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Year : 2020  |  Volume : 63  |  Issue : 2  |  Page : 335-337
Amyloidosis presenting as right adrenal mass—diagnosed on endoscopic ultrasound-guided fine needle aspiration

1 Department of Pathology, Medanta-The Medicity, Gurugram, Haryana, India
2 Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurugram, Haryana, India
3 Institute of Digestive and Hepatobiliary Sciences, Medanta-The Medicity, Gurugram, Haryana, India

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Date of Web Publication18-Apr-2020

How to cite this article:
Thakur A, Sarin H, Choudhary NS, Mohapatra I, Puri R, Soin A S. Amyloidosis presenting as right adrenal mass—diagnosed on endoscopic ultrasound-guided fine needle aspiration. Indian J Pathol Microbiol 2020;63:335-7

How to cite this URL:
Thakur A, Sarin H, Choudhary NS, Mohapatra I, Puri R, Soin A S. Amyloidosis presenting as right adrenal mass—diagnosed on endoscopic ultrasound-guided fine needle aspiration. Indian J Pathol Microbiol [serial online] 2020 [cited 2021 Nov 27];63:335-7. Available from: https://www.ijpmonline.org/text.asp?2020/63/2/335/282701

Dear Editor,

Amyloidosis can be a diagnostic challenge in cytology smears especially in the absence of clinical suspicion. Amyloid can be confused with other substances like mucus, alveolar proteinosis, colloid, necrosis, or chondroid depending on the organs involved.[1] Adrenal gland may be affected in systemic amyloidosis. However, to the best of our knowledge, adrenal mass presenting as the initial manifestation of amyloidosis has not been described before. We present an interesting and rare case of right adrenal amyloidosis diagnosed on Endoscopic ultrasound-guided Fine needle aspiration cytology (EUS-FNAC).

A 72-year-old male presented with complaints of right hypochondrial pain and loss of weight and appetite. His routine laboratory investigations revealed raised serum creatinine (2.6 mg/dl) and urine protein creatinine ratio (1.53). His liver function tests were within normal limits. Ultrasound (USG) abdomen revealed a large mass likely arising from right adrenal gland. Triphasic positron emission tomography-computed tomography (PET CT) showed large (15 × 15 × 15 cm) well-defined lobulated mass with mild fluorodeoxyglucose (FDG) avidity [standardized uptake value (SUV) max 4-4.3] in right adrenal gland. Left adrenal gland also showed a hypodense nodule measuring 16 × 13 mm with no significant FDG uptake. Spleen was mildly enlarged while liver was normal in size with no space occupying lesion. His serum tumor markers [carcinoembryonic antigen (CEA), alfa-fetoprotein (AFP), and carbohydrate antigen 19-9 (CA19-9)], plasma renin and aldosterone were within normal limits but plasma chromogranin A (Ch A) was elevated (849 ng/ml). Patient underwent EUS of right adrenal gland, which showed enlarged heterogeneous right adrenal gland as shown in [Figure 1]a. EUS FNAC smears from the lesion showed amorphous, homogenous material staining cyanophilic to orangeophilic with papanicolaou stain [Figure 1]b and basophilic with May Grunwald Giemsa stain [Figure 1]b. Inset]. Few interspersed spindle cells were also noted. Ziehl neelsen (ZN) and Grocott-Gomori's methenamine silver (GMS) stains were negative. Cell block revealed similar eosiniophilic, amorphous material [Figure 1]c, which showed positive immunostaining with antibody to serum amyloid associated (SAA) protein [Figure 1]c, Inset]. Congo red stain demonstrated apple green birefringence [Figure 1]d under polarizing light, thus confirming it to be amyloid. Thus, a final diagnosis of reactive systemic amyloidosis (RSA) was rendered. Serum protein electrophoresis did not show M band. His deranged renal functions were attributed to amyloidosis. However, no definite cause of underlying inflammatory condition could be recognized.
Figure 1: (a) EUS image showing heterogeneous, enlarged right adrenal gland. (b) FNAC smears of right adrenal gland showing amorphous, cyanophilic to orangeophilic material with well-defined edges (Pap x400). Inset showing amorphous, basophilic material (MGG ×400). (c) Cell block sections of right adrenal gland showing homogenous, amorphous material (H and E x400). Inset showing positive immunostaining with Serum Amyloid Associated antibody (SAA-IHC x400). (d) Congo red staining showing apple green birefringence under polarized light (x400)

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Subsequently, in view of raised Ch A levels, patient underwent excision of right adrenal mass. Grossly multiple grey brown, soft tissue masses were received measuring 18 × 18 × 10 cm showing areas of hemorrhage and necrosis. Microscopically, amorphous eosinophilic material with areas of necrosis was seen [Figure 2]a and [Figure 2]b. Congo red stain [Figure 2]a (Inset)] and SAA–IHC [Figure 2]b (inset)] was positive. No microorganisms were seen on ZN or GMS stains. Despite exhaustive grossing and evaluation of multiple sections, no tumor cells were identified in the specimen. The case was reported as necrotizing lesion with amyloidosis, right adrenal gland.
Figure 2: Excision biopsy sections of right adrenal gland. (a) Amorphous eosinophilic material with adjacent compressed adrenal gland (arrow) (H and E x200). Inset showing apple green birefringence under polarized light (Congo red x400). (b) Areas of necrosis with neutrophilic infiltrate (H and E, x100). Inset showing positive immunostaining with Serum Amyloid Associated antibody (SAA-IHC x400). Author contribution – AT- concept, data collection, writing, and cytopathologic images. HS—design, collection of data, and writing. NC, RP, and AS—EUS image, collection, and interpretation of data. IM—Histopathologic images and interpretation of data. All authors read, edited, and reviewed the manuscript.

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Adrenal masses can be easily detected using modern imaging modalities like USG, CT, or magnetic resonance imaging (MRI), but these techniques are not sensitive or specific enough to differentiate between benign or malignant masses.[2] EUS FNAC offers a minimally invasive and accurate method for tissue sampling of adrenal gland. However, EUS-FNAC of right adrenal gland is technically difficult due to its retrocaval location and long endoscope position.[3] Limited case reports are published in literature citing EUS FNAC of right adrenal gland.[3]

Moreover, diagnosis of amyloidosis on FNAC is not straightforward in clinically unsuspected cases due to its several morphologic mimics. It appears as smooth, homogenous, glassy, amorphous, flocculent material on cytosmears. Depending on organ involved, it may look like mucus, alveolar proteinosis, colloid, necrosis, or chondroid. Amyloid is likely to be misdiagnosed as necrosis on FNAC smears and it is the nearest differential in adrenal gland. The presence of well-defined margins and flocculent appearance favors amyloid over necrosis.[1] Interspersed spindle cells adds to the confusion by resembling granulomas. However, these connective tissue cells, which are always seen in association with amyloid,[1] lack the slipper shaped nuclei of histiocytes in granulomas. Congo red staining is a highly specific test for confirming amyloid on destained smears and cell block. Few case reports are available in literature where amyloidosis is diagnosed on EUS FNAC.[1]

Amyloidosis is a condition associated with several inherited and inflammatory diseases characterized by extracellular deposition of fibrillar proteins produced by aggregation of misfolded proteins. About 23 different proteins are known to form amyloid fibrils in vivo producing similar structural features but associated with distinct clinical conditions.[4] It is clinically important to recognize different types of amyloid. Amyloid associated (AA), amyloid light chain (AL), and amyloid transthyretin (ATTR) types of amyloid can be differentiated by using specific immunohistochemical (IHC) marker.

RSA is caused by deposition of AA protein due to underlying inflammatory conditions like rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, tuberculosis, etc.

Association of amyloid with neoplastic conditions need to be ruled out in appropriate clinical context.[5] This patient had markedly raised plasma Ch A levels, which raised a suspicion of adrenal tumor. Ch A is synthesized in chromaffin granules of neuroendocrine cells and is found at a concentration of <30 ng/ml in healthy subjects. Elevated levels of Ch A are usually seen in neuroendocrine tumors. However, raised Ch A levels may also be seen in subjects with deranged renal functions due to reduced renal degradation.[6] This could possibly explain raised levels of Ch A in this patient.

This case represents a rare presentation of amyloidosis as right adrenal mass where initial diagnosis was rendered on EUS FNAC. Traditionally, biopsy was considered a gold standard for diagnosis of amyloidosis. However, with the advent of EUS-FNAC, cytopathologists will frequently encounter lesions from deep-seated organs. A high index of suspicion for identifying amyloid is required in clinically unsuspected cases to arrive at correct diagnosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to b'e reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Grover A, Kaur G, Kumar A, Gupta V, Bakshi P, Jain S, et al. Abdominal lymphadenopathy: An interesting and rare case diagnosed on endoscopic ultrasound-guided fine needle aspiration cytology. Cytojournal 2016;13:8.  Back to cited text no. 1
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Martinez M, LeBlanc J, Al-Haddad M, Sherman S, DeWitt J. Role of endoscopic ultrasound fine-needle aspiration evaluating adrenal gland enlargement or mass. World J Nephrol 2014;3:92-100.  Back to cited text no. 2
Sharma R, Ou S, Ullah A, Kaul V. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) of the right adrenal gland. Endoscopy 2012;44:E385-6.  Back to cited text no. 3
Pepys MB. Amyloidosis. Annu Rev Med 2006;57:223-41.  Back to cited text no. 4
Halliday BE, Silverman JF, Finley JL. Fine needle aspiration cytology of amyloid associated with nonneoplastic and malignant lesions. Diagn Cytopathol 1998;18:270-5.  Back to cited text no. 5
Coppolino G, Bolignano D, Rivoli L, Mazza G, Presta P, Fuiano G. Tumor markers and kidney function: A systematic review. Biomed Res Int 2014;2014:1-9.  Back to cited text no. 6

Correspondence Address:
Abha Thakur
Department of Pathology, Medanta-The Medicity, Gurugram, Haryana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_575_19

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