BMC Research Notes
CASE REPORT
Giant nonfunctioning adrenocortical carcinoma: a case report and review of the literature
Ahmad Almarzouq1, Sami Asfar2, Sundus Hussain3, Adel Al-Hunayan4 and Saad Aldousari4*
Abstract
Background: Adrenocortical carcinoma is a rare and aggressive malignancy. Patients usually present early with manifestation of abnormal hormone secretion. However, adrenocortical carcinoma can also be nonfunctioning, and such patients present late with a mass effect or distant metastases.
Case presentation: We herein report a case of a 30-year-old Sri-Lankan woman who presented with a 3-month history of left flank pain associated with nausea, vomiting, and weight loss. Imaging revealed a large left upper quadrant mass with a 1.8-cm left lung nodule. The differential diagnoses included a left adrenal mass, left upper pole renal mass, and retroperitoneal sarcoma. A functional adrenal work-up revealed no abnormal findings. Surgical excision of the mass was uneventful with no postoperative complications. Pathological analysis revealed a nonfunctioning adrenocortical carcinoma measuring 16 x 14 x 10 cm. To our knowledge, a mass of this size is among the largest nonfunctioning adrenocortical carcinomas reported in the published literature. The investigations and approach to treatment were consistent with those in the published literature.
Conclusion: Large nonfunctioning adrenocortical carcinomas pose a diagnostic and therapeutic challenge, and most are diagnosed at a late stage. Appropriate imaging and functional work-up of the mass are vital before treatment. Surgical excision is safe, even for large adrenocortical carcinomas; excision in patients with advanced disease has been shown to have the best outcomes.
Keywords: Adrenocortical carcinoma, Adrenocortical mass, Giant, Nonfunctioning
Background
Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with an estimated annual incidence of one to two cases per million inhabitants in the United States [1,2]. The age distribution is bimodal, with peaks occur- ring at 5 to 20 and 40 to 50 years of age [1-3]. A slight female predominance has been shown [1].
Adrenal masses can be broadly divided into hyper- functioning (hormone-secreting) and nonfunctioning (non- hormone-secreting). Functioning ACC presents earlier with hormonal manifestations such as virilization, feminization, or Cushing’s syndrome. However, nonfunctioning tumors pose a diagnostic challenge because they are diagnosed inci- dentally due to a mass effect or metastatic disease. More- over, successful radical management is seldom achievable because most diagnoses are made when the tumor has
either invaded local structures or metastasized, explaining the poor prognosis associated with these masses [2,3].
Even after a grossly complete resection, most patients develop early tumor recurrence or distant metastasis [2]. This is presumed to be due to occult micrometastases that were not detected at the time of diagnosis [4,5]. The 5-year overall survival rate ranges from 16% to 44% [6]. However, a more recent case series suggested an improved 5-year overall survival rate reaching 60%; in this study, 34% of the enrolled patients had metastatic disease at diagnosis [6]. Early-stage disease in the absence of lymph node and distant metastases and an age of <40 years have been shown to be positive prognostic factors [7,8]. Add- itionally, negative resection margins have been shown to improve survival independent of other factors [9].
The most frequent metastatic sites are the lung, lymph nodes, liver, bone, and inferior vena cava at 71%, 68%, 42%, 26%, and 20%, respectively [10]. We herein present a case of a giant nonfunctioning ACC with local tumor effects.
* Correspondence: saad.aldousari@gmail.com
4Urology Unit, Department of Surgery, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait
Full list of author information is available at the end of the article
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Case presentation
A 30-year-old Sri-Lankan woman presented with left flank pain. The pain was intermittent, sharp, and of moderate se- verity and radiated to the groin. The patient reported no history of lower urinary tract symptoms or gross hematuria. The pain was associated with weight loss of 8 kg over a period of 3 months. Her medical and surgical history was not significant, and the patient was not on any regular medications.
The patient was afebrile on presentation with no micro- scopic hematuria. On physical examination, the abdomen was soft with minimal tenderness over the left flank, and a palpable left upper quadrant mass was present. The rest of the clinical examination revealed normal findings.
A computed tomography (CT) scan showed a large left upper quadrant mass measuring 17 x 13 × 12 cm in its greatest dimension. The mass crossed the midline and compressed the stomach, spleen, pancreas, and small
bowel (Figures 1 and 2). The origin of the mass was un- clear, and the differential diagnoses included a left adrenal mass, left upper pole renal mass, and retroperitoneal sar- coma. A functional adrenal work-up was performed ac- cording to the Canadian Urological Association guidelines and included measurement of serum aldosterone, potas- sium, renin, and adrenocorticotrophic hormone levels; a dexamethasone suppression test; and measurement of 24- hour urinary metanephrine levels. All results were within the reference ranges.
The metastatic work-up included CT scans of the head and chest and a bone scan. The head CT scan revealed normal findings. The chest CT scan showed a 1.8-cm nod- ule in the medial left lower lobe, close to the posterior mediastinum, as well as two subcentimetric nodules in the left lung. Neither the bone scan nor magnetic resonance imaging (MRI) showed evidence of bone metastasis. A de- cision was made to proceed with en bloc excision of the
NOT FOR MEDICAL USAGE
Figure 1 A coronal section of the abdomen and pelvis illustrating the size of the mass. The mass is shown compressing and displacing the adjacent structures and occupying the whole left upper quadrant.
NOT FOR MEDICAL USAGE
Figure 2 A cross section of the abdomen showing the large mass crossing the midline.
mass. Cardiothoracic surgeons were consulted regarding the suspicious lung nodules, and they planned to biopsy the lung lesion after excision of the primary tumor.
Operative findings
A Chevron incision was made, and a Gomez poly tract retractor (Pilling®) was used to ensure adequate expos- ure. The mass was exposed after medial reflection of the descending colon and was found to be displacing the stomach, pancreas, and spleen, but it had a grossly nega- tive margin with no evidence of adjacent organ invasion. The mass was covering the left renal hilum and was densely adhered to the aorta. After adequate exposure of the left kidney, the mass was noted to be densely ad- hered to the upper pole with no surgically defined plane. It seemed to be arising from the upper pole of the left kidney. In the presence of a vascular surgeon, the mass was dissected and the left renal hilum was carefully iso- lated. We decided intraoperatively to proceed with left radical nephrectomy. This decision was made to avoid positive surgical margins if partial nephrectomy was per- formed given the wide base of tumor adherence to the kidney. Upon vascular control of the left renal artery and vein, the mass significantly shrunk in size and be- came less congested. It was then easily dissected off the aorta. No enlarged lymph nodes were identified. After ensuring adequate hemostasis, Surgicel® Fibrillar™ was applied, and an intra-abdominal drain was inserted.
The postoperative recovery was uneventful. The drain was removed on postoperative day 2, and the patient was discharged on postoperative day 6. She was followed up 4 weeks postoperatively with no complications. After returning to her home country, her local cardiothoracic surgeon obtained biopsy specimens from the lung nod- ules; these were found to be benign granulomas. How- ever, contrast-enhanced CT of the chest, abdomen, and pelvis performed 3 months postoperatively showed new liver metastasis.
Histological findings
Histological examination showed a 1.63-kg en bloc left rad- ical nephrectomy specimen that measured 20.0- x 16.5- x 11.0-cm (Figure 3a and b). Opening of the specimen re- vealed a huge mass arising from the left adrenal gland measuring 16 x 14 x 10 cm. The tumor was tan-yellow and well demarcated, and it showed a clear line of cleavage from the left kidney. Histological examination of the tumor showed overt features of malignancy including a high nu- clear grade, high mitotic activity (>10/50 high-power fields), and foci of diffuse growth admixed with single infiltrating cells. Venous and capsular invasion was also present. Im- munohistochemistry revealed positive staining of tumor cells for synaptophysin and inhibin, supporting a diagnosis of ACC (Figure 4a-c). The margins were uninvolved by the tumor. In accordance with the 2010 Tumor Nodes Metas- tasis staging system, the tumor stage was pT3NxMx.
a
b
13-6971
Figure 3 Illustrates the extracted mass which includes the kidney and the adrenal gland. a) Gross appearance of the specimen showing a well-encapsulated mass with a distinct plane separating it from the kidney. b) En bloc specimen including the left kidney.
Conclusions
Approximately 60% of patients with ACC present with symptoms and signs of hormonal secretion. This was not a feature in the present case. Hormone secretion is not a
discriminating feature between benign and malignant adre- nocortical masses. The silent clinical nature of nonfunc- tioning ACC results in poorer outcomes. Hence, the majority of patients with nonfunctioning ACC present with
a
b
C
Figure 4 Illustrates the histopathological and immuno-cytochemistry stained slides as described in a, b and c. a) Hematoxylin and eosin stain of the adrenal gland. Right: Tumor. Left: Residual rim of normal adrenal gland (10x). b) Immunohistochemical stain: inhibin (10x). c) Immunohistochemical stain: vimentin (10x).
locally advanced and/or metastatic disease. The work-up for adrenal masses must include determination of whether the mass is functioning or nonfunctioning and whether it
is benign or malignant. Hormonal evaluation helps define the functional status of the tumor and can also help define its origin. Radiographic studies in the form of CT or MRI
can help define the size of the mass and rule out metasta- ses. Emerging evidence suggests that fluorodeoxyglucose- fused positron emission tomography with CT (FDG-PET/ CT) is superior to CT alone [11]. However, FDG-PET/CT is still considered a complimentary study and is not recom- mended for ACC work-up [11].
With the presence of a questionable metastatic pul- monary nodule and large tumor of >4 cm, the clinical suspicion of malignancy was high in this case and fa- vored radical adrenalectomy [12-14]. To the best of our knowledge, a mass of this size is among the largest non- functioning ACCs reported in the literature [15,16].
Despite the poor prognosis in this patient group, chemotherapy has a limited role in the treatment of ACC, and surgical resection has been shown to have the best outcomes [7,8]. However, recent studies have shown a role for adjuvant chemotherapy in prolonging recurrence-free and overall survival [5,8,9]. There is no established dur- ation of adjuvant chemotherapy. High-risk patients are currently being treated for 5 years with mitotane. In pa- tients with proven lung metastasis, the published evidence suggests that en bloc excision of involved organs and pul- monary metastasectomy could improve overall survival [5,8]. Postoperative surveillance for recurrence should be performed every 3 months for the first 2 years and then every 6 months for 5 years. Contrast-enhanced CT scans of the chest, abdomen, and pelvis are the standard of care for follow-up; however, FDG-PET/CT scans are used in some specialized centers and are still under investigation [11]. We have herein illustrated the successful and safe surgical resection of a large ACC with no postoperative complications. We will provide an update on the condi- tion and survival of the patient when available.
Consent
Written informed consent was obtained from the patient for publication of this Case Report and any accompany- ing images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Abbreviations
ACC: Adrenocortical carcinoma; CT: Computed tomography; MRI: Magnetic resonance imaging; FDG: Fluorodeoxyglucose; PET: Positron emission tomography.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
AAM: Designed the study and was involved in data acquisition, analysis, and interpretation. Was involved in drafting and critical revision of the manuscript and final approval of the version to be published. Is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. SA: Made substantial contributions to the study conception and design and to the data analysis and interpretation. Was involved in drafting and critical revision of the manuscript and final approval of the version to be published. Agrees to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work
are appropriately investigated and resolved. SH: Made substantial contributions to data analysis and interpretation. Was involved in critical revision of the manuscript and final approval of the version to be published. Agrees to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. AAH: Made substantial contributions to the study conception and design and data analysis and interpretation. Was involved in critical revision of the manuscript and final approval of the version to be published. Agrees to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. SAD: Was involved in the study design and data acquisition, analysis, and interpretation. Was involved in drafting and critical revision of the manuscript as well as final approval of the version to be published. Is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Author details
1Urology Unit, Department of Surgery, Mubarak Alkabeer Hospital, Kuwait City, Kuwait. 2Department of Surgery, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait. 3Department of Pathology, Mubarak Alkabeer Hospital, Kuwait City, Kuwait. 4Urology Unit, Department of Surgery, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait.
Received: 6 May 2014 Accepted: 18 October 2014 Published: 31 October 2014
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Almarzouq et al. BMC Research Notes 2014, 7:769 http://www.biomedcentral.com/1756-0500/7/769
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doi:10.1186/1756-0500-7-769 Cite this article as: Almarzouq et al .: Giant nonfunctioning adrenocortical carcinoma: a case report and review of the literature. BMC Research Notes 2014 7:769.
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