Journal of Cytology
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CASE REPORT  
Year : 2014  |  Volume : 31  |  Issue : 2  |  Page : 111-113
Cytodiagnosis of myxoid adrenocortical carcinoma and role of immunocytochemistry to differentiate it from renal cell carcinoma


Department of Pathology, Medical College, Kolkata, West Bengal, India

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Date of Web Publication14-Aug-2014
 

   Abstract 

Adrenocortical carcinoma (ACC) is a rare malignancy and cytodiagnosis of this tumor is not routinely encountered by a cytopathologist. Here, we report a case of ACC initially diagnosed by computed tomography (CT)-guided fine needle aspiration cytology (FNAC) with the help of immunocytochemistry. A 48-year-old lady presented with flank pain and abdominal mass for the last 6 months. A CT scan of her abdomen revealed a large mass arising from the upper part of the left kidney. CT-guided FNAC was performed. Cytologic smears showed pleomorphic large cells arranged discretely and in small aggregates against a myxoid background. The cells had a high nucleocytoplasmic ratio, anisonucleosis and conspicuous nucleoli. Based on cytomorphology, differential diagnoses of ACC and renal cell carcinoma (RCC) were made. On immunocytochemistry, the tumor cells were synaptophysin, inhibin, vimentin and Melan-A positive but cytokeratin and epithelial membrane antigen negative. Thus, a cytodiagnosis of myxoid ACC was made and histopathologic examination was suggested. Subsequent histologic examination and immunohistochemistry proved the case to be myxoid ACC.

Keywords: Adrenocortical carcinoma; cytodiagnosis; immunocytochemistry

How to cite this article:
Mondal SK, Dasgupta S, Mandal PK, Sinha MG. Cytodiagnosis of myxoid adrenocortical carcinoma and role of immunocytochemistry to differentiate it from renal cell carcinoma. J Cytol 2014;31:111-3

How to cite this URL:
Mondal SK, Dasgupta S, Mandal PK, Sinha MG. Cytodiagnosis of myxoid adrenocortical carcinoma and role of immunocytochemistry to differentiate it from renal cell carcinoma. J Cytol [serial online] 2014 [cited 2021 Sep 17];31:111-3. Available from: https://www.jcytol.org/text.asp?2014/31/2/111/138689



   Introduction Top


Adrenocortical carcinoma (ACC) is a rare malignant tumor with an incidence of one to two cases per million per year. [1] Cytodiagnosis of this tumor is not routinely encountered by a cytopathologist. Imaging studies can easily and precisely visualize intra-abdominal mass lesions and computed tomography (CT)-guided fine needle aspiration cytology (FNAC) may be used for early confirmation and exclusion of neoplastic diseases in cases presenting with intra-abdominal masses. FNAC is a safe and accurate tool in the diagnostic characterization of adrenal masses. [2] The morphologic distinction of ACC from renal cell carcinoma (RCC) in FNA material is not always feasible based on cytology alone. To date, the immunohistochemical distinction of ACC from RCC is based on a panel of antibodies that include vimentin, cytokeratins and epithelial membrane antigen (EMA). [3]


   Case Report Top


A 48-year-old lady presented with flank pain and abdominal mass for the last 6 months. The patient had good general health with stable vitals.

The hematologic parameters were within normal limits. CT of the abdomen showed a large mass arising from the upper part of the left kidney. The mass had a variegated appearance. CT-guided FNAC was performed. Cytologic smears showed pleomorphic large cells arranged discretely and in small aggregates against a myxoid background. The cells had a high nucleocytoplasmic ratio along with anisonucleosis. In some nuclei, conspicuous nucleoli were present [Figure 1]a. Based on cytomorphology, differential diagnoses of ACC and RCC were made.
Figure 1: (a) Cytologic smears showed pleomorphic large cells arranged discretely and in small aggregates against a myxoid background. The cells have a high nucleocytoplasmic ratio, anisonucleosis and conspicuous nucleoli (MGG, ×400). (b) Immunocytochemistry-vimentin positive tumor cells. (c) Gross appearance of the adrenocortical carcinoma: The cut-section showed that the tumor had a variegated appearance with myxoid areas. (d) Histology showing an encapsulated tumor with myxoid areas (H and E, ×100)

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Immunocytochemistry was performed with a panel of antibodies. The tumor cells were found to be positive for synaptophysin, inhibin, vimentin and Melan-A [Figure 1]b. The tumor cells were negative for cytokeratin and EMA. A cytodiagnosis of myxoid ACC was made based on clinicoradiological, morphologic and immunocytochemical results.

Subsequently, the patient underwent resection of the tumor and histopathologic examination was carried out. Gross examination revealed that the tumor had a diameter of 7.5 cm and that it weighed 543 g. The cut-section showed that the tumor had a variegated appearance with myxoid areas [Figure 1]c. Microscopic examination showed a capsulated tumor composed of large cells with a high nucleocytoplasmic ratio, pleomorphic nuclei and prominent nucleoli. The cells were arranged in sheets. Myxoid areas were present [Figure 1]d. Immunohistochemical analysis was performed with the same panel of markers used for immunocytochemistry and similar results were obtained. After correlation with all the above features, a final diagnosis of myxoid ACC was established.

The patient is on 6 months of follow-up, which is uneventful.


   Discussion Top


The adrenal gland has become a frequent target of FNAC with the availability of sensitive imaging techniques and better localization. Currently, FNAC is the only non-surgical means of obtaining a diagnosis in a patient with adrenal mass. [4]

The FNA specimens from adrenal tumors are usually cellular and show tumor cells in a lipid-rich background (best seen in Diff-Quik-stained slides). The individual cells display central or eccentrically placed nuclei with evenly dispersed chromatin and small nucleoli. The cytoplasm is usually foamy and ill defined, and a majority of cells can appear as stripped nuclei. The cells can occur as large cohesive fragments or singly scattered cells; some specimens can show mostly singly scattered cells, which can occur as a function of smearing technique or in large adrenal tumors with necrosis. [2],[5],[6]

It is a challenge in cytology practice to differentiate between aspirates from RCC and adrenocortical tumors. Specimens from RCC usually lack a lipid-rich background; however, it is important to obtain enough material for immunostains to differentiate between these two entities. [7]

In our case, the cytologic smears showed pleomorphic large cells arranged discretely and in small aggregates against a myxoid background. The cells had a high nucleocytoplasmic ratio along with anisonucleosis and conspicuous nucleoli. Based on these findings, differential diagnoses of ACC and RCC were given.

Immunohistochemically, strong positivity for cytokeratin, EMA, CD10 and Lewis blood group isoantigen favors RCC, whereas positivity for inhibin, A103, Melan-A and synaptophysin favors ACC. [8] On histologic samples, it is generally found that ACC displays immunoreactivity for vimentin but not for EMA, whereas RCC is often immunoreactive with EMA but negative for vimentin. [9],[10] Alfa-inhibin antibody shows an intense and specific immunostaining pattern for cells of adrenal origin, even in paucicellular samples, and there is a scope for widespread clinical utility of this marker by cytopathologists. [3]

We performed immunocytochemical analysis with a panel of markers. The tumor cells, in our case, were found to be positive for synaptophysin, inhibin, vimentin and Melan-A. Negative results were obtained with cytokeratin and EMA. Thus, a cytodiagnosis of myxoid ACC was made.

Jain et al. [11] found in their study that no adenoma was larger than 5 cm and that no carcinoma was smaller than 6 cm Gross examination in our case revealed that the tumor had a diameter of 7.5 cm and that it weighed 543 g. The cut-section showed that the tumor had a variegated appearance with myxoid areas.

The Weiss system, first introduced in 1984, provides specific guidelines for differentiating adrenocortical adenoma from ACC, and is considered the standard for determining malignancy in tumors of the adrenal cortex. [12] The nine histological parameters evaluated in this system are high nuclear grade (nuclear grade III and IV based on the criteria of Fuhrman et al.), mitotic rate >5/50 high-power fields (HPF), atypical mitotic figures, clear tumor cell cytoplasm (less than 25% tumor cells), diffuse architecture (greater than 33% of tumor), necrosis, venous invasion, sinusoidal invasion and capsular invasion. [13] A tumor is labeled malignant when it meets four or more of these histological criteria.

Microscopic examination in our case showed a capsulated tumor composed of large cells with a high nucleocytoplasmic ratio, pleomorphic nuclei and prominent nucleoli. Myxoid areas were present. Diffuse architecture of the tumor was appreciated.

Clear cells were not found. A final diagnosis of myxoid ACC was made, in accordance with the Weiss criteria and the results of the relevant investigations that had been performed previously.

Misiæ et al. [14] stated in their study that a combined evaluation of clinical features, size or weight, microscopic appearance, immunohistochemical and molecular genetic data is necessary to ensure a correct diagnosis of adrenal masses.

To conclude, FNAC is a quick and reliable diagnostic method for ACC and immunocytochemistry plays a pivotal role in resolving diagnostic dilemma, especially to differentiate it from RCC.

 
   References Top

1.De Lellis RA, Mangray S. The adrenal gland. In: Mills SE, Carter D, Greenson JK, Reuter VE, Stoler MH, editors. Sternberg′s diagnostic surgical pathology. 5 th ed. Philadelphia: Lipincott Williams and Wilkins; 2010. p. 545-86.  Back to cited text no. 1
    
2.Fassina AS, Borsato S, Fedeli U. Fine needle aspiration cytology (FNAC) of adrenal masses. Cytopathology 2000;11:302-11.  Back to cited text no. 2
    
3.Fetsch PA, Powers CN, Zakowski MF, Abati A. Anti- alpha- inhibin: Marker of choice for the consistent distinction between adrenocortical carcinoma and renal cell carcinoma in fine needle aspiration. Cancer 1999;87:168-72.   Back to cited text no. 3
    
4.Dhawan SB, Aggarwal R, Mohan H, Bawa AS. Adrenocortical carcinoma: Diagnosis by fine needle aspiration cytology. Indian J Pathol Microbiol 2004;47:44-5.  Back to cited text no. 4
    
5.Lumachi F, Borsato S, Brandes AA, Boccagni P, Tregnaghi A, Angelini F, et al. Fine-needle aspiration cytology of adrenal masses in noncancer patients: clinicoradiologic and histologic correlations in functioning and nonfunctioning tumors. Cancer 2001;93:323-9.  Back to cited text no. 5
    
6.Wu HH, Cramer HM, Kho J, Elsheikh TM. Fine needle aspiration cytology of benign adrenal cortical nodules. A comparison of cytologic findings with those of primary and metastatic adrenal malignancies. Acta Cytol 1998;42:1352-8.  Back to cited text no. 6
    
7.DeWitt J, Alsatie M, LeBlanc J, McHenry L, Sherman S. Endoscopic ultrasound-guided fine-needle aspiration of left adrenal gland masses. Endoscopy 2007;39:65-71.  Back to cited text no. 7
    
8.Rosai J, Ackerman. Adrenal gland and other paraganglia. In: Rosai J, Ackerman, editors. Rosai and Ackerman′s surgical pathology. 10 th ed. New Delhi: Elsevier; 2011. p. 1057-100.  Back to cited text no. 8
    
9.Wick MR, Cherwitz DL, McGlennen RC, Dehner LP. Adrenocortical carcinoma: An immunohistochemical comparison with renal cell carcinoma. Am J Pathol 1986;122:343-52.  Back to cited text no. 9
[PUBMED]    
10.Miettinen M. Neuroendocrine differentiation in adrenocortical carcinoma: New immunohistochemical findings supported by electron microscopy. Lab Invest 1992;66:169-74.  Back to cited text no. 10
[PUBMED]    
11.Jain M, Kapoor S, Mishra A, Gupta S, Agarwal A. Weiss criteria in large adrenocortical tumors: A validation study. Indian J Pathol Microbiol 2010;53:222-6.  Back to cited text no. 11
[PUBMED]  Medknow Journal  
12.Weiss LM. Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 1984;8:163-9.  Back to cited text no. 12
[PUBMED]    
13.Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 1982;6:655-63.  Back to cited text no. 13
[PUBMED]    
14.Misiæ M, Vidas Z, Skegro D, Kocman B, Jeliæ-Puskariæ B, Kardum-Skelin I. Fine needle aspiration cytology of adrenocortical carcinoma-case report. Coll Antropol 2010;34:665-9.  Back to cited text no. 14
    

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Correspondence Address:
Santosh Kumar Mondal
"Teenkanya Complex", Flat 1B, Block B, 204 R N Guha Road, Dumdum, Kolkata - 700 028, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9371.138689

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