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Adrenocortical Carcinoma Arising in an Adrenal Rest: a Case Report and Review of the Literature
Kristine M. Cornejo 1,2,3 . Henrietta A. Afari4 . Peter M. Sadow 1,2
C Springer Science+Business Media New York 2017
Abstract Carcinomas arising from embryonic adrenal rests are rare with only a handful of reported cases. We report a case of an adrenocortical carcinoma arising from an adrenal rest located between the bladder and prostate in a 51 year-old man. The patient presented following a year of rectal pain and constipation. Computed tomography (CT) scan revealed a 9 cm pelvic mass that appeared to arise from the soft tissue between the bladder and prostate, with displacement of the organs and narrowing of the rectal lumen, suspected to be a sarcoma. The surgically resected specimen showed a well- circumscribed, partially encapsulated tumor measuring 10.0 cm in greatest dimension. Both adrenal glands were iden- tified intraoperatively. Grossly, the lesion was heterogeneous tan-brown to yellow, hemorrhagic and necrotic. Histology re- vealed sheets and nests of high-grade pleomorphic tumor cells with abundant clear to vacuolated cytoplasm with areas of necrosis, a high mitotic index (>10 mitoses/10 HPF) and foci suspicious for lymphovascular invasion. Adjacent adrenal cortical-type tissue was identified. Immunohistochemical stains revealed the tumor cells were weakly and focally posi- tive for MiTF, Melan-A, inhibin and synaptophysin, and neg- ative for CKAE1/AE3, HMB-45, calretinin, EMA, SMA, chromogranin, PAX8, MDM2 and CDK4. Based upon the
☒ Kristine M. Cornejo Kristine.Cornejo@umassmemorial.org
1 James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, MA, USA
2 Department of Pathology, Harvard Medical School, Boston, MA, USA
3 Department of Pathology, UMass Memorial Healthcare, One Innovation Drive, Biotech 3, Worcester, MA 01605, USA
4 Harvard Medical School, Boston, MA, USA
morphologic and immunohistochemical profile, this was di- agnosed as an adrenocortical carcinoma, arising in an adrenal rest. To our knowledge, no such tumor has been previously described in this location.
Keywords Adrenal rest · Adrenocortical carcinoma
Introduction
Morgagni in 1740 first described yellowish nodules resem- bling adrenal tissue adjacent to the gland [1-3]. Over a hun- dred years later in 1856, Piccolominus was the first to report accessory adrenal tissue [2, 4]. Adrenal rests, also known as ectopic or accessory adrenal tissue are fragments that break- off during embryological development. The adrenal cortex arises from the coelomic mesoderm of the urogenital ridge and the medulla arises from neural crest tissue which invagi- nates into the cortical tissue during embryology [3, 5, 6]. Depending upon when the break occurs, determines what type of tissue will remain, such that closer to the gland proper will result in cortex with or without medulla and more distant to the gland will result in cortex only [3, 7].
Adrenal rests can occur anywhere along the embryological path of migration usually related to gonadal descent, such as in the retroperitoneum, kidneys, broad ligament, ovaries, sper- matic cord, epididymis and testis. [2, 7] However, they have also been described elsewhere such as in intracranial and spi- nal locations and within the gastrointestinal system. [8-10] Adrenal rests are much more common in neonates and chil- dren (50%), and rarely persist into adulthood (1%) as func- tioning tissue or a neoplasm as it generally undergoes atrophy within a few years. [3, 6, 7, 11] However, it is exceptional for a malignancy to arise from an adrenal rest, with only a few cases reported. We present a case of an adrenocortical carcinoma
arising from an adrenal rest located between the prostate and bladder with a review of the English literature.
Case Report
A 51 year-old male with no significant medical history pre- sented with rectal pain and constipation for 12 months dura- tion. A computed tomography (CT) scan revealed a 9.0 cm pelvic mass that appeared to arise within the soft tissue be- tween the prostate and bladder, causing organ displacement and narrowing of the rectal lumen. Based upon the radiologic features, it was suspected to be a sarcoma. A resection of the neoplasm was performed requiring dissection off both the bladder and prostate with a partial colectomy, due to adher- ence to the rectosigmoid colon. Both of the adrenal glands were identified intraoperatively and were grossly unremarkable.
The specimen showed a well-circumscribed, partially encapsulated tumor measuring 10.0 cm in greatest
dimension. Grossly, the lesion was heterogeneous, tan- brown to yellow, hemorrhagic and necrotic. Histologic examination revealed sheets and nests of high-grade, pleomorphic cells with abundant eosinophilic to clear and vacuolated cytoplasm, with areas of necrosis and a high mitotic index (>10 mitoses/10 high-power field) (Fig. 1). Foci suspicious for lymphovascular invasion were also identified. Adjacent adrenal cortical-type tissue was also present, often in a lobular architecture. Immunohistochemical stains revealed the tumor cells were focally positive for MiTF, Melan-A, inhibin and synaptophysin. The tumor cells were negative for CKAE1/AE3, HMB-45, calretinin, EMA, SMA, chromogranin, PAX8, MDM2 and CDK4. Based upon the morphologic and immunohistochemical profile, this was diagnosed as an adrenocortical carcinoma (ACC), arising in an adrenal rest. The post-operative course was unremarkable, and he received adjuvant radiation and chemotherapy with mitotane. He had no evidence of disease at 9 months follow-up.
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| Case | Age (y) | Sex Location | Size (cm) | Wt. (gm) | Labs | Imaging | Initial Treatment | Follow-up | |
|---|---|---|---|---|---|---|---|---|---|
| Wallace et al. [9] | 23 | F Right liver | 18 | - | ¡Serum testosterone, 44-androstenedione, cortisol, prolactin. ¡ Urine 17-ketosteroid & 17-ketogenic steroids | Hepatomegaly with calcifications, irregular defects in right liver, both adrenal glands identified | - | DOD at 7 d post-admission due to large PE | |
| Goren et al. [11] | 50 | F | Hilum of left kidney | 8 | 150 | WNL | Echogenic mass in medial lower half ofkidney, displacing pelvicalcyeal system | Radical Nephrectomy | NED at 12 m |
| Yokoyama et al. [12] | 34 | F Retroperitoneum | 6.5 | 71 | Serum and urine WNL for adrenal function. | Retroperitoneal mass between right kidney and IVC. | Resection | NED at 120 m | |
| Akishima-Fukasawa et al. [13] | 31 | F Retroperitoneum below left kidney, extending to aortic bifurcation (fused with aorta, IVC, jejunum, pancreatic tail, bilateral ureters,) | 25 | - | ¡Serum cortisol & DHEA, JACTH | Large retroperitoneal mass along the abdominal aorta, both adrenal glands identified. | CT x 1 m | Multiple mets including supraclavicular LN, left adrenal gland, liver, lung, bilateral ovaries, BM, pericardium, pleura & peritoneum, DOD at 16 m | |
| Rodriguez et al. [14] | 0.4 | F Spinal cord at T10-L2 | 6 | - | No clinical evidence of endocrine dysfunction | Heterogeneously enhancing mass at T10-L2, both adrenal glands identified | Laminectomy with gross total resection | LR at 6 m s/p second gross total resection, undergoing CT (cisplatin, doxorubicin, etoposide, mitotane) 5 m post-op | |
| Engel et al. [15] | 3.4 | M Left testis | 9 | 1 Urine 17-ketosteroid & 17-hydroxycorticosteroid | (Both adrenal glands identified intraoperatively) | Resection | Developed signs of adrenocortical insufficiency at 12 h post-op, LR at 4 months s/p RT, obvious mets at 9 months involving abdomen below kidney, lymph nodes s/p RT, pulmonary mets at 12 m & DOD at 13 m due to a CVA with severe HTN and coma of sudden onset | ||
| Morimoto et al. [16] | 57 | M Left scrotum | 5 | 50 | ABNL glucose tolerance test, îurine 17-ketosteroid & 17-hydroxycorticosteroid | Tumorous density medial to left kidney (7 x 6 cm), left scrotal mass, bilateral lung densities, both adrenal glands identified | Laparotomy with removal of multiple masses medial to left kidney on renal vein and along abdominal aorta | DOD at 6 d post-op with tumor identified in the scrotum with mets involving the lung & retroperitoneum (identified at laparotomy) | |
| Contreras et al. [17] | 21 | F Right liver | 12 | 450 | 1Serum cortisol, 17ß-estradiol, 17-OH-progesterone, progesterone, testosterone, DHEASO4, turine 17-ketosteroids, estrone-3 «-glucuronide | Right liver mass, adrenal glands identified | Ketoconazole x 42 d followed by laparotomy | NED at 9 wks post-op | |
| Case | Age (y) | Sex Location | Size (cm) | Wt. (gm) | Labs | Imaging | Initial Treatment | Follow-up |
|---|---|---|---|---|---|---|---|---|
| Ney et al. [18] | 59 | M Retroperitoneum 8 cm above right kidney at level of L1 | 7.5 | 98 | ¡ Serum cortisol, hyperglycemia, furinary steroids | (Prior laparotomy removed atrophic adrenal glands) | Laparotomy | - |
| Raith and Karl [19] | 26 | F Cranial of left adrenal gland | 15 | - | 1 Urine 17-ketosteroids, HCG (confirmed pregnancy) | Tumor in upper pole of left kidney, left adrenal gland identified | Resection followed by irradiation with cobalt | NED at 15 m |
| Bani-Hani [20] | 52 | M Left retroperitoneum | 19 | 1950 | Adrenal function WNL | Retroperitoneal mass lying between spleen, stomach, tail of pancreas, splenic flexure & left kidney & adrenal gland | Resection | NED at 25 m |
| Jain et al. [22] | 65 | M Left testis | 8.5 | - | ¡ Serum cortisol, JACTH, hypokalemia, hypernatremia, hyperglycemia, turine free cortisol level | Left testicular mass, right testicular mass (3.1 x 2.3× 1 cm), mediastinal, supraclavicular & retroperitoneal LAD, retroperitoneal mass, both adrenal glands identified | Radical orchiectomy | Mitotane started 3 m post-op, DOD 2 m after last discharge with episodes of delirium |
| Current case | 51 | M Pelvis | 10 | - | Adrenal function WNL | Pelvic mass arising within the soft tissue between the prostate and bladder, both adrenal glands identified | Resection followed by mitotane & RT | NED at 9 m |
ABNL, abnormal; BM, bone marrow; cm, centimeters; CT, chemotherapy; CVA, cerebrovascular accident; d, days; DOD, died of disease; F, female; gm, grams; hrs, hours; HTN, hypertension; LAD, lymphadenopathy; LN, lymph nodes; LR, local recurrence; m, months; M, male; mets, metastasis; NED, no evidence of disease; PE, pulmonary embolism; post-op, post-operatively; RT, radiotherapy; s/p, status post; WNL, within normal limits; wks, weeks; y, years
Discussion
Tumors arising from adrenal rests are uncommon and most are functional, resulting in an endocrinopathy, and are often diag- nosed pre-operatively [11]. Infrequently are they non-func- tional, usually discovered incidentally or at time of autopsy [11]. Malignancies arising from adrenal rests are extremely rare with only a handful of cases reported and their clinico- pathologic features are summarized in Table 1 [9, 11-21]. Malignant tumors arising from adrenal rests have been de- scribed in 13 patients, including our current case at a mean age of 36.4 years (0.4-65 years) with an equal female to male ratio (7:6). The tumors were located in the retroperitoneum (n=5), testis/scrotum (n=3), liver (n=2), kidney (n=1), spinal cord (n=1) and pelvis (n=1). Eight (62%) tumors were func- tioning, with patients most commonly presenting with Cushing’s syndrome.
Histologically, the differential diagnosis of ACC is broad and includes metastatic renal cell carcinoma (RCC), hepatoid variant of yolk sac tumor (YST), melanoma, malignant leydig cell tumor and liposarcoma [20]. Rarely, extra-adrenal neo- plasms such as hepatic and Leydig cell tumors have been reported to produce ectopic cortisol, adrenocorticotropic (ACTH) and cortisol-releasing factor (CRF) [9, 22]. The pat- tern of immunohistochemical findings such as positive inhib- in, Melan-A, MiTF and synaptophysin markers, suggest an adrenal cortex origin of the tumor cells and are expressed in ACC and help to exclude other malignancies in the differential diagnosis [20, 22].
Based upon our review of the literature, 11 of 13 cases (85%) underwent surgical resection with one case treated with chemotherapy alone (8%) and 5 (38%) cases treated with ad- juvant chemotherapy and/or radiotherapy. Surgical resection is the mainstay of treatment with potential for cure in ACC [20, 23]. The 5 and 10-year survival in patients who underwent resection for ACC was 26-38% and 7%, respec- tively [23-25]. The patients with early mortality, were found to have higher rates of cortisol-secreting tumors, positive re- section margins and higher stage with nodal or synchronous distant metastasis [23-25]. The importance of surgery was further confirmed by long-term survival attained with repeat resection of local or distant tumor recurrence [23].
In our review, 6 (50%) patients were diagnosed with tumor recurrence and/or metastases, of which 5 died of disease at a mean of 6.3 months (6 days-16 months) [9, 13-16, 22]. Five patients were without evidence of disease at a mean follow-up period of 26.4 months (2.25-120 months). All 5 patients underwent surgical resection for a primary tumor without ev- idence of nodal or distant metastasis, of which 2 were treated with adjuvant chemotherapy and/or radiotherapy [11, 12, 17, 19, 20].
The role of adjuvant chemotherapy and radiation is limited and unclear. Mitotane is the most common chemotherapeutic
agent used to treat ACC with limited response [20, 26]. Tumors which do show response may obtain prolonged sur- vival, with significant benefit found in patients not cured sur- gically or with an increased risk of recurrence [20, 25, 26]. Moreover, additional studies have found a significantly longer recurrence-free survival in patients treated with adjuvant mitotane therapy after radical surgery [26].
Adjuvant radiotherapy remains controversial with studies showing conflicting results, some revealing an advantage with significant reduction of local recurrence, while others showing no added benefit [27-29]. Functioning carcinomas with pro- duction of steroids may also benefit from treatment with agents such as ketoconazole by blocking adrenal steroid syn- thesis, such as the case reported by Contreras and colleagues [17].
The prognosis of patients with ACC is poor, with recur- rence and metastasis being common [20, 26]. The manage- ment of patient’s with more advanced disease in which surgi- cal resection is not optional or curative may benefit from a combination of loco-regional resection, chemoembolization, radiofrequency (RFA) and/or systemic chemotherapy [26]. The combination of cytotoxic chemotherapy plus mitotane may also be beneficial in a subset of patients with advanced or metastatic disease with reduced progression-free survival [26].
Conclusion
In summary, we report the unique occurrence of an adreno- cortical carcinoma arising from an adrenal rest within the pel- vis, located between the prostate and bladder. Frank features of histologic malignancy were present. Although the occur- rence of malignancies arising from adrenal rests is rare, pa- thologists should be aware that they can occur, particularly within any location along the path of embryologic migration of the genitourinary tract.
Compliance with Ethical Standards
Conflict of Interest None.
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