American Journal of
Case Reports
| Received: | 2018.03.28 |
| Accepted: | 2018.06.30 |
| Published: | 2018.09.15 |
Laparoscopic Trans-Abdominal Right Adrenalectomy for a Large Primitive Adrenal Oncocytic Carcinoma: A Case Report and Review of Literature
ABCD 1 Valerio Panizzo
BC 2 Barbara Rubino
ABCDEF 3 Guglielmo Niccolò Piozzi
ABCD 4 Paolo Ubiali
ABCDEF 5 Anna Morandi BCDF 6 Marco Nencioni
ABCDEF 1,7 Giancarlo Micheletto
1 Department of General Surgery, Istituto Clinico Sant’Ambrogio, Milan, Italy
2 Department of Pathology and Cytodiagnostic, IRCCS Policlinico San Donato, Milan, Italy
3 General Surgery Residency Program, University of Milan, Milan, Italy
4 Department of General Surgery, Santa Maria degli Angeli Hospital, Pordenone, Italy
5 Department of Pediatric Surgery, Fondazione IRCCS Ca’ Granda - Maggiore Policlinico Hospital, Milan, Italy
6 Department of General Surgery, San Raffaele Hospital, Milan, Italy
7 Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Corresponding Author: Conflict of interest: None declared
Guglielmo Niccolò Piozzi; e-mail: guglielmopiozzi@gmail.com
Patient: Male, 48
Final Diagnosis:
Adrenal oncocytic carcinoma
Symptoms: Asymptomatic
Medication:
—
Clinical Procedure:
Specialty:
Transabdominal laparoscopic right adrenalectomy Surgery
Rare disease
Objective: Background: Adrenocortical oncocytic neoplasms (AONs) are extremely rare tumors. AONs are classified as: oncocytoma (AO), oncocytic neoplasm of uncertain malignant potential (AONUMP), and oncocytic carcinoma (AOC). Among the 162 reported cases of AONs in the literature, 30 cases were classified as malignant. Adrenalectomy is the treatment of choice for AON.
Case Report:
We report the case of a 48-year-old man with a primitive 12-cm mass affecting the right adrenal gland, detect- ed by ultrasonography during follow-up for alcoholic liver cirrhosis. Computed tomography (CT) scan and mag- netic resonance imaging (MRI) showed a mass of the right adrenal gland compressing the inferior vena cava (IVC) and dislocating the right lobe of the liver, with no invasion of kidney, liver, or IVC. Preoperative blood tests showed mild transaminase increase. Laparoscopic right adrenalectomy with lateral transperitoneal approach was performed. The postoperative course was uneventful. The lesion was diagnosed as a primitive adrenal on- cocytic carcinoma (AOC). No recurrence was evidenced during 24-month follow-up.
Conclusions:
Although AONs are very rare, they must be considered in the differential diagnosis of adrenal masses due to their prognostic difference compared to non-oncocytic tumors. AOCs are a rare presentation of AONs. Only 30 cases are described in the literature. Laparotomic adrenalectomy is the treatment of choice for AOC. We report the first case of laparoscopic lateral trans-abdominal adrenalectomy for a voluminous AOC (120×95×110 mm) and we review the literature regarding AOCs. Laparoscopy in experienced hands is safe and effective for the treatment of AONs. Despite the rarity of AOC, a case series should be performed to confirm the results of our case report.
MeSH Keywords: Adrenal Gland Neoplasms . Adrenalectomy . Adrenocortical Carcinoma . Laparoscopy
Full-text PDF: https://www.amjcaserep.com/abstract/index/idArt/910259
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Authors’ Contribution:
Study Design A
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Statistical Analysis C Data Interpretation D Manuscript Preparation E Literature Search F Funds Collection G
Background
Oncocytic neoplasms (ONs), or oncocytomas, are tumors that are mainly composed of oncocytic cells. Oncocytic cells were described for the first time by Hamperl in 1931 as large, high- ly eosinophilic, granular cells with pyknotic nucleus, typically associated with a Hurtle cell tumor of the thyroid gland [1,2]. The cytoplasmic granularity is characterized by a striking ac- cumulation of mitochondria, as demonstrated through elec- tron microscopy in 1986, that can occupy up to 60% of the cy- toplasm volume [3,4]. ONs arise in various organs, including kidney, thyroid, pancreas, parathyroid, salivary, lacrimal, pitu- itary glands, paraganglia, respiratory tract, paranasal sinus- es, pleura, liver, pancreatobiliary system, stomach, colon, rec- tum, central nervous system, female and male genital tracts, skin, and soft tissues [5-21]. ONs arising from adrenal glands are extremely rare and were first described by Kakimoto et al. in 1986 [22]. Adrenocortical oncocytic neoplasms (AONs) are usually observed to be non-functional and mostly benign tu- mors. AONs are classified as: oncocytoma (AO), oncocytic neo- plasm of uncertain malignant potential (AONUMP), and onco- cytic carcinoma (AOC) [23]. Since the first description, a total of 162 cases of AONs have been reported, with 30 cases de- scribed as AOC [23,24]. Tumor size is considered to be a prac- tical sign to differentiate benign from malign disease in adre- nocortical carcinomas (diameter <4-5 cm suggests a benign mass). However, in case of AONs, the size of the mass and the imaging findings (through abdominal CT scan and MRI) are not pathognomonic or related to malignancy [24]. Because AONs are non-functional, differential diagnosis should be done with indeterminate adrenal tumors (incidentalomas). AONs are usu- ally detected as a large mass with an average diameter of 8 cm (range 2-20 cm) [25]. Adrenalectomy is the treatment of choice for AONs. Surgical approaches to adrenal gland include laparot- omy, combined thoraco-abdominal access, retroperitoneal pos- terior access, laparoscopy, and robotic surgery [27]. Since the first successfully laparoscopic adrenalectomy (LA) performed by Gagner in 1991 [28], the lateral trans-abdominal approach has become the most common therapeutic strategy for adrenal neoplasms [29-34]. To the best of our knowledge, this is the first case report of laparoscopic lateral trans-abdominal adre- nalectomy for a large AOC (12 cm) (Supplementary Video 1).
Case Report
A 48-year-old man was admitted to our Surgical Department for a primitive 12-cm mass affecting the right adrenal gland. The mass was detected by abdominal ultrasound during an- nual follow-up for liver cirrhosis (Child-Turcotte-Pugh score A). The patient was submitted to contrast-enhanced abdominal CT scan in our hospital (Figure 1) and contrast-enhanced abdomi- nal MRI in another institute with evidence of a capsulated solid
adrenal mass (diameters: 120×95×110 mm) with an irregular vascularization pattern, compressing the inferior vena cava, and dislocating the right lobe of the liver. A cleavage plane be- tween the liver and the right kidney was evident with no lym- phonodal or any other intra-abdominal neoplastic involvement. Preoperative laboratory tests (including cortisol, 17-ketoste- roids, and 17-hydrocorticosteroids serum levels), dexametha- sone test, complete blood count test results, and renal function were all normal, while liver enzyme levels were mildly elevat- ed. The patient was a non-smoker, chronic alcohol abuser (1-2 bottles of wine per day). No endocrinopathy sign or symptoms were identified. Therefore, a non-functional adrenal mass was diagnosed, but no preoperative US- or CT-guided fine-needle aspiration cytology was performed because of the wide size of the mass, which made surgery mandatory. Considering the presence of a clear cleavage plane between the adrenal lesion and the liver, the kidney, and the surrounding vascular struc- tures, and the absence of evident lymphonodal or other vis- ceral involvement, a laparoscopic approach was attempted. In fact, despite the size of the lesion, no signs of malignancy or infiltration were found preoperatively, thus making the lap- aroscopic approach laborious but feasible and oncologically radical in skilled hands. The patient underwent lateral trans- abdominal laparoscopic right adrenalectomy with a standard 4-trocars technique in left lateral decubitus position. During the operation, the IVC was easily dissociated from the lesion, and en-bloc right adrenalectomy was completed with no cap- sule rupture. Extraction was performed in toto. No major bleed- ing and no major intraoperative complications were encoun- tered. The patient remained hemodynamically stable during the procedure. The postoperative course was uneventful and the patient was discharged on the 5th postoperative day in good condition. Macroscopic examination of the specimen revealed
a solid mass, measuring 123×98×113 mm, weighting 300 g, with several necrotic areas. Microscopic examination report- ed a primitive oncocytic adrenal carcinoma (Figure 2). Several atypical mitotic figures and high mitotic index (10/50 HPFs) were observed, together with diffuse pattern of growth and venous invasion. The patient’s Weiss score was 5 and, accord- ing to modified Weiss score, the patient had an AOC. The tu- mor cells were immunopositive for vimentin and presented typical oncocytic architecture. KI-67 and MIB1 rate was 20%. The patient was not eligible for therapy with mitotane (RS)-1- chloro-2-[2,2-dichloro-1-(4-chlorophenyl)-ethyl]-benzene due to the chronic liver disease. He was submitted to follow-up with an abdominal CT scan performed every 6 months for the first year and once during the second year. No recurrence was evidenced during 24-month follow-up.
Discussion
Adrenocortical carcinoma (AC) is a rare and aggressive tumor of the adrenal cortex that accounts for 0.2% of all malignancies (prevalence 1-2 cases per million) [35]. AONs are an extreme- ly rare subtype of AC, with 162 cases reported in the literature since the first description in 1986 [18]. AONs are usually inci- dental [36-41] with only 17% cases described as functional [42]. AONs do not have a precise peak incidence, with a mean age at diagnose of 47 years (range 27-72 years) [25]. AONs occurs more frequently in females (F/M: 2.5/1) and on the left side (L/R: 3.5/1) [25]. AONs are located in the adrenal cortex, with only 1 case reported within the adrenal medulla and 1 with- in heterotopic adrenal tissue [43,44]. To date, no specific risk factors have been identified and the pathogenesis of oncocy- tosis is still unclear. Krech et al. [45] demonstrated the role of N-nitrosomorpholine, an airborne contaminant, as a chemical inducer of oncocytosis in renal tissue of Sprague-Dawley rats, managing to generate an in vivo model resembling human on- cocytoma. However, no further experimental studies have been reported using this rat model. Oncocytes have characteristic
| Weiss criteria | Score |
|---|---|
| High nuclear grade (III-IV) | 1 |
| Atypical mitotic figures | 1 |
| Mitotic rate >5/50 HPF | 1 |
| Eosinophilic tumor cell cytoplasm (>75% of tumor cells) | 1 |
| Diffuse architecture (>33% of tumor) | 1 |
| Necrosis | 1 |
| Venous invasion | 1 |
| Sinusoidal invasion (no smooth muscle in wall) | 1 |
| Capsular invasion | 1 |
severe mitochondrial anomalies: mitochondria are numerous with an excess of cristae mitochondriales. The shape varies from round and oval to extremely elongated, slender, or cup- shaped, often piled up to form complex bodies; mitochondria can rarely form large ramifying organelles [45]. Some authors reported a role of mitochondrial genome mutation in oncocy- tosis pathogenesis [46,47]. Duregon et al. analyzed the pres- ence of the mtDNA 4977 bp “common deletion”, present in 50% of AOCs, as a potential pathogenetic interest, but to date, it has no practical diagnostic value [47]. Macroscopically, AOCs are large, rounded, encapsulated, brown-yellow, and well-cir- cumscribed masses with an average diameter of 8 cm (range 2-20 cm) and a thin rim of normal adrenal gland. The mean AOCs weight is 281 g (range 8-865 g) [48]. Microscopically, AOCs can appear with solid, trabecular, tubular, or papillary patterns. AOCs are characterized by: diffuse proliferation of polygonal cells with abundant granular and eosinophilic cyto- plasm, large nuclei and prominent nucleoli, occasional mono- nuclear and binucleated giant cells, extracapsular extension with blood vessel invasion and necrosis, and variable atyp- ia and mitotic figures [49]. The immunophenotypic profile of AONs is diffuse positivity for vimentin, melan-A, synaptophy- sin, and alpha-inhibin [50-52]. AONs are classified as oncocy- toma (AO), oncocytic neoplasm of uncertain malignant poten- tial (AONUMP) [48], and oncocytic carcinoma (AOC) [19,53-56]. The Weiss Criteria are considered the standard tool for diagno- sis of AC [57]. This system considers 9 criteria (nuclear grade III-IV; mitotic rate >5/50 HPFs; atypical mitotic figures; eosin- ophilic tumor cell cytoplasm (>75% of tumor cells); diffuse ar- chitecture (>33% of tumor); necrosis; venous invasion, sinu- soidal and capsular invasion) (Table 1). A 1-point score is given to each parameter. Malignancy can be suspected when 4 or more of the 9 criteria are met. However, care should be tak- en in applying these criteria during pathological evaluation of
| AON subtypes | Criteria |
|---|---|
| AOC | One of the following 3 (major criteria) |
| Mitotic rate >5/50 HPF | |
| Atypical mitotic figures | |
| Venous Invasion | |
| AONUMP | At least one of the following 4 (minor criteria) |
| Size >10 cm and/or weight >200 g | |
| Necrosis | |
| Capsular invasion | |
| Sinusoidal invasion | |
| AO | Lack of major and minor criteria |
the rare and peculiar AOC. Bisceglia et al. proposed a review of the Weiss Criteria, proposing major and minor criteria for AOC diagnosis (Table 2) [58]. AOC is characterized by the presence of 1 of the following 3 (major criteria): mitotic rate >5/50 HPF, atypical mitotic figures, and/or venous invasion. AONUMP is characterized by at least 1 of the following 4 (minor criteria): size >10 cm and/or weight >200 mg, necrosis, capsular inva- sion, and/or sinusoidal invasion. AO is characterized by the ab- sence of both major and minor criteria. Several molecular and biological studies have been performed on AC to characterize the malignancy and establish new ocnological parameters [59- 64]. However, no established premalignant condition has been documented in the human adrenal cortex and no adrenocorti- cal adenoma to AC transition has been described. Furthermore, there are very few cases of AOC described in the literature, with few molecular studies. In addition, ACs are markedly het- erogeneous morphologically and functionally, even within the same tumor [65]. Among several molecular and/or cytological markers that may contribute to the differential diagnosis of adrenocortical carcinoma, the cell proliferation markers, such as Ki-67 and topoisomerase, and oncoprotein p53, can be of most value [59-64,66-69]. Unfortunately, the role of either Ki- 67 or p53 as biomarkers remains uncertain due to the avail- ability of so few of these tumors [70,71]. However, according to Mearini et al., MIB1 and Ki- 67 are of practical value in or- der to achieve a differential diagnosis between benign mass and adenocarcinoma [25].
The size and the function of the lesion are considered the most important factors in the diagnosis of an adrenal mass. In a report on 887 patients who had adrenal incidentalomas, a diameter greater than 4 cm was shown to have a 90% sen- sitivity for the detection of AC, but a low specificity (only 24%
of the lesions were malignant) [72]. Increase in size over time is another indication for surgery. Generally, resection is rec- ommended for adrenal masses > 6 cm. Biochemical analyses should be undertaken to rule out the presence of a primary functioning mass, which requires resection despite the size.
Imaging has a major role during differential diagnosis between AC, included AONs, from adrenal adenomas. Fat concentration may be used as a tool to differentiate between benign and ma- lignant adrenal lesions: with the first being lipid-rich. The CT criteria for the diagnosis of adrenal adenoma are unenhanced attenuation of 10 or fewer HUs [73] and absence of necrotic or cystic areas, which can be seen in some malignant lesions and adrenal cysts [74]. However, it has not been demonstrat- ed to be a characteristic imaging for AON; therefore, CT imag- ing findings are generally nonspecific [75-77]. MRI with chem- ical shift subtraction [78] provides a high confidence level in distinguishing adrenal adenomas from other disease [79,80]. However, MRI is considered not specific for AON detection [81].
Although the use of contrast-enhanced ultrasound has shown an excellent sensitivity and specificity in the differential diag- nosis between benign and malignant adrenal mass, no typi- cal pattern has been described for AONs [82].
Fine-needle aspiration cytology and open biopsy are help- ful during perioperative diagnosis of AC; however, they are not able to specifically characterize and define AONs [83,84].
Adrenalectomy is the treatment of choice for AON. Different surgical approaches are available to treat adrenal masses. The surgical approach choice depends on several parameters: tu- mor size, malignancy, patient condition, and surgical experi- ence [85]. The surgical approach to adrenal gland includes lap- arotomy, combined thoraco-abdominal access, retroperitoneal posterior access, laparoscopy, and robotic surgery [86]. Since the first successfully laparoscopic adrenalectomy (LA) per- formed by Gagner in 1991 [28], the lateral trans-abdominal approach has become the most common therapeutic strate- gy for adrenal neoplasm [28-34]. LA is associated with low- er postoperative pain, reduced ileus, shorter hospitalization, earlier return to work, and a better cosmetic result, guaran- tying a lower morbidity (5-20%) and mortality rate (below 0.5%) compared to open adrenalectomy [25,31,34]. In con- trast, open adrenalectomy is associated with higher mortality (2-4%) and morbidity rates (bleeding, pulmonary and cardiac complications, pulmonary thromboembolism, and wound in- fections) and is reserved worldwide only for large tumors (di- ameter >6 cm) and primary malignancies, based on the rad- icality of resection, minor tumor local recurrence, and major survival [27,87,88]. The mainstay of the surgical procedure is to perform a complete resection of the adrenal gland without disruption of the adrenal capsule. Therefore, the presence of
capsular or vascular invasion, infiltration of surrounding tis- sues, and lymphonodal involvement represent the major con- traindications to LA. Several different laparoscopic techniques have been proposed and are currently used for the resection of adrenal tumors [27]. Each technique has its own advantag- es and disadvantages. Lateral trans-abdominal adrenalecto- my (LTA) is the most common adrenalectomy technique used by general surgeons. Compared with the retroperitoneal ap- proach, LTA provides more working space, which can be ben- eficial for large tumors and morbidly obese patients. In addi- tion, the lateral decubitus position used during this approach enables excellent exposure of the adrenal gland because of the effect of gravity on the abdominal organs. Posterior ret- roperitoneoscopic adrenalectomy (PRA) [27] is characterized by enhanced visualization following the use of higher insuf- flation pressures in the retroperitoneal cavity, as well as di- rect access to the adrenal gland (avoiding the intra-abdominal cavity), making it attractive in case of prior abdominal surgery. Additionally, the prone position facilitates equal access to the right and left sides, allowing bilateral procedures without the need for patient intra-operative repositioning. The disadvan- tages include lack of access to the intra-abdominal cavity for evaluation, difficult removal of large tumors, and increased dif- ficulty with increasing body mass index (BMI). Anterior trans- abdominal adrenalectomy [27] is a sub-mesocolic approach and is the least common technique used for adrenalectomy; its main appeal is the conventional abdominal laparoscopic view, familiar to all general surgeons. However, the operating times are generally longer, and more ports are needed for a successful operation. Lateral retroperitoneoscopic adrenalec- tomy (LPA) [27] is the most common technique used by uro- logic surgeons for adrenalectomy, likely due to their familiarity with the anatomy of laparoscopic nephrectomy. Similar to PRA, LPA is advocated for patients with prior abdominal surgery.
AONs are very rare lesions, with 162 reported cases in the lit- erature and only 30 cases reported as AOCs. To the best of our knowledge, this is the first reported case of laparoscop- ic adrenalectomy for a voluminous AOC (120×95×110 mm). Following CT and MRI imaging, a well-encapsulated tumor, with no evidence of invasion of the surrounding tissues and no regional adenopathy, was detected. In our case, laparo- scopic approach with 4-trocar placement was chosen. The pa- tient was positioned in left lateral decubitus position at a 60° angle. The table was flexed for space widening between the 12th rib and the iliac crest. Four ports were used. The proce- dural steps included: mobilization of the right triangular liga- ment of the liver, incision between the retroperitoneal attach- ments of the right hepatic lobe and the lateral border of the
inferior vena cava (IVC), dissection of the lateral edge of the IVC, and taking of the right adrenal vein at the takeoff from the IVC. Mobilization of the gland was performed with an in- ferior-to-superior and medial-to-lateral approach. The surgi- cal procedure was safe and effective and the postoperative period was uneventful. The 24-month follow up was nega- tive for disease recurrence. Macroscopic examination of the specimen revealed a solid mass weighting 300 g, with several necrotic areas. Microscopic examination showed a primitive oncocytic adrenal carcinoma. Several atypical mitotic figures and high mitotic index (10/50 HPFs) were observed, togeth- er with diffuse pattern of growth and venous invasion. The specimen was evaluated with a final Weiss score of 5 (necro- sis, high mitotic rate >5/50 HPF, atypical mitotic figures, dif- fuse architecture, and venous invasion). According to modi- fied Weiss score, an AOC was diagnosed (mitotic rate >5/50 HPF, atypical mitotic figures, and venous invasion). The tumor cells were immunopositive for vimentin and presented typical oncocytic architecture. In our case, the neoplastic cells had a KI-67 and MIB1 rate of 20%.
In 2013, the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) presented guidelines for mini- mally invasive treatment of adrenal pathology [27]. However, these guidelines are limited to a retrospective analysis of pub- lished case series, with no specificity for AONs. In our case, we performed an effective laparoscopic approach to a volumi- nous AOC, with 24-month follow-up negative for recurrence. In light of our result, a prospective multicentric observational study should be performed to better define the aims and lim- its of minimally invasive surgery for AON. Due to the scarci- ty of cases, it is difficult to establish precise guidelines on the management of adrenal oncocytic neoplasms. Our case report is fully compliant with SCARE criteria [89].
Conclusions
Adrenocortical oncocytic tumors must be taken into ac- count in the differential diagnosis of adrenal masses due to their different prognosis compared to non-oncocytic tu- mors. Adrenocortical oncocytic carcinoma are a rare presen- tation of AONs. Only 30 cases are described in the literature. Laparotomic adrenalectomy is the treatment of choice for AOC. We report the first case of laparoscopic lateral trans-ab- dominal adrenalectomy for AOC, despite the large size of the mass (120×95×110 mm). Laparoscopy performed by an expe- rienced surgeon is safe and effective for AOC. Despite the rar- ity of AOC, a case series should be performed to confirm the results of our case report.
Supplementary Video
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