CASE REPORT
The rhabdoid variant of adrenocortical carcinoma-Report of three cases and literature review
Pavithra Ayyanar, Mukund N. Sable, Amit K. Adhya, Manoj K. Das1, Madhabananda Kar2, Pritinanda Mishra
Departments of Pathology and Lab Medicine, ‘Urology, and 2Surgical Oncology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India
Address for correspondence:
Dr. Pritinanda Mishra, Department of Pathology and Lab Medicine, All India Institute of Medical Sciences (AIIMS), Bhubaneswar - 751 019, Odisha, India. E-mail: pathol_pritinanda@aiimsbhubaneswar.edu.in
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.
KEY WORDS: Adrenocortical carcinoma, INII1, rhabdoid variant, SMARCB1
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.
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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.[4-6]
Submitted: 26-May-2021 Revised: 12-Nov-2021
Accepted: 14-Nov-2021 Published: 07-Jun-2022
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How to cite this article: Ayyanar P, Sable MN, Adhya AK, Das MK, Kar M, Mishra P. The rhabdoid variant of adrenocortical carcinoma- Report of three cases and literature review. Indian J Pathol Microbiol 2023;66:627-31.
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 1a and 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 1c]. 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 1b]. Multinucleation, mitotic activity-8 — 10/50 high power field (HPF), necrosis, capsular and sinusoidal invasion were noted. There was no atypical mitosis.
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 1e, f and 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 1f], 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 2a-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 2e] and sarcomatoid pattern [Figure 2f] were also noted.
IHC for INI1: Immunostain for INI1 was performed in all three cases, and it was retained [Figures 1d and h, 2g]. 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.[4-6] Weissferdt A et al.[6] have mentioned the
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| Author, year,[ref] | Age (y) | Sex | Clinical presentation | Tumor Size (cm) | weight (gms) Tumor | Histomorphology | IHC | Diagnosis | Follow up details |
|---|---|---|---|---|---|---|---|---|---|
| Dundr P, et al., 2006,[4] | 16 | F | Primary aldosteronism | 3 | 24 | Rhabdoid cells-50% Cells with eosinophilic cytoplasm (50%), clear cells (<10%) | and a-inhibin; Negative for cytokeratin AE1/AE3, EMA, chromogranin A & S100 MIB-1 <3% Positive for vimentin, Melan A, synaptophysin | ACA with rhabdoid features | 16 months, no recurrence |
| Lou E, et al., 2009,[5] | 57 | M | Marked leucocytosis with leukemoid reaction, elevated serum G-CSF | 5.5 | NM | NM | Positive for CD10, PanCK (globular, perinuclear pattern), vimentin, G-CSF & INI1; Negative for EMA, chromogranin, synaptophysin, calretinin, inhibin, renal cell carcinoma antigen, cytokeratins 5/6 and 7, MART-1, CD30, CD45 & CD138 | differentiation G-CSF-secreting adrenal carcinoma with rhabdoid-like | Expired after eight months of diagnosis |
| Weissferdt A et al., 2013,[6] 3 cases | |||||||||
| Case 1 | 55 | F | Non functioning | 10.5 | NM | Rhabdoid cells-70% | Positive for SRC-1, inhibin, calretinin, melan A, CAM5.2 (focal &weak), antimitochondrial antibodies (focal weak); Negative for HMWCK, chromogranin & Pax8. INI1 expression retained Ki67 is <5% to 10% | Primary rhabdoid ACC | Expired four months after diagnosis |
| Case 2 | 45 | F | Non-functioning | 7 | 154 | Rhabdoid cells-90% | Same findings as above | Primary rhabdoid ACC | Alive without any recurrence after 237 months |
| Case 3 | 47 | F | NM | NM | NM | Rhabdoid cells-90% | Same findings as above | Primary rhabdoid ACC | NM |
| Present study | |||||||||
| 3 cases | |||||||||
| Case 1 | 54 | F | Anorexia-3 months, right sided abdominal pain-20 days | 14 | 917 | 70 | INI1 expression retained | ACC, rhabdoid variant | NA |
| Case 2 | 38 | M | Incidentally detected adrenal mass, hypertension+ | 14.5 | 808 | 50 | Positive for melan A (strong), vimentin (diffuse strong), calretinin, (focally weak), synaptophysin (focally strong), cytokeratin (focally weak); negative for S100; INI1 expression retained | ACC, rhabdoid variant | Alive without disease for five months duration, on chemotherapy |
| Case 3 | 14 | F | Case of rhabdomyosarcoma, left flank swelling for 4 months, Functional (clitoromegaly) | 9.5 | 220 | 65 | INI1 expression retained | ACC, rhabdoid variant | Alive without disease after 24 months of diagnosis |
NM=Not mentioned, NA=Not available, ACC=Adrenocortical carcinoma, ACA=Adrenocortical adenoma, G-CSF=Granulocyte-colony stimulating factors
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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.
It 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.
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 be 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.
Financial support and sponsorship Nil.
Conflicts of interest
There are no conflicts of interest.
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