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Images in Endocrine Pathology: Unique Composite Adrenal Adenomatoid Tumor, Ganglioneuroma, Myelolipoma, and Cortical Nodular Hyperplasia
Eleonora Duregon1 · Marco Volante1 · Stefano Guzzetti2 · Ida Rapa1 . Simona Vatrano1 · Mauro Papotti1
C Springer Science+Business Media New York 2017
Case History
A 48-year-old male patient had a surgical resection of a right testis seminoma. During preoperative imaging studies, a solitary node of the left adrenal gland was found. Since the suspected preoperative diagnosis was a nonfunctioning cortical adenoma, in the absence of hormonal hyper-incretion effects, the adrenal lesion was removed 6 months after the testis surgery.
What Is It Your Diagnosis?
Histopathologic Diagnosis: Composite Adrenal Adenomatoid Tumor, Ganglioneuroma, Myelolipoma, and Cortical Nodular Hyperplasia
The adrenalectomy specimen consisted of a bilobated tumor measuring 4 cm in its maximum diameter with a pale gray and partly cream-colored, smooth cut surface. There were several cystic spaces of 0.5 to 1 cm, but neither hemorrhage nor necrosis were noted. A rim of cortical tissue at the periphery was found. After complete embedding, at light microscopy, four different morphological patterns were found (Figs. 1 and 2). The first was a well-circumscribed area (Fig. 1), composed of interweav- ing fascicles of Schwann cells, with no immature element, in a myxoid stroma containing mature ganglion cells and minimal adipose tissue (Fig. 3a, b). The other three components were
intermingled one into each other, and distinct from the former (Fig. 2). Among them, anastomosing tubules and cleft-like spaces of variable size and shape were observed, some of which arranged in multiple microcysts and separated by solid fibrous stroma. These structures were lined by a spectrum of plump epithelioid to flattened cells resembling endothelial cells (Fig. 4a, b), some intermingled with nests of cells having a prom- inent vacuolization and eccentrically placed nuclei conferring a signet ring cell appearance. The nuclei were otherwise uniform and round to oval, with no pleomorphism nor significant mitotic activity. In addition, there were scant islands of adipose and hematopoietic tissues resembling mature bone marrow (Fig. 2), with megakaryocytes, erythroid, myeloid, and lymphoid cells, with no precursor myeloblasts. The third component, accounting for 40% of the whole lesion, was composed by hyperplastic adrenocortical tissue lacking evident fibrous capsule (Fig. 2). By immunohistochemistry, a peripheral neural sheet derivation was confirmed for the first lesion, being melan-A and steroido- genic factor 1 negative (Fig. 3c) and S100 protein positive only (Fig. 3d). Conversely, the microcystic and tubular structures cov- ered by flattened cells displayed evidence of mesothelial differ- entiation, with a strong positivity for cytokeratin AE1/AE3, calretinin, and WT1 (Fig. 4c), in the absence of adrenocortical (melan-A, steroidogenic factor 1) and endothelial marker expres- sion (CD31, CD34, ERG) (Fig. 4d). Therefore, the morpholog- ical and immunophenotypical features of these lesions led to a diagnosis of a combined ganglioneuroma and adenomatoid tu- mor with foci of myelolipoma in an adrenal gland with nodular cortical hyperplasia.
☒ Eleonora Duregon eleonora.duregon@unito.it
1 Department of Oncology, University of Turin at San Luigi Hospital, Regione Gonzole 10, 10043 Orbassano, Torino, Italy
2 Department of Pathology, Martini Hospital, Turin, Italy
Comment
To the best of our knowledge, both adenomatoid tumors and ganglioneuromas have been reported in association either with
myelolipoma [1, 2] or adrenocortical adenoma [3, 4] or nod- ular cortical hyperplasia [5], but a quadruple combination of ganglioneuroma, adenomatoid tumor, myelolipoma, and nod- ular hyperplasia in a single tumor of the adrenal gland has not been described in the literature, so far. The uniqueness of this case is emphasized by the fact that at least two of the tumor components (adenomatoid tumor and myelolipoma) arise from tissues that are presumably foreign to those of the adre- nal gland. Adenomatoid tumors are benign neoplasms with mesothelial differentiation, which are usually found in the genital tract of both males (epididymis, testicular tunica, and spermatic cord) and females (uterus, fallopian tubes, and more rarely, ovary) [6]. As the coelomic epithelium gives rise to both mesothelial lining and adrenal cortex, it can be easily
understood why adrenal glands may host mesothelial- derived neoplasms such as adenomatoid tumors, generally thought to derive from mesothelial inclusions. In addition, the close embryologic relationship between adrenal gland and the mullerian tract can explain both heterotopic adrenal cortical tissue in the peri-ovarian region and adenomatoid tu- mor in the adrenal gland [7]. Among various hypotheses un- derlying the development of myelolipoma (bone marrow embo- lization, embryonic primitive mesenchymal cells, dysregulation of hematopoietic cell apoptosis), the most consistent is the dif- ferentiation of undifferentiated mesenchymal cells to myeloid and lipoid tissues activated by systemic stress from chronic ill- ness, necrotic tissue or high-energy trauma [8]. Similarly, to adenomatoid tumors, the presence of hematopoietic tissue in
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the adrenal gland can be explained embryonically because the adrenal cortex and bone marrow originate from the same mes- enchymal tissues [9]. This theory is supported by animal studies where myelolipomatous changes were seen after injecting ne- crotic tissues in rats [10]. However, the relationship and patho- genetic links between the medulla and cortex and their tumors, and therefore whether both components grow independently or in an interrelated manner remains unresolved. The imaging char- acteristics of both adrenal ganglioneuroma and adenomatoid tumor are quite variable being some very similar to other adrenal tumors such as adrenocortical carcinoma and pheochromocyto- ma [11]. Therefore, a definitive diagnosis can be obtained after
surgery, only. In our case, the ganglioneuroma was a discrete tumor, while the adenomatoid tumor was intermingled with hy- perplastic adrenocortical cells growing in a nodular fashion. Among the lesions encountered in this exceptional case, the most challenging for the pathologist is the adenomatoid tumor, as its lymphangiomatous and microcystic-cavernous growth patterns could be interpreted as a vascular neoplasm, particularly a lymphangioma [12]. However, the positivity for epithelial and mesothelial markers and the absence of vascular and lymphatic markers generally easily address to the correct differential diag- nosis. In addition, the complex tubules with adenoid appearance and those with a packed-solid growth with vacuolated cells may
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simulate metastatic adenocarcinoma or signet ring cell carcino- ma, but the lack of pleomorphism, mitotic figures, necrosis, and cellular atypia rules out the suspicion of malignancy [13]. Since seminomas are not very rarely combined with teratomas [14], and this patient had a recent history of testicular surgery, it had also to be excluded the event that the adrenal tumor was a metastasis from an unrecognized teratomatous component of the testis mass. After being entirely embedded, the testicular tumor was a classic seminoma, without any necrotic or hemor- rhagic areas, cystic changes or any non-seminomatous compo- nents, such as yolk sac tumor, choriocarcinoma, embryonal car- cinoma, and teratoma. The immunohistochemical stainings were consistent with the morphological features, being tumor cells positive for OCT3/4, c-Kit, placental alkaline phosphatase and weakly positive for cytokeratin AE1/AE3, while negative for alpha-fetoprotein, epithelial membrane antigen, CD30, in- hibin, and calretinin.
In conclusion, we reported an exceptionally rare benign adrenal lesion made of four components of different embryo- logical derivation, which expands the potential repertoire of combined tumors in the adrenal gland.
Compliance with Ethical Standards
Source of Support This study was supported by a grant from AIRC, Milan, (no. IG/14820/2013 to MP).
Conflict of Interests The authors declare that they have no conflict of interests.
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