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Abstract
Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. Extensive rhabdoid morphology in ACC has been described recently in very few cases. The proportion of rhabdoid morphology and the role of SMARCB1/ INI1 expression in these tumor cells to diagnose the specific variant is not described in the literature. We reviewed the clinicopathological features of nine cases of adrenocortical neoplasm. Out of which, three cases of ACC showed predominant rhabdoid morphology. Large discohesive cells with abundant cytoplasm containing eosinophilic inclusions, eccentric vesicular nucleus, and prominent nucleoli. INI1 immunostain was retained in all cases. We reported the rhabdoid variant of ACC, a novel entity, and its diagnostic approach from their histological mimickers. Identifying more cases of this entity will help to clearly understand the pathogenesis, biologic behaviour, and any specific molecular alterations in the future.
Keywords: Adrenocortical carcinoma, INII1, rhabdoid variant, SMARCB1
How to cite this article: Introduction 
Adrenocortical carcinoma (ACC) is a primary tumor arising from the adrenal cortex. It has three variants (oncocytic, myxoid, and sarcomatoid).[1] The Rhabdoid variant/rhabdoid features in adrenocortical neoplasms is an uncommon and recently described entity.
A malignant rhabdoid tumor (MRT) was initially reported in the pediatric kidney. Histopathological features include discohesive tumor cells arranged in sheets, abundant cytoplasm containing eosinophilic inclusions, eccentrically placed round nucleus with a prominent nucleolus. Extra-renal MRT includes atypical teratoid/rhabdoid tumor [AT/RT], tumors located in the soft tissue, lung, esophagus, etc. Poorly and undifferentiated carcinoma will show rhabdoid morphology. However, the cut-off of rhabdoid morphology to consider it as a specific variant has not been mentioned in the literature.[2]
SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1)/INI1 (Integrase interactor 1) deficient tumors are characterized by the inactivation of the SMARCB1 gene by mutations. Although this group of malignant tumors tends to show rhabdoid morphology, INI1 inactivation has also been reported in epithelioid sarcoma, renal medullary carcinoma, epithelioid malignant peripheral nerve sheath tumor, and sinonasal basaloid carcinoma.[3] The role of INI1 expression by molecular or immunohistochemistry (IHC) method in malignant rhabdoid tumors and tumors with rhabdoid morphology is not clearly documented. Rhabdoid morphology/differentiation indicates clinically aggressive behaviour and needs proper management and follow-up.
We report three cases of a rhabdoid variant of ACC, and a diagnostic approach. Only five cases of adrenocortical neoplasms have been reported to date.[4],[5],[6]
Case Details Case 1
A 54-year-old female patient presented with anorexia, abdominal pain for 20 days, and incidentally detected right suprarenal mass. Right-sided adrenalectomy was done. Grossly a single encapsulated solid gray-brown mass weighing about 917 grams and measuring 14 cm in greatest dimension. Microscopic examination revealed two morphological types of tumor cells arranged in solid sheets and nests [Figure 1]a and [Figure 1]b. One group of morphology is arranged in discohesive cells in sheets; these were large cells with abundant cytoplasm containing eosinophilic hyaline inclusion, eccentrically placed round to oval vesicular nucleus and prominent nucleoli [Figure 1]c. This morphology was seen in 70% of the total tumor area. The other tumor morphology was sheets of large cells with abundant cytoplasm containing vacuolar and granular appearance resembling “spider cells” and also showed eosinophilic hyaline inclusions, central and eccentrically placed vesicular nucleus, and large intranuclear inclusion like nucleoli, which were PAS negative [Figure 1]b. Multinucleation, mitotic activity-8--10/50 high power field (HPF), necrosis, capsular and sinusoidal invasion were noted. There was no atypical mitosis.
Figure 1: (a) The histomorphology of case 1- ACC, rhabdoid variant showing diffuse sheets of two types of morphology (Hematoxylin and Eosin, 100x); (b) The other morphology of tumor cells containing abundant cytoplasm with peripheral vacuolization as well as eosinophilic cytoplasmic inclusion, a moderate degree of nuclear pleomorphism, eccentrically placed vesicular nucleus and large prominent inclusion like nucleoli (arrow) (Hematoxylin and Eosin, 200x); Inset showed large intranuclear inclusions (arrow) were PAS negative (Periodic Acid Schiff, 400x); (c) sheets of discohesive tumor cells (rhabdoid morphology) with abundant eosinophilic cytoplasm and a moderate degree of cellular pleomorphism, large intranuclear cytoplasmic inclusions (Hematoxylin and Eosin, 200x, 400x); (d) retained INI1 expression in tumor cells (immunostain, 200x); (e) The histomorphology of case 2- ACC, sheets of tumor cells showing rhabdoid morphology (Hematoxylin and Eosin, 100x); (f) discohesive tumor cells with high mitotic activity, atypical mitotic figure (arrow), a moderate degree of cellular pleomorphism (Hematoxylin and Eosin, 400x); (g) Along with these tumor cells and few spider cells (arrow) (Hematoxylin and Eosin, 200x); 1h) retained INI1 expression in tumor cells (immunostain, 400x)Case 2
A 14-year-old female patient presented abdominal distention involving the left flank region for four months and had a left thigh mass. The thigh mass was diagnosed as rhabdomyosarcoma, and she had a left adrenal mass. She underwent excision of the left adrenal mass. Gross examination showed a single encapsulated gray-brown solid mass weighing about 220 grams and measuring 9.5 cm in greatest dimension. Microscopic examination showed similar morphology as described in case 1 [Figure 1]e, [Figure 1]f and [Figure 1]g. This morphology was comprised 50% of the total tumor area. The other morphology of tumor was nests of cohestive cells, mitotic activity-12-15/50HPF, atypical mitotic figures [Figure 1]f, necrosis, capsular, and lymphovascular invasion.
Case 3
A 38-year-old male patient presented with incidentally detected left adrenal mass and had hypertension. Excision of the mass showed a gray-brown solid mass weighing about 808 grams and measuring 14.5 cm in the greatest dimension. Microscopic examination showed an encapsulated tumor arranged predominantly in solid sheets and lobules with similar morphology as described in case 1 & 2 [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d. This morphology was seen in 65% of the total tumor area. The mitotic count was 20/50HPF. Atypical mitotic figures, necrosis, capsular invasion were absent. No lymphovascular invasion. Focal areas of alveolar pattern containing haemorrhage [Figure 2]e and sarcomatoid pattern [Figure 2]f were also noted.
Figure 2: (a) The histomorphology of case 3 -ACC, rhabdoid variant showing tumor with peripheral normal adrenal parenchyma (arrow) (Hematoxylin and Eosin, 20x); (b& c) sheets of rhabdoid cells with a moderate degree of cellular pleomorphism (Hematoxylin and Eosin, 200x); (d) tumor cells with eosinophilic cytoplasmic inclusions (Hematoxylin and Eosin, 20x); (e) alveolar pattern of rhabdoid tumor cells (Hematoxylin and Eosin, 200x); (f) focal sarcomatoid pattern (Hematoxylin and Eosin, 200x); (g) retained INI1 expression in tumor cells (immunostain, 400x)IHC for INI1: Immunostain for INI1 was performed in all three cases, and it was retained [Figure 1]d and [Figure 1]h, [Figure 2]g. We reported as ACC, rhabdoid variant.
Follow-up
The first case was lost follow-up; the second and third cases were alive without recurrence after 24 months and five months after the diagnosis.
Discussion We reviewed the clinicopathological features of reported cases, shown in [Table 1].[4],[5],[6] Weissferdt A et al.[6] have mentioned the rhabdoid areas in 70–90% of the tumor mass. We had noticed rhabdoid morphology comprising 70%, 50%, and 65% of the tumor mass in three cases, respectively. We compared the other features of reported cases, the similarities noted in age, sex, and functional clinical presentation. Tumor size and weight are significantly large in our cases compared to the previous cases.
Table 1: Clinicopathological review of adrenocortical tumors with rhabdoid features/variantIt is important to identify this entity from the histologic mimickers, which include MRT, the oncocytic variant of ACC, rhabdoid renal cell carcinoma, and rhabdomyosarcoma. MRT shows classical morphology, cytoplasmic inclusions, and loss of INI1 expression.[2] This finding will help to differentiate it from the malignant rhabdoid tumor of the kidney in the pediatric population. Oncocytic tumors will show abundant granular eosinophilic cytoplasm with a centrally placed nucleus containing mitochondria. Immunostain for antimitochondrial antibody indicates oncocytic differentiation.[7] We did not have the antimitochondrial antibody. Hence it was not performed. Application of Weiss score for determining malignant in the rhabdoid variant is yet to be studied as only very few cases have been reported. Renal cell carcinoma will show conventional morphology and positive immunostaining for PAX8 and CD10.
Rhabdoid morphology of carcinoma (of different sites) was compared with INI1 immunoexpression in a few studies. Kinoshita F et al.[8] noted that SMARCB1 expression was intact in 96% cases of renal cell carcinoma with rhabdoid features. Retained INI1 expression was reported in three undifferentiated and three dedifferentiated endometrial carcinomas with rhabdoid morphology.[9] Undifferentiated malignant tumors with rhabdoid phenotype showed retained INI1.[10] Most of these rhabdoid morphology tumors showed loss of SMARCA4. Although rhabdoid morphology is commonly associated with INI1 deficiency, it does not always show loss of INI1. The rhabdoid morphology extends its pathological alteration to other core subunits of SWI/SNF deficient family tumors, especially SMARCA4.
We conclude that rhabdoid variant of ACC is a recently described entity. Immunostain for INI1 will be retained in these tumors. A proper clinicopathological and immunohistochemical features approach towards a correct diagnosis.
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References 
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CheckDOI: 10.4103/ijpm.ijpm_515_21
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