Large Adrenal Lesion Series in a Tertiary Care Center in Northern India: Diagnostic and Operative Challenges

Abstract

Large adrenal tumors pose varied challenges to surgeons in terms of diagnosis, planning surgical approach, and also intra-operative difficulties in resection. The aim of this study is to discuss challenges in the management of large and difficult adrenal lesions. A retrospective analysis was done on data of all patients with large adrenal lesions/paragangliomas managed from 1 June 2016 to 30 August 2018. Forty-eight patients with adrenal lesions underwent treatment in 2 years duration. Pain in the abdomen was the most common presentation. Mean age was 34.4 years (range 2–60), female to male (23:25) and right to left side to bilateral tumor 30:16:2. Thirty-one (64.6%) patients had large adrenal masses (size > 6 cm). Surgical approaches included open transperitoneal adrenalectomy (n = 20) and laparoscopic transperitoneal (n = 9 and 2 others had conversion to open procedure). Challenges faced are described in the table below:

Tumor	Difficulties handled
Teratoma	Large calcified and retrocaval cystic areas difficult to resect, extensive liver mobilization.
Myelolipoma with bleeding	All adjacent planes destroyed by contained hematoma. Decision to embolize and then operate or directly operate was difficult.
Large right ACC with renal involvement	Kidney pushed up and out.
Large left ACC	Splenomegaly hampered dissection.
Neuroblastoma	Large tumor mass indenting and displacing IVC, infiltrating liver and kidney. It was downstaged by chemotherapy and then resected.
Malignant left pheochromocytoma	Large extensively infiltrated left adrenal mass led to difficult dissection in posterior and medial planes close to great vessels.
ACC with Cushing’s	Immunocompromised state, poor lung capacity.
ACC	For IVC + right atrium thrombus with distant metastases given EDP-M regimen, disease stable for 3 months, then progressed.
Ganglioneuroma	Para-spinal thoracic mass, on CECT? abdominal mass
Right side adrenal lesions	Hepatomegaly hampering planes of dissection in laparoscopic surgery

There were no major peri-operative morbidities, but two patients died in perioperative period. Large adrenal tumors pose a challenge in surgical planning, approach, and resection and need careful planning and multidisciplinary team approach to have the best outcomes.

Introduction

Large adrenal lesions (LALs) are defined based on size > 6 cm. LALs pose challenges in diagnosis, surgical planning, and treatment. Best patient outcome depends on multidisciplinary approach. The large-sized lesions distort the anatomy and surrounding planes. Triple-phase contrast-enhanced CT scan images sometimes fail to provide all the minute details about the local invasion/infiltration of the adrenal mass. Hence, we need to co-relate all the clinical, radiological, biochemical, and pathological findings to have proper pre-operative planning. Apart from surgical expertise, we need a competent endocrinologist, pathologist, radiologist, and nuclear medicine physician for having a multi-disciplinary approach to management. We also need a dedicated anesthesiologist to take care of all intra-operative hemodynamic instabilities and manage them timely and appropriately. Patient presentation is varied and mostly lesions are detected on incidental imaging done for some sort of vague abdominal symptomatology. Our center is based in North India, a Government University where treatment is subsidized and patients come from economically compromised population mostly. We will be discussing challenges we faced in managing such difficult lesions to have a better understanding and to improve precision in their treatment planning and disease outcome.

Aim

The aim of this study is to discuss challenges in the management of large and difficult adrenal lesions.

Method

Retrospective analysis was done by collecting and analyzing data of all patients admitted with large adrenal lesions from 1 June 2016 to 30 August 2018. We will discuss different pathological variants (adrenal teratoma, myelolipoma with bleed, pheochromocytoma, neuroblastoma, adrenocortical carcinoma, ganglioneuroma) of large adrenal tumors and also discuss the difficulties we faced and managed. Data regarding demography, clinical presentation, disease duration, workup, surgery, and follow-up were all recorded.

Results

Total of forty-eight patients with adrenal lesions underwent treatment in 2 years duration. Abdominal pain was the most common presentation. Mean age was 34.4 years (range 2–60), female to male (23:25) and right side to left side to bilateral tumor 30:16:2. Thirty-one (64.6%) patients had large adrenal masses (size > 6 cm) with mean adrenal tumor size being 12.21 cm (range 6–28 cm). Seven patients had pre-operative core tissue biopsy (done CT guided). Reasons for doing guided biopsy were to plan medical management in adrenal granulomatous disease (n = 1), chemotherapy in inoperable large adrenocortical carcinoma (n = 5), to downstage disease in large inoperable neuroblastoma (n = 1). Surgical approaches included open transperitoneal adrenalectomy (n = 20) and laparoscopic transperitoneal (n = 9 and 2 others had conversion to open procedure).

Table 1 shows the pathological variants of adrenal lesions, surgery done, and peri-operative complications.

Table 1.

Pathological variants of adrenal lesions, surgery done, and peri-operative complications

Diagnosis	Patient Number (n = 48)	Number of patients with large adrenal lesions	Surgery done	Peri-operative complications
ACC	9	8	7/9 patients underwent surgical excision 2 had palliative chemotherapy only	Minor wound dehiscence in 2 patients, infection in 1, hematoma in 1. All managed conservatively
Pheochromocytoma	23	9	23 patients had adrenalectomy	2 patients had laparoscopic consversions to open surgery due to bleed and adhesions. 1 peri-operative mortality in malignant pheochromocytoma
Myelolipoma	7	7	5/7 operated	1 wound infection managed conservatively
Neuroblastoma	1	1	Excision	–
Ganglioneuroma	3	3	All had excision	–
Paraganglioma	4	3	All had excision	–
Adrenal TB	1	0	Managed medically	–

Few Interesting Cases with Learning Points

Case 1: A 27-year-old lady presented with complaints of abdominal pain for 1-month duration and on evaluation was found to have large 18 × 16 cm right adrenal mass which was non-functional biochemically. CT scan showed large heterogeneous right adrenal mass with calcifications (Fig. 1). We did open transperitoneal right adrenalectomy after adequate liver mobilization to get better exposure. We found difficulties in resection over the hard calcified mass in subhepatic area and cystic areas where the tumor was going retrocaval. Histopathology was reported as an adrenal teratoma (Fig. 1). She is doing well in the last 2 years of follow-up.

Fig. 1.

CT scan showed large heterogeneous right adrenal mass with calculations

Lessons learned were to have proper adequate liver mobilization which may be learnt technically as this helps to lift the whole of liver medially and upwards to have better exposure and make dissection easier. Retrocaval area is a critical area where hepatic veins and IVC injuries may happen, most local recurrences post adrenalectomy happen in this area as some adrenal tissue may be left behind if not properly dissected and hence need careful dissection.

Case 2: A 30-year-old man presented with sudden severe right-sided upper abdominal pain for 15 days duration. He was normotensive and no significant family history pertaining to endocrine syndromes. CT scan of the abdomen showed 28 × 25 cm large right adrenal myelolipoma with hemorrhage confined to retroperitoneum (Fig. 2). Biochemical workup was normal. He was always hemodynamically stable by his clinical parameters. We had a dilemma regarding first to embolize the tumor or directly go ahead with surgery. He was stable clinically and no derangement in his vitals so we planned to embolize but due to financial constraints, he refused the procedure and opted for surgical exploration. He underwent interval surgery after 4 weeks in form of open trans-peritoneal right adrenalectomy.

Fig. 2.

CT scan abdomen showed 25 × 22 cm large right adrenal myelolipoma with hemorrhage confined to retroperitoneum and intra-op specimen showing areas of fat and myeloid components. Histology showing myelo = hemtopoietic element (Erythroid, myeloid, and megakaryocytes) and lioma = adipocytic component (fat)

We found difficulties in dissecting the planes which were disrupted by the contained hematoma and blood confined to retroperitoneum. However, by careful dissection, we could save the kidney and other adjacent structures. Post-operative period was uneventful. Histopathology was adrenal myelolipoma with rupture of the capsule leading to bleeding (Fig. 2). He is doing well in the last 2 years of follow-up.

Lesson learned was that in cases of adrenal hemorrhage, it is better to do open surgery instead of laparoscopic approach as the planes will be disrupted and surgery should be anticipated to be difficult. We need to have a mental image of the tumor as an operating surgeon as the tumor will be surrounded by all hematoma and we may not see the capsule of the tumor mass due to all disrupted planes.

Case 3: A 13-year-old adolescent boy presented with complaints of abdominal pain and fullness for 2 months duration. He was normotensive and no significant family history pertaining to endocrine syndromes. On evaluation CT scan showed large 25 × 22 × 20 cm right adrenal mass abutting the liver, IVC, and kidney with few areas with loss of fat planes (Fig. 3). Biochemical workup showed elevated 24 h urinary nor-metanephrine levels. MIBG scan was positive.

Fig. 3.

Pre-NACT. CT scan showed large 25 × 22 × 20 cm right adrenal mass abutting liver, IVC, kidney with few areas with loss of fat planes. Incisional biopsy: small round cell tumor with Homer-Wright pseudorosettes along with areas of necrosis. Differential diagnosis: (a) Neuroblastoma. (b) Neuroectodermal tumor (PNET). Consistent with neuroblastoma. Post NACT, CT scan shows tumor size reduction. Intra-opeerative specimen showing adrenal mass and omental nodules

As it was considered to be unresectable due to infiltration in the liver and indenting IVC and the kidney, we planned to do tissue biopsy to explore the role of systemic neo-adjuvant chemotherapy to downstage the disease. He was given alpha-blockers and then CT-guided core tissue biopsy was done from the mass which was reported as neuroblastoma. In view of the pathology and large unresectable adrenal mass, we discussed with a pediatric oncologist and then planned him for chemotherapy to downstage the disease to make it operable. He received cisplatin, etoposide, doxorubicin, and cyclophosphamide regimen and became symptomatically better. After completion of chemotherapy, CT scan showed almost 50% reduction in mass and curved IVC became straight (Fig. 3). He underwent surgery after finishing all cycles of chemotherapy. The whole of the omentum was adherent to the tumor mass, and there were two omental nodules of 2 × 2 cm size each which were excised (Fig. 3). Few lymph nodes peri-tumoral region were enlarged and were also excised. It was a large hard calcified tumor mass with difficult planes of dissection; however, the kidney could be identified and was saved. He had moderate BP fluctuations intra-operatively. Post-operative period was uneventful.

Histopathology was neuroblastoma with metastatic nodules and lymph nodal metastases (Fig. 3). He received adjuvant radiation therapy and then MIBG therapy. He is doing well in 1 year of follow-up.

Lesson learned: Neoadjuvant chemotherapy helps to downstage disease especially in locally advanced neuroblastomas and makes the tumor resectable. Multidisciplinary team meetings help to make optimum decision for the patient.

Case 4: A 63-year-old lady presented with abdominal pain and on evaluation CT scan showed large 25 cm by 23 cm by 22 cm right retroperitoneal mass which had displaced the right kidney up and also infiltrated it (Fig. 4). Her biochemical workup was normal. She underwent resection by open transperitoneal approach. Intra-operative the tumor was hard densely infiltrated the right kidney; hence, en bloc excision of mass with nephrectomy was done. Post-operative period was uneventful. Histopathology was adrenocortical carcinoma infiltrating the right kidney (Fig. 4). She received adjuvant therapy (RT and Mitotaine).

Fig. 4.

CT scan (large 25 cm by 23 cm by 22 cm right retroperitoneal mass displaced right kidney up and infiltrated). Histology: ACCs

Learning point: In large ACC, adjacent structures like the kidney may be displaced in abnormal anatomical locations and renal vasculature may also come on the way of resection and hence we need to interpret the findings on CT scan images carefully and plan surgical steps while resection.

Case 5: A 38-year-old lady presented with left side flank pain for 2 months duration. On evaluation, she had CECT scan of abdomen which showed 18 × 15 × 14 cm large left adrenal mass with multiple lymph nodes adjacent to the mass (Fig. 5). She was biochemically non-functional. She underwent open transperitoneal left adrenalectomy with splenectomy and lymph nodal dissection. Intra-operatively splenomegaly was hampering the dissection as the adrenal mass was hard and had difficult planes of dissection, however, free from kidney. Histopathology was adrenocortical carcinoma with metastatic lymph nodes (Fig. 5). She was planned for adjuvant therapy (RT and Mitotaine).

Fig. 5.

18 × 15 14 cm large left adrenal mass with splenomegaly and multiple lymph nodes adjacent to the mass

Learning point: Be cautious if splenomegaly is there along with ACC tumor mass which may be locally infiltrating. Splenectomy may be required for better exposure inspite of full splenic mobilization. On the left side, we dissect near renal hilum which makes it more prone for injury if not identified timely and anatomical knowledge and understanding should be adequate to avoid such injuries. Pancreatic tail is also in proximity and needs to be identified and spared.

Case 6: A 40-year-male patient presented with HTN and left adrenal large mass 20 × 15 × 12 cm, biochemically raised nor-metanephrine levels suggesting of Pheochromocytoma. In view of a large infiltrating adrenal mass, we suspected malignant pheochromocytoma and planned for open adrenalectomy after an adequate alpha blockade. Intra-operatively, the mass was densely infiltrating the adjacent structures and it was very difficult to dissect and create planes for dissection. He had BP fluctuations also intra-operatively. He had almost 1 l of blood loss which was replaced; however, he could not be extubated and was on inotropic supports in post-operative ICU and succumbed 6 h later.

Lesson learned was we must anticipate difficult dissection in patients with malignant pheochromocytoma and have a very competent team to manage all intra-operative events.

Case 7: A young lactating lady presented with Cushingnoid features and had large 16 × 12 cm right-sided adrenal mass. Open transperitoneal approach was planned. The tumor mass was very hard and infiltrating the adjacent structures. Her chest was also affected by the disease. She could not be extubated and was shifted in ICU and succumbed few hours later due to low blood pressures not responding to ionotropes and bad chest condition.

Lesson learned: Severe hypercortisolism manifests with chest infections, immune-compromised state and surgery involves high risk and decision regarding surgery must be taken after weighing all risks and benefits.

Case 8, 9: Two patients presented with large ACC with IVC and right atrium thrombus and lung metastases. The dilemma was in decision-making: surgery versus chemotherapy.

After multidisciplinary team meetings, we gave them EDP-M regimen, one patient improved for the next 3 months but then developed liver metastases and succumbed after few months and other patients had a fall and died due to fractured ribs and pneumothorax.

Lesson learned: ACC per se has dismal prognosis and those who present with major vein thrombosis with distant metastases have a worse outcome. Hence, palliative systemic therapy should be a valid option and role of heroic extensive surgery is limited.

Case 10: A 9-year-old male child presented with pain in upper abdomen and upper back region for 2 months duration. On evaluation, he was normo-tensive, no significant family history, non-functional biochemically, and CT scan showed large 15 × 12 cm paraspinal mass lesion on the right side (Fig. 6). MRI was done to look for any intra-spinal extension. Intra-operatively, the whole mass was intra-thoracic and was excised after opening the diaphragm. At few areas, it was densely adherent to adjacent vertebra; otherwise, the rest of the planes were free and resectable. Post-operative period was uneventful. Histology was ganglioneuroma.

Fig. 6.

Paraspinal mass lesion

Lesson learned: We need to read CT scan images very carefully as sometimes, it is difficult to clarify planes of the mass lesion from the diaphragm and mass can mimic to be intra-abdominal in adrenal region but in reality may be a large intra-thoracic mass which can be excised by thoracotomy approach. Surgical approach changes with location and size of the mass.

Discussion

The data is scarce when it comes to define the road-maps for management of large adrenal tumors and hence less is described about their surgical techniques and overall management. For surgeons, appropriate preoperative planning is a must for safe adrenal surgery. A close anatomical relationship with liver, hepatic veins, bowel, kidney and renal hilum, spleen, pancreatic tail, and inferior vena cava leads to the associated risk of injury to these structures. Tumor size, site, pathology, and surgical expertise are all factors which make surgical resection technically demanding.

Appropriate surgical approach for such large adrenal lesions is still debated and we need to tailor-made and select the appropriate option for each patient after proper planning. The various surgical approaches include open transperitoneal/ transthoracic/retroperitoneal, laparoscopic transperitoneal, retro-peritoneoscopic, and robotic adrenalectomy.

Since the first description of laparoscopic adrenalectomy (LA) by Michel Gagner in 1992, it has become the standard of care [1, 2]. Various studies have demonstrated reduced post-operative ileus and pain, minimal morbidity, and excellent cosmesis [1, 3, 4]. Parnaby et al. compared the outcomes of LA for patients with tumors ≥ 6 cm and < 6 cm and found no significant difference among the two groups in the absence of local invasion [5]. By our case series, we have realized that in presence of local invasion suspected on imaging, open approach is preferred as we need to mobilize the tumor and mobilize the liver extensively on the right side and spleen on the left side to have better exposure all around the tumor for dissection purpose.

Castillo et al. showed that LA in LALs (> 8 cm) is associated with prolonged operative time, increased blood loss, and longer hospitalization, without affecting perioperative morbidity [6]. The tumor dimension > 12 cm was considered a contraindication to laparoscopic adrenalectomy in striking contrast several recent studies have shown that LA might be performed safely even for masses up to 15 cm [1, 7–14]. Even for pheochromocytoma > 6 cm, LA has shown to be safe and effective although patients with such large tumors may have a higher conversion rate and more intraoperative hypertensive crises [15].

The concept of reteroperitoneoscopicadrenalectomy (PRA) was described first by Brunt in 1993 [16]. Walz improvised the technique and demonstrated its safety and enhanced visualization with the use of higher insufflation pressures in the retroperitoneal cavity [17]. PRA has advantages of direct access to the adrenal gland thus avoiding the intra-abdominal cavity, making it appropriate in the setting of prior abdominal surgery [18, 19]. Bilateral procedures performed by PRA facilitates equal access and do not require repositioning between sides [20, 21]. Main disadvantage is difficulty in removing large tumors due to small retroperitoneal space and increased difficulty with increasing BMI [17, 20]. In our series, we found that in morbidly obese patients (BMI > 35 kg/m²) and for large tumors (> 6 cm), the lateral transabdominal approach is preferred as it may increase the feasibility of resection.

The first robotic adrenalectomy (RA) was performed by Horgan et al. in 2001 [22]. Brunaud reported the largest series to-date of lateral transabdominal RA and showed that RA might be especially useful for patients with a high BMI (> 30–35 kg/m²) with large tumors [23, 24]. Similarly, Nordenstrom and colleagues reported similar advantages in obese patients and large tumors in their series [25]. Recently popularized single incision adrenalectomy offers no significant benefit in patient length of stay or morbidity and only a small benefit in cosmesis and post-operative pain but longer operative time [26–28].

Traditionally, in open surgery, right adrenalectomy is considered technically more demanding than its left-sided counterpart. This belief is supposed to be attributable mainly to anatomic characteristics of the adrenal—when enlarges usually become retrocaval in location with proximity to multiple hepatic veins and hence greater degree of liver retraction and mobilization is required on right side surgery.

Floppy large liver may create a problem in LA as we may find it difficult to retract large floppy liver and this may hamper in our dissection. We need to look for hepatomegaly in CT scan films before planning surgical approach for the patient with right sided lesions. The right adrenal vein is relatively short and drains directly into the vena cava inferior postero-laterally and may cause technical difficulties.

In context of laparoscopic adrenalectomy, such opinion may be debatable. Operating on the left side has its own difficulties like proximity to tail of the pancreas and splenic vasculature, mobilization of splenic flexure, and dissection close to renal hilum, and hence leading to more chances of hilar injury.

Kokorak et al. studied differences in laparoscopic left and right adrenalectomy from an anterior approach in 176 patients and found no significant difference in terms of operating time, occurrence of serious intraoperative complications, conversion rate, or post-operative outcome [29].

While comparing between different pathologies, there is much published literature of comparison of pheochromocytoma vs. other pathologies. Nowadays pheochromocytoma is conveniently operated through laparoscopic approach due to improvement in imaging methods, perioperative care, anesthesia, and pharmacological preparation [30]. It was reported that the operative time of LA for pheochromocytoma is more in comparison to other lesions. It is often due to gentle handling and meticulous dissection of the gland so as to avoid any chance of bleeding from the highly vascular tumor and higher pressure on the gland itself leads to more catecholamine release into the circulation thereby producing more hemodynamic alterations [30, 31].

Natkaniec et al. showed in their study that the histological type of tumor has no significant impact on the incidence of complications and conversions, and adrenalectomies performed for pheochromocytoma are equally safe [32]. Halil Bozkur et al. compared various intra-operative (operation time, blood loss, complications, conversion to open, the difference between left-/right-sided tumor) and post-operative parameters (hospital stay) for tumors > 8 cm vs < 8 cm and found no significant correlation between the evaluated parameters and size of the adrenal mass.

The risk of finding incidental adrenal cortical cancer was significantly increased for large masses [33]. Many authors reported successful management of large adrenal tumors laparoscopically, even above 10 cm [34–37]. Although the size of adrenal tumor is often correlated with the risk of malignancy, the small diameter does not guarantee the benign behavior, because as many as 13.5% of the resected adrenal cortical carcinomas are < 5 cm in diameter [38]. We prefer favoring open adrenalectomy in view of difficult dissection due to local invasion of the malignant adrenal mass, avoiding port site metastasis, intra op tumor spillage, and hence achieving more chances of complete resection.

Kebebew et al. evaluated the outcomes of 20 LA performed for suspected malignant adrenal tumors [39]. They reported 65% overall disease-free survival at mean follow-up of 3.3 years and 60% rate of loco-regional recurrence that was similar to the reported open adrenalectomy rates. Heniford et al. reported successful LA in 11 of 12 adrenal cortical cancers [40]. One patient switched to an open procedure due to local vascular tumor invasion. Halil Bozkurt et al. also found similar results in their series—seven adrenal cortical carcinomas were detected and five of them were 8 cm in diameter. Conversion to an open procedure was required in only one patient because of local invasion. On follow-up, intraperitoneal recurrence or trocar site seeding was not detected in any of the patients [33]. In our case series, we found local invasion as one the main factors favoring open surgical approach.

Myelolipomas have a risk of rupture and hemorrhage and the risk increases as the size of the lesion increases. Most bleeds are restricted in retroperitoneum area; however, occasionally, the bleed may spread in peritoneal cavity. In such patients, it is always better to go for open transperitoneal approach as the planes will be affected by the hematoma and we must anticipate a difficult dissection.

Conclusion

Adrenalectomy for large adrenal tumors pose a challenge in surgical planning, approach, and resection and need careful planning and multidisciplinary team approach to have the best outcome. Laparoscopic Adrenalectomy has been the standard of care and can safely be carried out for large tumors. However, we must not compromise on exposure and dissection and hence we must not hesitate to convert to open approach whenever it is needed and dissect the adrenal after adequate mobilization of adjacent structures.