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BRIEF REPORT
Fine needle aspiration cytology of a myxoid adrenocortical adenoma. A case report
Alwalid Freih-Fraih MD1 | Carlos H. Gordillo MD1
Alberto Mingo MD2
Rosario Serrano-Pardo MD1 |
Jose A. Jimenez-Heffernan MD1
1Department of Pathology, University Hospital La Princesa, Madrid, Spain
2Department of Radiology, University Hospital La Princesa, Madrid, Spain
Correspondence
José A. Jiménez-Heffernan MD, Departamento de Anatomía Patológica, Hospital Universitario La Princesa, Diego de León, 62, Madrid-28006, Spain. Email: joseantonio.jimenez@uam.es
Abstract
The myxoid variant of adrenocortical (AC) tumors is characterized by peculiar histologic features that differ from conventional ones. It shows a prominent myxoid stromal component and is composed of small cells with mild atypia arranged in cords, pseudoglandular structures and microcysts. Reflecting the rarity of this variant, very few cytologic descriptions are available. We describe one case in a 41-year-old woman with a previous diagnosis of breast carcinoma and BRCA1 mutation. During follow-up controls, an adrenal tumor was discovered. Fine needle aspiration cytology and Tru-Cut biopsies were performed simultaneously. Smears showed numerous groups of cohesive cells of intermediate to small size. Within the largest groups, aggregates of myxoid metachromatic material were evident. This myxoid material could also be observed as isolated acellular fragments. While the cytoplasm of most tumoral cells was homogenously stained some showed small vacuoles. Histologically, the tumor grew, forming anastomosing cords, separated by myxoid material that determined microcystic spaces. Immunohistochemistry was characteristic of AC myxoid tumor. After surgery, pathologic analysis confirmed this diagnosis. The tumor showed no necrosis or invasion, had a low mitotic index (3/50 high power fields) and Ki-67 proliferative index of 15%. According to the different diagnostic systems the tumor was classified as an adenoma. In conclusion, the myxoid variant of AC tumors shows peculiar cytologic features. If unaware of the existence of this variant, it can easily be misinterpreted as a metastatic tumor.
KEYWORDS
adrenal gland, adrenocortical tumor, cytology, fine needle aspiration
1 INTRODUCTION
In 2005 Tang et al., described a variant of adrenocortical (AC) carcinoma characterized by a relevant myxoid stroma and pecu- liar cyto-architectural morphology.1 This variant of AC tumors, which now, includes adenomas and carcinomas, is uncommon and has been reported as single cases or small series.2-4 Focal myxoid changes can be seen in conventional AC carcinoma with large, atypical eosinophilic cells and solid growth. However, the so called myxoid variant of AC
carcinoma refers to tumors with a prominent myxoid stromal compo- nent composed of small cells with mild atypia arranged in cords, pseudoglandular structures and microcysts.2-4 Indeed, its histopatho- logic appearance is so unusual that it may be difficult to recognize it as an AC tumor. Fortunately, they express the same immunohisto- chemical markers as conventional ones allowing a precise diagnosis. The tumor expresses Melan-A, «-inhibin, calretinin, steroidogenic fac- tor 1 and synaptophysin and is negative for cytokeratins AE1/AE3 and chromogranin.4 As expected, due to its rarity, cytologic cases are
limited to two case reports.5,6 In this report we describe cytologic fea- tures of another case of myxoid AC adenoma and discuss the possibil- ity of a precise recognition and potential diagnostic pitfalls.
2 CASE REPORT |
The patient is a 41-year-old woman who underwent surgery 6 years ago due to an infiltrating ductal breast carcinoma. She was subse- quently found to harbor a mutation in the BRCA1 gene. During follow-up controls, a 35 mm right adrenal tumor was incidentally dis- covered. The patient had no pheochromocytoma related symptoms and biochemical analyses were normal. More precisely, the patient suffered no hypertension, headaches, palpitations or tachycardia epi- sodes. Urinary tests for vanillylmandelic acid, catecholamines and metanephrines, and plasma tests for catecholamines and chomogranin A were normal. Computed tomography study favored a primary adre- nal lesion but could not exclude metastasis. Ultrasonographic-guided fine needle aspiration (FNA) cytology and Tru-Cut biopsy of the adre- nal lesion were performed simultaneously. Cytologic smears were air- dried and stained with Diff-Quik. Since tissue material was available, no liquid cytology was obtained. Smears showed a double cellular component that correlated with observed in Tru-Cut biopsies. The most abundant cell population consisted of groups of cohesive cells of intermediate to small size. Within the largest groups aggregates of myxoid metachromatic material were evident (Figure 1(A)-(C)). This myxoid material could also be observed as isolated acellular frag- ments. Tumor cells had a polygonal morphology with well-defined cel- lular limits, and round uniform nuclei with no relevant pleomorphism.
While the cytoplasm of most tumoral cells was homogenously stained some showed small vacuoles (Figure 1(C)-(E)). No clear cell compo- nent was present. Tru-Cut histologic samples showed normal cortical tissue in continuity with the tumoral component without a capsule in between. The tumor formed anastomosing cords that determined microcystic spaces (Figure 2(A)). Cords were separated by abundant myxoid substance that was also present within the microcysts. Tumor cells resembled those seen on cytology. They were small, cuboidal with scarce basophilic cytoplasm and round nuclei without relevant atypia (Figure 2(B). As expected, a reticulin stain showed loss of the normal reticulin network. Mitotic activity was lower than 5/50 high power fields, and no atypical mitoses were seen. Immunohistochem- istry revealed no expression of GATA3, estrogen receptor, AE1/AE3 cytokeratins (Figure 2(C)) and WT1. On the contrary, it was positive for vimentin, calretinin, Melan A (Figure 2(D)) and synaptophysin. The proliferative index with Ki-67 was 15%. The pathologic diagno- sis was of a myxoid AC tumor. Admitting the difficulties of esta- blishing a diagnosis of malignancy in Tru-Cut samples, the present case showed worrisome features such as direct continuity with adrenal gland (lack of capsule), loss of reticulin network, and high Ki67 index.4 A pathologic diagnosis of AC tumor, myxoid variant was made mentioning that it could correspond to a carcinoma. The patient was lost to follow up, but 1 year later she returned to the Hospital and underwent surgery. Pathologic analysis revealed a 4 cm adrenal tumor with the same myxoid morphology and immuno- histochemistry profile as seen in the Tru-Cut biopsy. The tumor showed no necrosis or invasion and had a low mitotic index (3/50 high power fields). A similar Ki-67 proliferative index (15%) was observed. According to the different diagnostic systems (Weiss,
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3 DISCUSSION
In this report, we have presented cytologic features of a myxoid variant of AC adenoma. Its morphology differs considerably from conventional primary adrenal tumors and must be considered to avoid misdiagnosing it as metastatic carcinoma. Conventional AC adenomas and carcinomas show large, polygonal cells with vari- able atypia. They possess abundant cytoplasm that often is micro- vacuolized or has oncocytic features. Cytoplasmic fragility often results in a lipid-rich background which is a very helpful diagnostic feature better visualized with Diff-Quik or related stains.7 Simi- larly, other primary adrenal tumors such as pheochromocytoma or myelolipoma differ considerably from the myxoid variant we have presented.8 Therefore, the most important differential diagnosis of the myxoid variant of AC tumors are metastatic carcinomas, especially mucinous ones. In a large study of 464 patients with adrenal metastases, origins from lung, stomach, esophagus, liver/ bile duct, pancreas, large intestine, kidney and breast were the most common primaries.9 Many of these carcinomas can have either evident mucinous production or focal mucinous component creating an extensive differential diagnosis. Our patient had an antecedent of breast carcinoma. Mucinous production in infiltrat- ing carcinomas is usually seen in the ductal type.1º However, it has also been reported in lobular carcinoma.11 When evaluating cytologic smears and histologic sections we considered the morphology to differ from the patient’s prior infiltrating ductal
breast carcinoma. Immunohistochemistry were also useful for differentiation.
We are aware of two cytologic reports of myxoid AC tumors.5,6 In one case they describe large cells in a myxoid background that raised a differential diagnosis with renal cell carcinoma.6 The second case is based exclusively on Papanicolaou stained smears so compari- son with our case is difficult.5 Even with Papanicolaou stain the authors were able to identify mucin and stained it with Alcian blue. They describe and illustrate large tumoral cells with centrally located small round nuclei with an occasional single nucleolus.5 In the report by Papotti et al., the FNA morphology is described as a diffuse growth of small-medium size cells with hyperchromatic nuclei and no myxoid background.3 In their report the staining method is not described. In our case, Diff-Quik allowed a precise evaluation of the cytoplasm and small vacuoles resembling those of normal cortical cells were present in several tumoral cells. In retrospect, we believe that they are an important clue for the specific recognition of this entity.
Another interesting aspect of this patient is that she had a muta- tion in the BRCA1 gene. In addition to breast and ovarian cancers, mutations in BRCA1 have been described in numerous tumors although only melanoma has an established association.12 In the case of BRCA2 mutations there is also an increased risk for pancreatic and prostatic carcinoma.12 A recent case of AC carcinoma related to BRCA2 mutation has been reported.13 Recent studies concerning molecular pathways involved in AC carcinoma development do not include abnormalities in BRCA genes.4,14,15 In conclusion, the myxoid variant of AC tumors shows peculiar cytologic features that should alert the pathologist to perform immunohistochemical studies. If unaware of the existence of this variant it can easily be misinterpreted as a metastatic tumor.
AUTHOR CONTRIBUTIONS
Patient diagnosis: Alwalid Freih-Fraih, Rosario Serrano-Pardo, Alberto Mingo, José A. Jiménez-Heffernan; Literature review: Carlos H Gordillo, Alberto Mingo, José A. Jiménez-Heffernan; Manuscript prep- aration: José A. Jiménez-Heffernan, Carlos Gordillo.
DATA AVAILABILITY STATEMENT
Data sharing not applicable to this article as no datasets were gener- ated or analysed during the current study.
ORCID
José A. Jiménez-Heffernan (D https://orcid.org/0000-0002-2113-2972
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How to cite this article: Freih-Fraih A, Gordillo CH, Mingo A, Serrano-Pardo R, Jiménez-Heffernan JA. Fine needle aspiration cytology of a myxoid adrenocortical adenoma. A case report. Diagnostic Cytopathology. 2021;49(9):E360-E363. https://doi.org/10.1002/dc.24811