TJ
Tumori Journal
Xanthogranulomatous adrenalitis masquerading as a functioning adrenocortical malignancy: a case report
Tumori Journal 1-5 @ Fondazione IRCCS Istituto Nazionale dei Tumori 2020 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/0300891620949656 journals.sagepub.com/home/tmj OSAGE
Kalkunte Sriram Jayanth’ (D, S. Balamurugan’, Sathasivam Sureshkumar’ (D, Amaranathan Anandhi’, J. Sree Rekha2, K.M. Abdulbasith1, B.S. Rajesh1 and Muhamed Tajudeen’
Abstract
Introduction: Xanthogranulomatous adrenalitis (XA) is a rare chronic inflammatory disease of the adrenal glands and resembles adrenal neoplasm in clinical and radiologic characteristics. There is no report on XA presenting as a functioning adrenal mass in the literature. We present a case of XA mimicking a functioning adrenocortical carcinoma. Case report: A 52-year-old man presented with right flank pain, fever, vomiting, and loss of appetite for 2 weeks. He had signs of dehydration and elevated blood glucose level. Ultrasonography revealed a right adrenal mass. Contrast-enhanced computed tomography showed lobulated and necrotic mass replacing the right suprarenal gland and encasing the right renal vein, adjacent inferior vena cava, psoas, and diaphragm. There was loss of fat planes with liver and upper pole of the right kidney. Biochemical evaluation indicated increased serum and urine cortisol levels. As a sequel to hypercortisolism- induced hyperglycemia, he developed spontaneous chest wall abscess and bilateral sudden vision loss due to vitreous hemorrhages. Pus and blood culture grew methicillin-sensitive Staphylococcus aureus. Adrenal suppressant ketoconazole was administered for better glycemic control. With a diagnosis of locally advanced adrenocortical malignancy, right radical adreno-nephrectomy was performed, and cut section revealed a pus collection of around 100 mL. Histopathology examination showed xanthogranulomatous inflammation involving adrenal gland, Gerota’s fascia, psoas, and lymph nodes. Postoperatively, the patient recovered satisfactorily with favorable glycemic control.
Conclusion: XA can mimic adrenal neoplasms both clinically and radiologically and is associated with staphylococcal infection. It warrants surgical excision and culture-based antibiotics and is mostly diagnosed on postoperative histopathology.
Keywords
Xanthogranuloma, adrenalitis, Staphylococcus aureus, adrenal malignancy, functioning adrenal tumor
Date received: 14 May 2020; revised: 10 June 2020; accepted: 10 July 2020
Introduction
Xanthogranulomatous inflammation refers to a rare chronic inflammatory process with common occurrence in retroperitoneal organs. It is postulated to occur in a back- ground of hemorrhage or staphylococcal infection leading to the formation of chronic suppurated necrotic mass.1 Although it is frequently reported to occur in renal paren- chyma that may closely mimic renal cell carcinoma, the involvement of adrenals is extremely uncommon. Primary adrenocortical neoplasms are very rare, characterised by intense local aggressiveness coupled with an inherent
resistance to chemotherapy and radiation. Considering the risk of tumor seeding and tumor spillage and also the risk
‘Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
2Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
Corresponding author:
Dr. Sathasivam Sureshkumar, Additional Professor, Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Dhanvantri Nagar, Puducherry, 605006, India. Email: drsureshkumar08@gmail.com
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involved in the release of life-threatening catecholamines in case of pheochromocytoma, biopsy in adrenocortical mass is contraindicated except in carefully selected cases. The retroperitoneal location and risk of significant hemor- rhage from hypervascular tumors also makes biopsy tech- nically difficult. Therefore radical surgery is the only potential therapeutic modality for pathologic confirmation as well as a cure.
Xanthogranulomatous adrenalitis (XA) poses a diag- nostic dilemma for treating surgeons as it can closely mimic an adrenocortical tumor in clinical, radiologic, and functional aspects. To our knowledge, there are no afore- mentioned reports of hormone-secreting adrenal masses due to XA. We report a case of a functioning right adrenal mass diagnosed as XA on postoperative histopathology.
Case report
A 52-year-old man presented with abdominal pain for 2 weeks’ duration predominantly in right hypochondriac and lumbar regions. There was associated high-grade continu- ous fever for 5 days and bouts of nonbilious vomiting. The patient also complained of decreased urine output for a day with no alteration in bowel habits. He had diabetes diag- nosed 2 years previously and was on medication with poor drug compliance. At the time of admission, his blood glu- cose profile was slightly elevated with no evidence of urine ketosis. On examination, the patient was febrile and tachycardie with high blood pressure recordings of 160/90 mm Hg. He had pallor and signs of dehydration, with no findings suggestive of generalized lymphadenopathy. On examination of cardiovascular and respiratory systems, no abnormalities could be detected. Abdominal examination revealed localized tenderness over the right lumbar region with no evident mass. He also had a concomitant reducible type of right inguinoscrotal hernia. On preliminary inves- tigations, hematologic parameters pointed towards anemia
(6.7 mg/dL) and leukocytosis (18,000/mm3). Biochemical investigations showed derangements in renal function tests, while liver function tests and lipid profile was normal.
Ultrasonography of abdomen revealed a large hypo- echoic mass in the right suprarenal region with no internal moving echoes or calcifications. Right kidney exhibited mild altered echoes with preserved dimensions. Contrast- enhanced computed tomography (CECT) (Figure 1) was done with adrenal protocol, which further delineated a het- erogeneously enhancing ill-defined mass of dimensions 9×8×12 cm. The mass was predominantly in the retro- renal region infiltrating Gerota’s fascia with indistinct fat planes to the right kidney. It was also encasing the right renal vein, with infiltration into inferior vena cava (IVC), under surface of the right lobe of liver and right psoas mus- cle. The mass was largely necrotic with a solid enhancing component in the periphery. A strip of adrenal tissue was present in the periphery of the tumor. A provisional diag- nosis of adrenocortical tumor with hemorrhagic and necrotic component was made.
The patient had sudden onset of bilateral vision loss on the second day of presentation. Direct ophthalmos- copy revealed bilateral vitreous hemorrhages with pre- retinal membranes, which was attributed to highly fluctuant blood glucose levels. The patient also devel- oped right upper limb weakness, which was evaluated with magnetic resonance imaging of cervical spine. This was found to be due to acute cord edema and radiculopa- thy, which was also a probable sequel of poor glycaemic control. His blood glucose was highly fluctuant for a period of 2 weeks, even with periodic monitoring and dosage titration.
The patient had development of spontaneous abscess in the right sternoclavicular region, which was managed by incision and drainage. Pus culture showed positive growth suggestive of methicillin-sensitive Staphylococcus aureus
(MSSA). His blood culture also indicated MSSA, follow- ing which he was initiated on intravenous antibiotics based on sensitivity, which induced defervescence.
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The patient’s basal serum cortisol was raised and 24-hour urinary cortisol was significantly elevated. The hypercortisolism was found to be nonresponsive to dexa- methasone suppression. Other assays, which included serum adrenocorticotrophic hormone (ACTH), 17-hydroxy progesterone, dehydroepiandrosterone sulphate (DHEAS), plasma metanephrine, and urinary vanillylmandelic acid (VMA), were found to be within normal limits.
Following the hormonal workup and CECT, an endo- crinologist was consulted and a diagnosis of cortisol- secreting adrenocortical malignancy was made. Ketoconazole and steroid suppression therapy was initi- ated, following which gradual glycemic control was achieved as a result of normalized cortisol levels. After optimization, the patient underwent surgery under general anesthesia with curative intent. Intraoperatively (Figures 2 and 3), a large necrotic tumor was found posterosuperior to the right kidney extensively infiltrating the Gerota’s fascia. It had posterior infiltration to the right psoas and hemidia- phragm and superior infiltration to the undersurface of the liver. The tumor was completely encasing the right renal vein and adherent to the right border of IVC. The mass was completely excised with contiguous part of the liver, right psoas, diaphragm, and a cuff of IVC, along with right nephrectomy. The diaphragm was sutured and IVC rent was primarily repaired. Inter-aortocaval lymphadenec- tomy was also performed. Postoperatively, the patient was given a stress dose of steroids, which was gradually tapered
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and stopped. His cortisol levels came within normal limits without the need for steroid suppressant and his blood glu- cose was well controlled. The patient recovered well with- out any major postoperative complications.
On pathologic examination of the specimen (Figure 4), grossly it was an unencapsulated, ill-defined, gray-white mass of dimensions 10.5×6.5×5.5 cm. It had interspersed yellow areas as well as focal areas of cystic degeneration and necrosis. On cut section, a cavity was noted, filled with 100 mL of pus, which was sent for culture and later turned out positive for MSSA. Microscopic examination revealed dense inflammatory aggregation of periodic acid- Schiff (PAS) positive foamy histiocytes and plasma cells, and was negative for acid-fast bacilli. The field showed lymphocytes and polymorphs along with both foreign body and touton giant cells. Final histopathologic exami- nation confirmed the xanthogranulomatous inflammation, with no focus of neoplasia.
Discussion
Xanthogranulomatous process (XP) is a rare clinicopatho- logic entity characterized by chronic inflammation. It is often incited by triggering factors like hemorrhage, necro- sis, or a severe infection. It has been well documented to involve retroperitoneal organs, most notably the kidneys.1,2 It may also involve the gallbladder and bones, or even more rarely bronchi, parts of the gut, and very rarely the pancreas or lymph nodes.1
First described in the early 19th century by Oberling3 as retroperitoneal xanthogranuloma, XP is an entity that closely mimics malignancy, making its preoperative diag- nosis rarely possible.1,3 Classically it is characterized by the presence of PAS-positive foamy macrophages in a
background of plasma cells, lymphocytes, and poly- morphs. All the cellular components mentioned conglom- erate to suppurated foci with areas of hemorrhage. Immunohistochemistry often exhibits positivity to a-1 antitrypsin, a-1 antichymotrypsin, and lysozyme.1
XA is rarely described in medical literature, and the first documentation of xanthogranulomatous inflammation of adrenals was by Grimi et al in 1987.4 Later, Atiemo et al.5 reported a case of contralateral XA in a patient with a history of radical nephrectomy for renal cell carcinoma. He opined that XA in that patient was probably a conse- quence of postsurgical retroperitoneal inflammation. There has been mention of the association of diabetes and immu- nosuppression with XA in the literature.6 In another report by Trinavarat et al.,7 neonatal adrenalitis due to XP was speculated to be triggered by adrenal hemorrhage follow- ing birth asphyxia and neonatal sepsis. Although it is believed that XP follows a benign course, there can be sig- nificant local infiltration into adjacent organs, which makes it indistinguishable from adrenal neoplasms in most scenarios.
Sepsis is generally believed to be the inciting event for the process, and in our case systemic staphylococcal sep- ticemia was present, similar to previous reports.6 However, in contrast to previous studies, the present case had isola- tion of MSSA strains, instead of methicillin-resistant infection. The clinical features described are usually non- specific with a palpable mass and dull aching flank pain. Unexplained fever and weight loss are also commonly seen.
The radiologic findings can mimic a possible list of dif- ferentials including myelolipoma, adrenocortical tumor, and either functioning or nonsecretory tuberculous adrenalitis. In our patient, provisional diagnosis of
adrenocortical malignancy was made based on the CT findings of large mass replacing the right adrenal with encasement of renal vein and surrounding infiltrations coupled with biochemical and clinical evidence suggesting hypercortisolism. Preoperatively or intraoperatively, the diagnosis of XA was not considered. The tumor was removed with the psoas muscle, with nonanatomical resec- tion of liver and a cuff of diaphragm along with lymph nodal sampling. As it was found to be completely encasing the renal vein and adjacent IVC, nephrectomy was also carried out.
The current patient presented with poorly controlled diabetes for 2 years. Considering the association of diabe- tes with XA, it could be possible that in the present case, xanthogranulomatous inflammation was aggravated by poor glycemic control. The possibility of Cushing syn- drome was considered at presentation. However, it was excluded as the hypercortisolism was found to be nonre- sponsive to dexamethasone suppression, and serum ACTH and DHEAS were within normal limits. Glycemic control was achieved and there was normalization of cortisol lev- els after the complete resection of tumor, indicating a cor- tisol secreting adrenal mass due to XA.
Conclusion
XA is a difficult preoperative diagnosis to make. In most cases, adrenalectomy is the employed modality of treat- ment along with perioperative parenteral antibiotics for achieving defervescence and avoiding recurrence. Some authors argue for adjuvant chemoradiotherapy in case of large tumor size. However, standard recommendations for treatment are unlikely to emerge considering the rarity of the disease process. Therefore, individual case-based deci- sion-making is recommended after multidisciplinary
discussions. XA as a rare clinicohistopathologic entity will continue to remain an enigma for adrenal surgeons.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
ORCID iDs
Kalkunte Sriram Jayanth İD https://orcid.org/0000-0002-4186
-3545
Sathasivam Sureshkumar İD https://orcid.org/0000-0001-6435 -421X
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