Imprint cytology of adrenal cortical carcinoma. A valuable surrogate for frozen sections
Takahiko Sakuma MD, PhD1 Chikako Kokubo CT, IAC1
Shinya Koike MD, PhD2
Satoshi Shinohara MD3
1Department of Laboratory Medicine, Atsumi Hospital, Tahara, Aichi, Japan
2Department of Surgery, Atsumi Hospital, Tahara, Aichi, Japan
3Department of Urology, Atsumi Hospital, Tahara, Aichi, Japan
Correspondence
Takahiko Sakuma, Department of Laboratory Medicine, Atsumi Hospital, 1-1 Akaishi, Kanbe, Tahara, Aichi, 441-3415 Japan.
Email: thsakuma@atsumi.jaaikosei.or.jp
KEYWORDS: adrenal, adrenocortical carcinoma, cytology, fine needle aspiration, metaplastic ossification
1 INTRODUCTION
Adrenal cortical carcinoma (ACC) is a rare tumour, and its cytological findings have been described only sporadically. We here report a case of ACC in which imprint cytology played an important role in the diag- nosis. Cytological findings of ACC are shown and the correlation to the histology is discussed.
2 OBSERVATION
A 74-years-old woman presented with right hypochondralgia and subfever. Ultrasonography (US) and blood tests suggested cholecystitis/cholangitis, which was successfully treated with antibi- otics. A 66 × 38 mm-sized asymptomatic tumour was incidentally dis- covered around the upper pole of the left kidney. Calcification foci were scattered within the tumour (not shown). The adrenal endocri- nological functions, both cortical and medullary, remained within nor- mal range. Access to the lesion with fine needle aspiration (FNA) was difficult due to its deep location. Systemic imaging surveys showed no other tumours, so the lesion was clinically diagnosed as a potentially malignant tumour of adrenal origin. The pathologic diagnosis was to be made during the operation with frozen sections. Incision biopsy did not cut well. The sections broke into pieces.
Imprint cytology was made instead and stained for rapid cytodiagnosis. The imprint slides were hypercellular. Numerous atypical cells with marked nuclear/cytoplasmic pleomorphism were seen in a haemorrhagic/necrotic background. The tumour cells had clearly defined cell border, and they showed little mutual adhesion. Anisonucleosis, irregularity of the nuclear membrane, conspicuous large eosinophilic nucleoli, and coarsely clumped chromatin were present. Multinuclear
cells were often seen. Mitotic figures were occasionally observed (Figure 1A-D). These cytological findings suggested a high-grade neo- plasm. According to this positive cytodiagnosis, left adrenalectomy with radical nephrectomy was performed.
Permanent histologic sections of the tumour prepared after decalcifi- cation showed proliferation of atypical cells with clear cytoplasm. Approxi- mately one thirds of the tumour was occupied with a diffuse proliferation of tumour cells (Figure 2). Remaining two thirds showed trabecular pattern covered by thin fibrous connective tissue, which was interpreted as vesti- gial adrenal cortex histology (not shown). In the histologic specimens, N/C ratio was lower and cellular/nuclear atypia was less obvious when com- pared with cytology. Besides necrosis and associated microcalcification, metaplastic ossification was widely observed (Figure 2B). However, nei- ther bone marrow formation nor haematopoietic myeloid cells were seen. This mature bone trabecular formation was thought to be responsible for the failure of frozen sections cutting. Mitotic figures were seen two to five per 10 high power fields (not shown). Capsular invasion (Figure 2C) and venous invasion (Figure 2D) were recognised. Immunohistochemically, synaptophysin and chromogranin A were negative, but CD56 was posi- tively stained (not shown). A histopathologic diagnosis of ACC was rendered.
Despite histologically negative resection margin, hepatic metastasis was detected 4 months after the operation. Mitotane administration could not avert progress of the systemic spread, and the patient died of hepatic failure due to massive liver metastases 13 months after the operation.
3 COMMENT
ACC is uncommon. Its incidence has been reported as one to two in million population.1 As percutaneous access to the lesions is difficult
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(D)
due to its anatomic location; FNA cytologic features of ACC have been only sporadically described. The cytologic features of ACC are summarised as atypical cells with elevated N/C ratio, conspicuous nuclear pleomorphism, irregular nuclear membrane, and vacuolated cytoplasm appear singly or as loose aggregate.2-10 In a series of the cytology of ACC, the common cytologic features diagnostic of ACC were hypercellularity (70% of cases), necrotic debris in the back- ground (70%), moderate to marked nuclear pleomorphism (80%), mitotic figures (90%), and prominent nucleoli (60%). Twenty percent of cases exhibited all five features.3,5,9 Some of these cytologic criteria correspond to the histologic criteria of metastasizing ACC. Weiss11 reported that nine criteria most useful in the characterisa- tion of metastasizing adrenocortical tumours: nuclear atypia, mitosis (5/50 high-power field), atypical mitoses, clear cells, diffuse growth pattern, necrosis, venous/sinusoidal/capsular invasion. Of these, eight (nuclear atypia, clear cells, mitoses, diffuse growth pattern, necrosis, venous/capsular invasion) were seen in our case. Although
cytology is inept in the detection of histologic architecture (assess- ment of proliferation pattern and invasion), nuclear/cytoplasmic atypia, tumour diathesis (necrotic and inflammatory background), and mitosis are well recognised. The abovementioned five cytologic findings3,5,9 are useful in the cytodiagnosis of ACC.
In the adult, major differential diagnoses of FNA cytology obtained from the mass lesions of adrenal include metastatic carcinoma to the adrenal and phaeochromocytoma. As the systemic imaging studies dem- onstrated no other lesions, the possibility of metastatic carcinoma was unlikely in our case. The phaeochromocytoma cells are large and have abundant cytoplasm, and appear as singly or small discohesive groups in a necrotic background. Cellular/nuclear pleomorphism is evident, bi/multinuclei, large nucleoli, and naked nuclei are often observed. The chromatin pattern is granular, and sometimes, salt and pepper-like. Ganglion-like cells with giant nuclei with abundant cytoplasm are seen.12 While these cytologic characteristics may be useful in the differential diagnosis of phaeochromocytoma, a minimum invasive procedure even
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(B)
for diagnostic purpose such as FNA should be discouraged because it would invoke an abrupt rise of blood pressure,12,13 which may be seri- ous.13 Phaeochromocytoma is usually symptomatic, and laboratory tests of serum and urine often provide diagnostic results. When pha- eochromocytoma is suspected, clinical diagnosis should be prioritised.
Our case was unique in that ectopic bone formation was preva- lent. While ossification in cancer is occasionally seen such as in meta- plastic carcinoma of the breast, mature bone formation in the adrenal tumour is very rare. In English literature, only a single case of ACC with histologically proven fully developed mature ossification is described.14 A case of adrenal adenoma associated with metaplastic bone formation is also known.15 Tumour necrosis and subsequent microcalcification were likely the cause of ossification. Although rare, we should be aware that calcification and ossification can occur in the adrenal gland tumours, and it may disrupt the preparation of frozen sections. Rapid diagnosis using imprint cytology is an ancillary yet use- ful diagnostic method along with frozen sections.16,17 Also, rapid
cytologic evaluation of smear slides can be employed when histologic samples cannot be procured.18
FNA of the adrenal lesions has been performed under imaging guid- ance utilising computed tomography (CT)/US3,5,9 or fluorography.3 CT is expensive equipment and is not universally available. Furthermore, percu- taneous approach would limit the depth of the lesion reachable. With the advent of US probes that can be used with digestive endoscopy, FNA of the adrenal lesions via transgastric/enteric approach has become avail- able.19,20 This method facilitates the access to adrenal lesions and expands the feasibility of cytopathologic examination. In our case, nuclear/cellular atypia is better recognised in the cytology slides than histology. The cyto- logic and histologic images presented here would be informative for the cytotechnicians/cytopathologists in the cytodiagnosis of ACC.
CONFLICT OF INTEREST
The authors declare no potential conflict of interest.
ORCID
Takahiko Sakuma (D https://orcid.org/0000-0002-9477-2196
REFERENCES
1. Correa P, Chen VW. Endocrine gland cancer. Cancer. 1995;75(suppl 1): 338-352. https://doi.org/10.1002/1097-0142(19950101)75:1+<338: AID-CNCR2820751316>3.0.CO;2-F.
2. Levin NP. Fine needle aspiration and histology of adrenal cortical car- cinoma: a case report. Acta Cytol. 1981;25:421-426.
3. Katz RL, Patel S, Mackay B, Zornoza J. Fine needle aspiration cytology of the adrenal gland. Acta Cytol. 1984;28:269-282.
4. Cochand-Priollet B, Jacquenod P, Warnet A, Ferrand J, Galian A. Adrenal cortical carcinoma: a case diagnosed by fine needle aspiration cytology. Acta Cytol. 1988;32:128-130.
5. Saboorian MH, Katz RL, Charnsangavej C. Fine needle aspiration cytology of primary and metastatic lesions of the adrenal gland. A series of 188 biopsies with radiologic correlation. Acta Cytol. 1995; 39:843-851.
6. Sasano H, Shizawa S, Nagura H. Adrenocortical cytopathology. Am J Clin Pathol. 1995;104:161-166. https://doi.org/10.1093/ajcp/ 104.2.161.
7. Sharma S, Singh R, Verma K. Cytomorphology of adrenocortical carci- noma and comparison with renal cell carcinoma. Acta Cytol. 1997;41: 385-392. https://doi.org/10.1159/000332529.
8. Krishnamurthy S, Ordóñez NG, Shelton TO, Ayala AG, Sneige N. Fine- needle aspiration cytology of a case of oncocytic adrenocortical carcinoma. Diagn Cytopathol. 2000;22:299-303. https://doi.org/10.1002/(SICI)1097- 0339(200005)22:5<299:AID-DC8>3.0.CO;2-5.
9. Ren R, Guo M, Sneige N, Moran CA, Gong Y. Fine-needle aspiration of adrenal cortical carcinoma: cytologic spectrum and diagnostic chal- lenges. Am J Clin Pathol. 2006;126:389-398. https://doi.org/10. 1309/AQFEB5WEMU41N9K1.
10. Kanjilal B, Ghosh M, Mitra A, et al. Cytological diagnosis of adrenocorti- cal carcinoma: a report of 2 cases in children. Diagn Cytopathol. 2018;46: 1064-1067. https://doi.org/10.1002/dc.24056.
11. Weiss LM. Comparative histologic study of 43 metastasizing and nonmetastasizing aderenocortical tumors. Am J Surg Pathol. 1984;8: 163-169.
12. Jiménez-Heffernan JA, Vicandi B, López-Ferrer P, González- Peramato P, Pérez-Campos A, Viguer JM. Cytologic features of pheo- chromocytoma and retroperitoneal paraganglioma. A morphologic and immunohistochemical study of 13 cases. Acta Cytol. 2006;50: 372-378. https://doi.org/10.1159/000325975.
13. McCorkell SJ, Niles NL. Fine-needle aspiration of catecholamine- producing adrenal masses: a possibly fatal mistake. AJR Am J Roentgenol. 1985;145:113-114. https://doi.org/10.2214/AJR.145.1.113.
14. Lack EE. Adrenal cortical carcinoma. AFIP Atlas of Tumor Pathology. Fourth Series, Fascicle 8. Tumor of the Adrenal Glands and Extraadrenal Paraganglia. Washington DC: American Registry of Pathology; 2007:131-160.
15. Masugi Y, Kameyama K, Aiba M, et al. Non-functional adrenocortical adenoma with extensive degeneration. Pathol Int. 2003;53:241-245. https://doi.org/10.1046/j.1320-5463.2003.01462.x.
16. Kim K, Phillips ER, Paolino M. Intraoperative imprint cytology: its sig- nificance as a diagnostic adjunct. Diagn Cytopathol. 1990;6:304-307. https://doi.org/10.1002/dc.2840060503.
17. Scopa CD, Melachrinou M, Apessou D, Bonikos D. Tissue imprints in surgical pathology: a rapid intraoperative diagnostic aid. Diagn Cytopathol. 1990;6:5-8. https://doi.org/10.1002/dc.2840060103.
18. Sakuma T, Iseki R, Mimura A, Tanigawa M, Takamizu R. Rapid cytologic diagnosis of choroidal malignant melanoma from vitreous smear. J Fr Ophthalmol. 2012;35:535.e1-e4. https://doi.org/10.1016/j.jfo.2011. 08.009.
19. Stelow EB, Debol ST, Stanley MW, Mallery S, Lai R, Bardales RH. Sampling of the adrenal glands by endoscopic ultrasound-guided fine- needle aspiration. Diagn Cytopathol. 2005;33:26-30. https://doi.org/ 10.1002/dc.20273.
20. Sisman G, Erzin YZ, Senturk H. Diagnosis of adrenocortical carcinoma via endosonography-assisted fine-needle aspiration of inferior vena cava thrombosis: fist case in the literature. Dig Endosc. 2013;25:338- 339. https://doi.org/10.1111/den.12028.
How to cite this article: Sakuma T, Kokubo C, Koike S, Shinohara S. Imprint cytology of adrenal cortical carcinoma. A valuable surrogate for frozen sections. Diagnostic Cytopathology. 2019;1-4. https://doi.org/10.1002/dc.24295