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BRIEF REPORT
Cytological diagnosis of adrenocortical carcinoma: A report of 2 cases in children
Banhisikha Kanjilal1 | Moupali Ghosh1 | Avijit Mitra2 | Suvrendu Kar3 | Janki Bisht2 | Ram Narayan Das1 | Uttara Chatterjee1
1Department of Pathology, IPGME&R, Kolkata, India
2Department of Pediatric Surgery, IPGME&R, Kolkata, India
3Department of Endocrinology, IPGME&R, Kolkata, India
Correspondence
Uttara Chatterjee, Department of Pathology, IPGME&R, 57/11A, Ballygunje Circular Road, Kolkata 700019, West Bengal, India. Email: uttarac1@gmail.com
Adrenocortical carcinoma (ACC) is a rare tumour, which sometimes affects pediatric age group. Fine needle aspiration cytology (FNAC) is a rarely performed technique in adrenal cortical tumours. There is sparse literature available describing the cytological findings of ACCs in children. Here we describe the cytological findings of 2 cases of ACCs in children. The first case describes the FNAC findings in a 4 year old girl who presented with a large abdominal mass. The second case narrates the intra-operative imprint cytology findings in a 2-year-old boy who came with precocious puberty. However, diagnosis of adrenocortical tumours based on cytology alone can be difficult and definitive diagnosis should be made after correlating cytological features with the clinical profile, radiology, histopathology, and immunohistochemistry.
KEYWORDS
adrenocortical tumours, FNAC, imprint cytology, pediatric age group
1 INTRODUCTION
Adrenocortical carcinoma (ACC) is an unusual tumour, which seldom affects pediatric age group. They comprise about 0.2% of all pediatric solid tumours. Around 0.2-0.3 new cases of ACC are reported per 1 million children per year.1-3 In the paediatric age group, most of the adrenal tumours are associated with endocrine symptoms and diagno- sis is based mainly on radiological and biochemical work-up. Fine needle aspiration cytology (FNAC) is a rarely performed procedure for adrenocortical neoplasms.
Here we describe the cytological findings of 2 cases of ACCs in children. The first case describes the FNAC findings of a 4-year-old girl who presented with a large abdominal mass. The second case narrates the intra-operative imprint cytology findings in a 2-yearold boy who came with precocious puberty.
2 CASE 1
A 4-year-old girl presented with a rapidly enlarging abdominal mass. Contrast-enhanced computed tomography (CECT) showed a large structure involving the adrenal without any evidence of calcification (Figure 1A). On examination, she was found to be hypertensive. Urinary vanilylmandlic acid levels were normal. She was also found to have Cushing’s syndrome. Ultra-sound guided FNAC was done which
showed hypercellular smears composed of sheets and clusters of large cells with abundant finely granular cytoplasm, eccentrically placed vesic- ular nuclei, prominent nucleoli, and evidence of nuclear pleomorphism. Several binucleate cells and bizarre giant cells were present (Figure 1B- E). The possibility of an adrenocortical tumour was considered. The sec- tions of the cell block showed thick trabeculae of cells with abundant granular eosinophilic cytoplasm (Figure 1F). Immunohistochemistry performed on the cell block showed diffuse and strong positivity for vimentin. It was also positive for Inhibin (Figure 1F). It was negative for NSE, chromogranin, and synaptophysin, thereby confirming the diagno- sis of adrenocortical tumour, possibly carcinoma. She underwent excision of the tumour which showed features of an ACC, with evidence of vascular and capsular invasion. She was further treated with chemotherapy. However, in spite of the treatment, she developed pul- monary metastasis and passed away 2 months after surgery.
3 CASE 2
A 2-year-old boy presented to pediatric surgery out patients’ depart- ment with precocious puberty and remarkable increase in muscle strength. Laboratory investigations showed increased levels of dehy- droepiandrosterone sulphate 777 µg/dL (normal 22-184 µg/dL) and serum testosterone 107.02 nmol/L (normal 4-7 nmol/L). Whereas serum beta HCG <0.6 mIU/mL (normal 5 mIU/mL) and plasma ACTH
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levels 2.03 pg/mL (10-50 pg/mL, 8 AM) were decreased. Level of serum cortisol was 9.4 mcg/100 mL (normal 8 AM: 3-21 mcg/dL), and serum 17-OH progesterone was 11.60 ng/ml (normal <1.0 ng/mL). CECT of the whole abdomen showed a well-circumscribed lobulated, heterogeneously enhancing retroperitoneal space occupying lesion, 5 cm in diamteter with intralesional calcification possibly arising from the adrenal (Figure 2A). These findings suggested a hormonally active, androgen secreting tumour. The child was posted for surgery and the entire mass was removed. Macroscopically the tumour was soft, yel- low brown with areas of necrosis and haemorrhage (Figure 2B). Imprint smears were taken and cytological examination revealed a population of large polygonal cells, with vacuolated cytoplasm, irregu- lar nuclei with prominent nucleoli and perinuclear halo. The cells had plentiful granular cytoplasm. A few mitotic figures and bare nuclei were also observed (Figure 2C-F). The features were suggestive of an adrenocortical neoplasm, possibly carcinoma. No evidence of extra-adrenal extension was noted during surgery. The histology of the specimen showed features of ACC with presence of necrosis,
broad bands of fibrosis, increased mitotic figures and capsular invasion. The patient was treated with adjuvant chemotherapy with Mitotane. During the post-operative period there was atrophy of limb muscles. The child is doing very well on a 2 years follow-up.
4 | DISCUSSION
Adrenal cortical tumours are unusual tumours, especially in the paedi- atric age group, where they form 0.2% of all paediatric solid tumours.1-3 FNAC is the first and foremost line of investigation in paediatric intra-abdominal masses in our practice. The most common paediatric intra-abdominal tumours are Wilms tumour and neuroblas- toma followed by germ cell tumours, rhabdomyosarcoma, clear cell sarcoma of kidney, hepatoblastoma, lymphomas and primitive neu- roectodermal tumours. Although, the cytological diagnosis of Wilms tumour and neuroblastoma are usually straightforward, the other less common ones can pose considerable diagnostic challenge. Precise
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preoperative diagnosis and categorisation of tumours is important so that specific neo-adjuvant chemotherapy can be given and also to avoid chemotherapy in tumours where it is not recommended.
Amongst adrenal tumours in children, the commonest one is neu- roblastoma which typically shows small round cell morphology with varying amounts of neuropil and ganglionic differentiation. Adrenal cortical tumours are rare, most of them are of endocrinologically active in the paediatric age group. Hence, FNAC is rarely performed. Intraoperative touch imprint cytology is a valuable tool for deep seated retroperitoneal sites inaccessible for FNAC. In case of intrao- perative diagnosis of a malignant lesion, metastatic work up and addi- tional treatment modalities can be planned. Cytological findings of ACCs in children, has not been described earlier. It is important to familiarise ourselves with the cytological features of these tumours for appropriate management.
There are only a handful of reports describing cytological features of adrenocortical tumours.4-6 The smears from adrenal carcinomas are usually quite cellular and consist of cells arranged singly or in large clusters. The cells are usually polygonal epithelial cells with plentiful
finely granular cytoplasm. Some of the cells have abundant fragile cytoplasm, sometimes with vacuolation. Numerous bare nuclei can be there in the background along with necrosis. Thin blood vessels are sometimes seen to traverse the cell and tissue clusters. The nuclei are eccentric with marked nuclear pleomorphism, nucleomegaly, hyper- chromasia, coarse chromatin and multiple, prominent nucleoli. Adrenal cortical carcinomas show overtly malignant, bizarre tumour cells, mul- tinucleated tumour giant cells with vesicular nuclei and macronucloli in substantial amounts, resembling poorly differentiated carcinomas. Mitotic figures including atypical forms are easily detected in adrenal carcinomas.7,8 The largest series so far is by Ren et al.,5 reported on a series of 19 cases, with ages ranging from 34 to 68 years. They con- clude that cytological, clinical, radiological, and immunohistochemical correlation together is important for arriving at a correct diagnosis. IHC performed on cell block, if available, is a useful tool for confirming adrenocortical origin.
The common cytological differential diagnosis of ACCs are renal cell carcinomas (RCCs), including its sarcomatoid variant, phaeochro- mocytoma, metastatic carcinomas, and melanomas. ACCs usually
show diffuse and strong positivity for vimentin, however it is not spe- cific for adrenal origin. Positivity for Inhibin and calretinin are also considered to be useful. Inhibin, though positive in only about 50% of the cases, is considered to be more specific.5 SF-1 is thought to be a highly sensitive marker of adrenal origin.9 On imaging studies in the paediatric age group, adrenal masses first brings the possibility of neu- roblastoma followed by retroperitoneal germ cell tumours which can also involve the adrenal gland. In infants negativity for chromogranin, neuron specific enolase and CD56 are useful in ruling out neuro- blastma, although most of the times, the morphology alone is fairly characteristic. Synaptophysin is not considered to be a useful immu- nostain as it is sometimes positive in adrenocortical tumours. In case of adults, the same panel rules out pheochromocytoma. Epithelial membrane antigen (EMA) and CD 10 are important in ruling out RCCs, although RCCs are rare in this age group. Translocation associated RCC (t Xp11.2) can be seen in paediatric age group, which shows nuclear positivity for transcrption factor E3 protein.1º Negative stain- ing for HMB-45 is useful in differentiating adrenocortical tumours from metastatic melanomas.
Differentiating benign from malignant adrenocortical tumours is extremely difficult on cytology alone, as architectural pattern including capsular and vascular invasion cannot be evaluated. Tumour size and weight are also not available for cytologic evaluation, which are impor- tant criteria in evaluation of paediatric adrenal cortical neoplasms.11,12 In an effort to distinguish carcinomas from adenomas, Ren et al.5 observed that smears from adrenocortical adenomas tended to show more cohesive clusters with several bare nuclei. They evaluated 5 cyto- logic criteria, comprising necrosis, hypercellularity, moderate to marked nuclear pleomorphism, mitotic figures and prominent nucleoli, amongst which they found that necrosis and mitosis were most often present in carcinomas. Features like focal nuclear atypia and anisonucleosis can be found in adrenal adenomas as well. Benign and malignant tumours can- not always be distinguished reliably on cytology only.13,14 Radiological imaging also cannot reliably distinguish benign from malignant. Even after detailed histopathological examination, it can be quite difficult at times to distinguish adrenocortical tumours (ACTs) using the Weiss cri- teria alone, especially in the paediatric age group. The Weiss criteria, in the paediatric age group often leads to overdiagnosis of malignanacy.11 Quite recently, another set of criteria, the Wieneke’s criteria, has been advocated for categorisation of paediatric adrenocortical tumours.12,15 We have in the past, validated the usefulness of Weineke’s criteria in differentiating benign from malignant adrenocortical neoplasms in the paediatric age group.16,17 Cytological features such as atypia, nuclear pleomorphism, clear cytoplasm, mitosis including atypical forms are not sufficient in differentiating benign from malignant neoplasms.11,12
5 CONCLUSION
Here we describe the FNAC and imprint cytological findings of 2 cases of ACCs in children. A careful and integrated assessment of clinical, radiological and cytological features along with immunohistochemistry on cell block can be helpful in the diagnosis and categorisation of these tumours.
CONFLICT OF INTEREST
The authors declare that they have no conflicts of interest with the contents of this article.
ORCID
Uttara Chatterjee D https://orcid.org/0000-0002-9346-1695
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How to cite this article: Kanjilal B, Ghosh M, Mitra A, et al. Cytological diagnosis of adrenocortical carcinoma: A report of 2 cases in children. Diagnostic Cytopathology. 2018;46: 1064-1067. https://doi.org/10.1002/dc.24056