Adrenocortical Carcinoma with Sarcomatoid and Oncocytic Differentiation—A Rare Case Report with Review of Literature

Introduction: Adrenocortical carcinoma is a rare endocrine malignant neoplasm with an estimated incidence of 0.5–2.0 cases per million per year. It is more common in adults (females) with a peak in the fifth decade of life. 

Case Report: A 35 year old male presented to the emergency department with left abdominal pain, weakness, decreased appetite and weight loss for 2 years and intermittent fever for 5 months. On examination, he was found to have pallor, palpitation and a diffuse, tender, fixed and firm to hard swelling in the left lumbar and iliac region. On histopathological examination, it was diagnosed as Adrenocortical Carcinoma with Sarcomatoid and oncocytic differentiation. Immunohistochemistry confirmed the same.

Conclusion: As Adrenocortical carcinosarcoma is an extremely rare neoplasm with a poor prognosis, accurate diagnosis is of utmost importance. Surgical management is the main modality of treatment.

Introduction

Adrenocortical carcinoma is a rare endocrine malignant neoplasm with an estimated incidence of 0.5–2.0 cases per million per year [1]–[3]. It is more common in adults (females) with a peak in the fifth decade of life. The sarcomatoid variant of ACC was first reported in 1987 by de Krijger et al. [4] Till date 8000 cases of conventional adult ACC, 200 cases of conventional paediatric ACC, 56 oncocytic, 47 myxoid and only 35 sarcomatoid types of adrenocortical carcinosarcoma have been reported in the literature [5]–[17], [29]–[43]. In this case report, we present a very rare case of Adrenocortical Carcinoma with Sarcomatoid and oncocytic differentiation.

Case Report

Case History

35 year old male presented to the emergency department with left abdominal pain, weakness, decreased appetite and weight loss for 2 years. The patient also complained of intermittent fever for last 5 months. On examination, he was found to have pallor, palpitation; and a diffuse swelling was noted in the left lumbar and iliac region. The swelling was tender, fixed and firm to hard in consistency. There was no complaint of sweating, headache, loss of consciousness or abnormal pigmentation. The patient was not a known diabetic or hypertensive. The blood parameters, both haematological and biochemical were found to be within normal limits except decreased haemoglobin. On Ultrasound whole abdomen, he was found to have an adrenal mass. Contrast Enhanced-Magnetic Resonance Imaging of the abdomen revealed the mass to be of neoplastic etiology arising from the adrenal gland with the possible differential diagnoses of Pheochromocytoma and Adrenal cortical carcinoma (Figs. 1A and 1B). Serum Dehydro-epiandrosterone and cortisol levels were within normal limits implying that the adrenal lesion was non-functioning. With the above preoperative analysis, the patient was operated in the Urology Department under General anaesthesia. The mass was excised and sent in formalin to the Department of Pathology of Gauhati Medical College and Hospital for histopathological examination.

Fig. 1. (A and B) T1 & T2 weighted image of CE-MRI abdomen reveal fairly well defined multilobulated heterogeneously enhancing predominant peripherally enhancing left suprarenal lesion with internal necrosis, haemorrhage and non-visualization of left adrenal gland separately suggestive of neoplastic etiology. (C and D) Gross image of the mass as a whole and cut open adrenal gland measuring 17 × 15 × 9 cm³. On cut section, it is encapsulated and solid with variegated appearance containing areas of haemorrhage and necrosis. A uniloculated cyst is noted measuring 6 × 5 cm² containing gelatinous material.

Gross Examination

On Gross examination, we received a specimen of left adrenal mass measuring 17 × 15 × 9 cm³. On cut section, it was encapsulated and solid with variegated appearance containing areas of haemorrhage and necrosis. A uniloculated cyst was noted measuring 6 × 5 cm² containing gelatinous material (Figs. 1C and 1D).

Microscopic Examination

On histopathological examination, the tumour was biphasic with both epithelial and mesenchymal components. The epithelial component consisted of sheets and nests of atypical epithelial cells with moderate to abundant eosinophilic cytoplasm and eccentrically placed hyperchromatic nuclei with prominent nucleoli. The mesenchymal component comprised of sarcomatous change with haphazardly arranged fascicles of atypical spindle cells with moderate to severe pleomorphism. Many bizarre cells and atypical mitotic figures were noted. Cystic degeneration and abundant necrosis were also noted (Figs. 2A and 2B).

Fig. 2. (A) H & E section (200X) showing the mesenchymal component consisting of highly pleomorphic atypical spindle cells with enlarged bizarre nucleus and atypical mitotic figures. (B) H & E section (400X) showing the epithelial component in the upper one fourth and the mesenchymal component in the lower three fourth.

Immunohistochemistry

Immunohistochemistry for inhibin, calretinin and vimentin showed positivity whereas Immunohistochemistry for CK, HepPar1, Chromogranin, Synaptophysin and S100 were negative (Figs. 3A to 3D).

Fig. 3. (A and B) IHC for INHIBIN (400X) showing diffuse positivity. (C) IHC for Calretinin (400X) showing positive cytoplasmic staining in the epithelial component. (D) IHC for Vimentin (100X) showing cytoplasmic positivity.

Discussion

Non-hypersecretory Adrenocortical carcinoma can be diagnosed by local manifestations of tumor growth i.e.; mass and pain, or distant metastases to liver, lung, and bones. Genetic or epigenetic changes in the imprinted 11p15 region, resulting in increases in IGF-II expression is implicated in Beckwith–Wiedemann syndrome [18], an overgrowth disorder characterized by macrosomia, macroglossia, organomegaly, developmental abnormalities and embryonal tumors, such as Wilms’ tumor, Adrenocortical carcinoma [19], neuroblastoma, and hepatoblastoma. ß-catenin mutation has been found in both benign and malignant adrenal neoplasms. Loss of heterozygosity at 11q13 are observed in over 90% of Adrenocortical carcinoma and only 20% of adrenocortical adenomas [20], [21]. Somatic PRKAR1A mutations have been demonstrated in sporadic secreting adrenocortical adenomas [22]. Patients can present with hypersecretion or adrenal mass or metastasis or incidental finding during radiology. Signs of cortisol hypersecretion include centripetal obesity, protein wasting with muscle atrophy, skin thinning and striae, impaired defense against infection, osteoporosis, psychiatric disturbances, diabetes, hypertension, and gonadal dysfunction. Androgen hypersecretion in women causes hirsutism, menstrual abnormalities, infertility, and virilisation (alopecia, deepening of the voice, clitoris hypertrophy). Estrogen excess causes gynecomastia in males. Adrenocortical carcinoma can also secrete mineralocorticoids and steroids precursors.

The differential diagnosis of carcinosarcoma of adrenal gland includes renal cell carcinoma, true sarcoma, large cell lymphoma, malignant peripheral nerve sheath tumour with rhabdomyoblastic features and metastases. Sarcomatoid renal cell carcinoma or hepatocellular carcinoma with sarcomatoid dedifferentiation have a similar morphology to carcinosarcoma; however immunohistochemistry positivity for inhibin, melan A, calretinin and negativity for pan CK, EMA and HepPar1 help to differentiate between the two. Malignant peripheral nerve sheath tumor with rhabdomyoblastic elements (Triton tumor) can be excluded by morphology as well as positivity of S-100 and negativity of Melan-A, synaptophysin, and calretinin. Rhabdomyosarcomas are tumours of childhood. Dedifferentiated liposarcoma can be excluded by the absence of a well differentiated liposarcomatous component. Sarcomatoid Adrenocortical carcinoma has a very poor prognosis with frequent metastases, with the majority of patients dying within 3–12 months after surgical treatment [12], [16]. Surgical management should aim at complete removal. In patients with metastatic or progressive disease, medical treatment is started with mitotane. Tumours localized to the adrenal gland (McFarlane stages 1 and 2) have a better outcome than invasive and metastatic tumours (stages 3 and 4). Younger patients have a better prognosis. Cortisol secreting tumour has been found to be associated with a worse prognosis [23]. High mitotic rate or atypical mitoses is also associated with a worse prognosis [24]. LOH at 17p13 was demonstrated to be an independent variable predictive of recurrence after complete surgical removal of localized adrenocortical tumours [25]. Table I illustrates the review of literature of all diagnosed and reported cases of carcinosarcoma and comparison with our case study.

Table I. Table Illustrating the Review of Literature of all Diagnosed and Reported Cases of Carcinosarcoma and Comparison with our Case Study

Author	Age	Sex	Clinicalpresentation	Endocrinedysfunction	Size(cm)	Weight(gm)	Sarcomatouscomponent	Postoperative timeof death
Okazumi et al. [5]	46	Male	Abdominal distention	No	14	880	Spindle	6 months
Collina et al. [6]	68	Female	Abdominal discomfort	No	11	–	Spindle	6 months
Decorato et al. [7]	42	Female	Abdominal pain	No	19	1400	Rhabdomyosarcoma	7 months
Fischer et al. [8]	29	Female	Virilization, Weight loss	Yes	12.5	610	Rhabdomyosarcoma	8 months
Barksdale et al. [9]	79	Female	Hypertension	Yes	5	199	Osteosarcoma, Chondrosarcoma	NA
Lee et al. [10]	61	Male	Flank pain	Yes	12	–	Spindle	2 days
Chung et al. [29]	48	Female	Abdominal distention	No	–	–	Spindle	3 months post op
Somda et al. [30]	58	Female	Abdominal pain	No	13	760	Leiyomyosarcoma	Normal at 16months follow up
Sturm et al. [11]	31	Male	Abdominal pain	No	12	620	Spindle	3 months
Coli et al. [12]	75	Female	Abdominal pain	No	15	–	Spindle	12 months
Sasaki et al. [14]	45	Male	Abdominal pain	No	17	2974	Rhabdomyosarcoma	3 months
Feng et al. [13]	72	Male	Flank pain	No	–	–	Spindle	–
Bertolini et al. [31]	23	Female	Fatigue	No	14	–	Osteosarcoma	14 months
Thway et al. [15]	45	Male	Abdominal pain	No	24	6500	Pleomorphic rhabdomyosarcoma	11 months
Yan et al. [16]	72	Male	Abdominal mass and pain	No	13	–	Spindle	6 months
Kao et al. [32]	45	Male	Abdominal pain	No	15	760	Spindle	7 months
Mark et al. [17]	58	Male	Abdominal pain	No	12	573	Spindle	Normal at 17months follow up
Shaikh et al. [33]	62	Female	Abdominal pain	No	6.5	55	Spindle	4 months
Wei et al. (2015) [34]	63	Female	Abdominal pain	No	8	–	Spindle	Normal at 1 monthfollow up
Wanis et al. [35]	68	Female	Incidental	No	13	–	Spindle	223 days post op
Wanis et al. [35]	65	Male	Incidental	No	12.8	–	Spindle	Normal at 4 months follow up
Zhu et al. [36]	59	Male	Weight loss	No	5	–	Spindle cell	Normal at 6 months follow up
Ishikawa et al. [26]	69	Female	Malaise	Yes	Right-5.5	Right-20	Spindle	4 months post op
					Left-7	Left-35
Iyidir et al. [37]	53	Female	Abdominal pain	No	Right-9	Right-80	Spindle	1 month
					Left-8.5	Left-NA
Papathomas et al. [38]	55	Male	Abdominal pain	No	16	–	Spindle	4 months
Papathomas et al. [38]	70	Female	Abdominal pain	No	15	–	Osteosarcoma, Spindle	8 months
Papathomas et al. [38]	52	Male	Abdominal pain	No	24	3020	Spindle	4.5 months
Saeger et al. (2017) [39]	53	Female	HTN	Yes	13	–	Spindle	Normal at >6months follow up
Sung et al. [1]	51	Male	Non-specific	No	15	–	Spindle	1.7 months
Gulec et al. [40]	52	Male	Abdominal pain	Yes	14	–	–	1 day post op
Sabrine et al. [27]	27	Female	Abdominal pain	No	12	660	Spindle	Normal at 6 months follow up
Rezwana et al. (2019) [41]	37	Female	Abdominal pain	Yes	10	–	Osteosarcoma	Alive at 5 monthsfollow up
Rachh et al. [42]	78	Female	Back pain	No	Right-4.6	-	Spindle	Within few monthsof diagnosis
					Left-6
Zhang et al. [43]	53	Male	Abdominal pain	No	7.2	–	–	Within 6 monthsof diagnosis
Branham et al. [28]	78	Female	Abdominal mass	No	27	3300	Spindle	7 days post op
Present case study	35	Male	Abdominal pain	No	17	1270	Spindle	At 6 months postop doing well

Conclusion

Adrenocortical carcinosarcoma is an extremely rare neoplasm with a poor prognosis. Surgical management is the main modality of treatment. Accurate diagnosis by thorough sampling, careful histological examination and immunohistochemical investigation are often necessary to confirm the adrenocortical origin and distinguish it from other retroperitoneal sarcomatoid neoplasms. The long term survival of a patient depends on early diagnosis, complete surgical excision and radiotherapy to prevent recurrence.