma.11 In almost all instances the adrenal gland has been easily identified adjacent to the tumor, however no adrenal gland could be found in our patient. In only one similar case reported, the tumor was found not to be clearly originated from the adrenal gland and it was therefore defined as a suprarenal tumor.12 The present case was identified by MRI and CT, and is the largest tumor of this type (15 cm in greatest dimension) reported ever since. It is also the first case of AT occurring suprarenally in association with a high level of plasma ACTH. The relationship between adrenal AT and increased ACTH level in this case is still unclear, but it may be associated with the endocrine feedback effect from the pituitary gland. It is thus important not to confuse the elevated ACTH level with a paraneoplastic syndrome, which may occur with malignant tumors.
Although the mesothelial origin of adenomatoid tumors is well recognized, the histogenesis of AT is controversial. It has been proposed that AT arises from the mesothelium of serosal surfaces, mesothelial inclusions or pluripotent mesenchyme.7 However, adrenal glands are not associated histologically with the mesothelium, and no data are available to support the development of adrenal AT from mesothelial inclusions or cysts. The embryonic pluripotent mesenchyme, which is the ultimate progenitor of both primitive Müllerian mesenchyme and mesothelial cells, may thus be the most likely origin of extragenital AT and genital tract AT.7
There is a close embryological relationship between adrenal glands and gonads.10 The female genital tract develops from the Müllerian ducts, whereas the mesonephric ducts regress. In male embryos the mesonephric ducts transform into the ducts of the epididymis and the Müllerian ducts disappear. Thus it may be hypothesized that the male predominance of AT (male:female, 31:2) may be due to this difference in embryologic development between the male and female.10
Histologically and immunohistochemically, adrenal AT is identical to AT found in the genital tract.10 In the present study, the tumor cells were positive for D2-40 and calretinin as well as cytokeratins, but staining with CD34 and HMB45 was negative, ruling out epithelioid angiosarcoma as well as angiomyolipoma, despite histologic features which included epitheloid, flattened, and signet ring cells in the tumor.
Adrenal AT may pose a diagnostic challenge and be potentially misdiagnosed as a variety of solid and cystic tumors, including metastatic adenocarcinoma, pheochro- mocytoma, epitheloid angiosarcoma, lymphangioma, angiomyolipoma, and adrenal cortical tumor.1,4,6 However, histopathological, immunohistochemical, and ultrastructural features can distinguish AT from these tumors. The benign nature of these tumors has been confirmed by the characteristic absence of local recurrence and metastatic disease. Local resection is therefore sufficient for the treatment of these tumors.
REFERENCES
1. Isotalo PA, Nascimento AG, Trastek VF, Wold LE, Cheville JC. Extragenital adenomatoid tumor of a mediastinal lymph node. Mayo Clin Proc 2003; 78: 350-354.
2. Adem C, Schneider M, Hoang C. Pathologic quiz case: an unusual umbilical mass. Arch Pathol Lab Med 2003; 127: e303-e304.
3. Simpson PR. Adenomatoid tumor of the adrenal gland. Arch Pathol Lab Med 1990; 114: 725-727.
4. Plaut A. Hemangiomas and related lesions of the adrenal gland. Virchows Arch Pathol Anat Physiol Klin Med 1962; 335: 345-355.
5. Travis WD, Lack EE, Azumi N, Tsokos M, Norton J. Adenomatoid tumor of the adrenal gland with ultrastructural and immunohistochemical demonstration of a mesothelial origin. Arch Pathol Lab Med 1990; 114: 722-724.
6. Raaf HN, Grant LD, Santoscoy C, Levin HS, Abdul-Karim FW. Adenomatoid tumor of the adrenal gland: a report of four new cases and a review of the literature. Mod Pathol 1996; 9: 1046 -1051.
7. Angeles-Angeles A, Reyes E, Munoz-Fernandez L, Angritt P. Adenomatoid tumor of the right adrenal gland in a patient with AIDS. Endocr Pathol 1997; 8: 59-64.
8. Chung-Park M, Yang JT, McHenry CR, Khiyami A. Adenomatoid tumor of the adrenal gland with micronodular adrenal cortical hyperplasia. Hum Pathol 2003; 34: 818-821.
9. Garg K, Lee P, Rob JY, Qu Z, Troncoso P, Ayala AG. Adenomatoid tumor of the adrenal gland: a clinicopathologic study of 3 cases. Ann Diagn Pathol 2005; 9: 11-15.
10. Hamamatsu A, Arai T, Iwamoto M, Kato T, Sawabe M. Adenomatoid tumor of the adrenal gland: case report with immunohistochemical study. Pathol Int 2005; 55: 665-669.
11. Timonera ER, Paiva ME, Lopes JM, Eloy C, van der Kwast T, Asa SL. Composite adenomatoid tumor and myelolipoma of adrenal gland: report of 2 cases. Arch Pathol Lab Med 2008; 132: 265-267.
12. Evans CP, Vaccaro JA, Storrs BG, Christ PJ. Suprarenal occurrence of an adenomatoid tumor. J Urol 1998; 139: 348-349.
13. Bandier PC, Hansen A, Thorelius L. Adenomatoid tumour of the adrenal gland. Ugeskr Laeger 2009; 171: 306-308.
14. Burel-Vandenbos F, Cardot-Leccia N, Effi B, Varini JP, Saint-Paul MC, Michiels JF. An unusual tumor of the adrenal gland. Ann Pathol 2005; 25: 386-388.
|
PDF(382K)
Rapid Response |