Myxoid Adrenal Cortical Carcinoma Presenting as Primary Hyperaldosteronism: Case Report and Review of the Literature
International Journal of Surgical Pathology 19(6) 803-807 C The Author(s) 2011 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/1066896909356925
SAGE
Min-Shu Hsieh, MD’, Jun-Herng Chen, MD’, and Long-Wei Lin, MD’
Abstract
The authors report a case of myxoid adrenal cortical carcinoma (ACC) clinically manifesting as primary hyperaldoste- ronism. The 82-year-old female patient had a history of hypertension and was sent to the emergency room because of change in consciousness. Ventricular fibrillation occurred, and severe hypokalemia was found. Increased renal loss of potassium, high serum aldosterone level, low renin activity, and a huge tumor in the left suprarenal area were revealed when tests were conducted to determine the cause of her hypokalemia. Left adrenalectomy was performed. The tumor measured 13 cm in diameter and showed a heterogeneous cut surface with gelatinous material. Microscopically, the lesion was composed of polygonal cells with eosinophilic cytoplasm and arranged in arborizing cords in a myxoid back- ground. Capsular and vascular invasion were observed. The tumor stained positive for synaptophysin, melan-A, vimentin, and a-inhibin but negative for cytokeratin. A primary myxoid ACC was diagnosed, which is a rare histological variant. The authors review 13 other reported cases. Most of these were functional tumors causing Cushing syndrome, and only 2 cases presented as primary hyperaldosteronism. All cases had similar microscopic and immunohistochemical features. Distal metastases and local recurrence were not uncommon. Close clinical follow-up is imperative.
Keywords
myxoid adrenal cortical neoplasm, primary hyperaldosteronism
Adrenal cortical carcinomas (ACCs) are rare malignancies with an incidence rate about 0.1 cases per million persons per year.1,2 They have a bimodal age distribution with a first peak in childhood and a second peak in the fourth and fifth decades.2 Clinically, most are functional tumors with clinical presentation as Cushing syndrome (in glucocorti- coid excess), virilization (in androgen excess), or hypoka- lemia (in mineralocorticoid excess). Cushing syndrome and virilization are common, whereas isolated hyperaldo- steronism is rare.3 Histologically, ACCs may show a wide range of differentiation, from tumors resembling corti- cal adenomas to frankly malignant, undifferentiated neo- plasms. Among them, the myxoid variant is very rare and was first reported in 1979.4 Currently, only 13 cases of myxoid ACCs are reported in the literature in English. Here, we report a case of myxoid ACC in an 82-year-old woman with primary hyperaldosteronism.
Report of the Case
This 82-year-old woman had a history of compression fracture and had undergone an operation. According to the
medical record, hypertension (blood pressure of 184/90 mm Hg in November 2008 and 220/119 mm Hg in June 2009) had been found in the past year. She was sent to our emer- gency room because of consciousness change. Laboratory examination showed severe hypokalemia (K: 1.9 mmol/L) and mild leukocytosis. Sudden collapse developed at the emergency room, and the electrocardiogram showed ven- tricular fibrillation. Return of spontaneous circulation was achieved after cardiopulmonary resuscitation and potas- sium chloride supplementation. Twenty-four-hour urine was collected, and the urine potassium level was 30.5 mmol/L. The daily potassium loss was 53.68 mmol/d despite hypokalemia. The transtubular potassium gradient was 7.62 (this should be less than 3 in a hypokalemic state), indicating renal loss of potassium. The arterial blood gas analysis also showed metabolic alkalosis (pH, 7.48;
“National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan
Corresponding Author:
Long-Wei Lin, Department of Pathology, No.579, Sec 2, Yunlin Rd, Douliou City, Yunlin County 640, Taiwan (ROC) Email: Y00679@ms1.ylh.gov.tw
pCO2, 38.7 mm Hg; HCO3 , 28 mmol/L). Increased serum aldosterone levels (315.3 ng/dL; normal, 5 to ~30 ng/dL) and decreased plasma renin activity (0.38 ng/mL/h; normal, 1.9-3.7 ng/mL/h) were found. The serum cortisol (23.6 ug/ dL; normal, 5 to ~24 µg/dL) and dehydroepiandrosterone sulfate (0.757 umol/L, normal 4.6 to ~15.4 umol/L) levels were not elevated. Primary hyperaldosteronism was con- sidered. A huge left adrenal tumor was later found by CT scan (Figure 1). Brain and chest CT scans showed no evi- dence of metastatic lesions. Left adrenalectomy was then performed.
The tumor submitted for pathological examination con- sisted of a solitary yellow tumor with a thin fibrous cap- sule and measuring 13 × 10 × 6 cm3 in size. Grossly, a heterogeneous cut surface showed gelatinous material and areas of necrosis and hemorrhage. The tumor weight was not recorded.
Microscopically, it showed an encapsulated, nodular lesion composed of polygonal cells with eosinophilic cyto- plasm and distinct cell borders. The nuclei were oval to round, with conspicuous nucleoli and coarse chromatin. The myxoid area accounted for 80% of the tumor and dis- played mixed architectural patterns, including arborizing cords (Figure 2A), trabeculae, pseudoglandular structures with intraluminal myxoid material, and small nests or sin- gle tumor cells floating in the myxoid background. A tran- sitional zone between mucin-poor and mucin-rich areas was seen. The remaining area resembled a conventional adrenal cortical neoplasm and was composed of trabecular organizations without myxoid background (15%), solid (3%), and clear cells (2%). Tumor necrosis, invasion of capsule (Figure 2B) or small vessels, and mitoses (average
A
B
C
D
4-5/50 HPF; Figure 2C) were observed. The clear cells showed clear cytoplasm filled with abundant intracyto- plasmic lipid droplets (Figure 2D). The residual adrenal gland was compressed to the periphery of the tumor.
The special stains showed that the myxoid area was dif- fusely positive for Alcian blue, mucicarmine, and periodic acid Schiff stains. No intracellular mucin was found. Ini- tially, a diagnosis of metastatic adenocarcinoma was favored because of its cord-like, pseudoglandular patterns, eosino- philic cytoplasm, and myxoid background. But all epithe- lial markers, including cytokeratin (AE1/AE3), CK7, CK20, and EMA (epithelial membrane antigen), were neg- ative. Primary adrenal cortical tumor was confirmed by diffusely and strongly positive stain for synaptophysin, melan-A, vimentin; focally positive stain for a-inhibin; and negative stain for S100, chromogranin-A, TTF-1, CDX-2, estrogen receptor, or PR. We evaluated the myx- oid and nonmyxoid components of this tumor according to the Weiss criteria5 proposed for diagnosing malignant adrenocortical neoplasms. The result is given in Table 1. The tumor presented a total Weiss score of 6 points, includ- ing high nuclear grade, ≤25% clear cells, necrosis, venous invasion, sinusoidal invasion, and capsular invasion. A myxoid ACC was diagnosed.
After the operation, her hypokalemia improved, and the patient was discharged with clinical follow-up. There is no evidence of local recurrence after 4 months.
| Trabecular Organizations With Myxoid Background | Trabecular Organizations Without Myxoid Background | Solid | Clear Cell | |
|---|---|---|---|---|
| Proportion of the tumor | 80% | 15% | ~3 | ~2% |
| Nuclear grade (Fuhrman) | III/IV | III/IV | III/IV | II-III/IV |
| Mitotic rate > 5/50 HPF | - (3/50 HPF) | - (4-5/50 HPF) | - (2/50 HPF) | - (<1/50 HPF) |
| Abnormal mitoses | − | − | − | − |
| ≤25% Clear cells | + | |||
| >1/3 Diffuse architecture | − | |||
| Necrosis | + | + | − | + |
| Venous invasion | − | + | − | − |
| Sinusoidal invasion | + | + | − | − |
| Capsular invasion | − | + | − | − |
| Total Weiss score | 6 |
Comment
Myxoid change is a rare histological pattern in adrenal cortical neoplasms and is found in both benign and malig- nant lesions. To the best of our knowledge, there are only 14 cases (including the present one) of myxoid ACCs reported in the literature in English.4,6-10 The clinical and pathological features are listed in Table 2. The age range is from 38 to 82 years (average 51.2), and the gender ratio was equal (male:female, 7:7). Clinically, most cases (12/14) presented with adrenocortical endocrinopathy, including Cushing syndrome (8/14), primary hyperaldosteronism (2/14), or markedly elevated serum cortisol levels (2/14). The size and weight of the tumor ranged from 6 to 17.5 cm (mean, 9.5; average, 10.6 cm) and 65 to 900 g (mean, 194; average, 337 g). The proportion of myxoid area varied in these cases (from 10% to 80% of the total area). The myx- oid portion stained positive for Alcian blue in all cases (except one in which Alcian blue stain was not performed). A minority (4/14) was also positive for mucicarmine or peri- odic acid Schiff stains. This staining pattern favored acid mucopolysaccharides, consistent with connective tissue- type mucin (Figure 3).11
Morphologically, all lesions were composed of polygo- nal cells with eosinophilic cytoplasm. The most common architecture was anastomosing cords or trabeculae, fol- lowed by solid and pseudoglandular patterns. The non- myxoid area in each reported case was similar to that for conventional adrenal cortical neoplasms. Most cases had frankly malignant features, including necrosis (9/13), vascular and/or capsular invasion (12/14), and increased mitotic figures (>5/50 HPF; 10/14). In the previously reported 13 cases, we do not know whether these malig- nant features were present in myxoid areas or in areas of conventional ACC. In our case, the nonmyxoid portion had a Weiss score of 6, whereas the myxoid area had a score of 3. Even though both components fulfill the Weiss criteria
for malignancy, the nonmyxoid, conventional ACC area may have a greater effect on the clinical prognosis in this case.
Because of the unusual myxoid background, arborizing trabecular pattern, and absence or minimal amount of clear cells, it is difficult to differentiate myxoid ACC from a met- astatic adenocarcinoma without the aid of immunohisto- chemical stains. The immunohistochemical staining results of the reported myxoid ACCs are listed in the Table 3. Syn- aptophysin, melan-A, a-inhibin, and vimentin are the most commonly expressed proteins. Cytokeratin was only posi- tive in 1 case. This is a very useful panel for discriminating primary adrenocortical carcinomas from metastatic adeno- carcinomas. In addition, because of its retroperitoneal loca- tion and usual absence of cytokeratin expression, the differential diagnosis should also include sarcomas with myxoid substances, such as extraskeletal myxoid chondro- sarcoma, liposarcoma, chordoma, parachordoma, or nerve sheath tumors.6,9,11 Clinical information such as adrenal endocrinopathy or suprarenal location is also important.
The prognosis for myxoid ACC is poor-most cases (11/14) developed distant metastasis during clinical follow- up. Liver is the most commonly involved organ (6/11), followed by lung or pleura (3/11), omentum (1/11), brain (1/11), and eye (1/11). Local recurrence is not uncom- mon (4/14).
In summary, we have reported a rare case of adrenal tumor with clinical presentation as primary hyperaldoste- ronism. Morphologically, the tumor cells formed anasto- mosing trabecular or cord patterns separated by mucinous materials. It resembled a metastatic carcinoma with extra- cellular mucin secretion and was distinct from conventional adrenal cortical neoplasms, which often have abundant and delicate sinusoidal structures. A primary myxoid ACC was confirmed by a panel of immunostains, including pos- itive stains for synaptophysin, melan-A, vimentin, and a-inhibin, and negative stains for cytokeratin or other
| Case | Age/Sex | Size (cm)/ Weight (g) | Adrenal Endocrinopathy | Mitoses | Necrosis | Vessel/Capsular invasion | Myxoid Area | Metastasis | |
|---|---|---|---|---|---|---|---|---|---|
| Percentage | Special Stainsª | ||||||||
| 14 | 41/F | 9/NA | − | 0 | − | -/- | NA | Alcian blue (+) | +, Pleura |
| 26 | 45/M | 17.5/900 | Cushing syndrome | 2/50 HPF | + | +/- | 10 | Alcian blue (+), mucicarmine (weak +) | + |
| 37 | 44/F | 9/180 | Markedly elevated cortisol level | 4/10 HPF | − | -/- | 60 | Alcian blue (+) | − |
| 47 | 48/M | 7.7/151.9 | Primary hyperaldosteronism | 7/10 HPF | + | -/+ | 20 | Alcian blue (+) | +, Liver, and local recurrence |
| 57 | 43/F | 8/65 | Cushing syndrome | 6/10 HPF | − | -/+ | 10 | Alcian blue (+) | +, Omentum, and local recurrence |
| 67 | 48/M | 9/195 | Cushing syndrome | 5/10 HPF | − | +/+ | 50 | Alcian blue (+) | +, Liver |
| 77 | 53/F | 8.4/138 | Cushing syndrome | 13/10 HPF | + | -/+ | 60 | Alcian blue (+) | +, Liver, eye, lung |
| 87 | 51/M | 16/700 | Cushing syndrome | 5/10 HPF | + | +/+ | 60 | Alcian blue (+) | +, Brain |
| 97 | 63/F | 11/NA | Cushing syndrome | 9/10 HPF | + | 20 | Alcian blue (+) | +, Liver | |
| 107 | 56/F | 10/470 | Cushing syndrome | 3/10 HPF | + | +/- | 30 | Alcian blue (+) | +, Lung |
| + elevated aldosterone level | |||||||||
| 118 | 38/M | 13.5/380 | Markedly elevated | Positive | NA | +/+ | NA | Alcian blue (+) | +, Bone, liver, and |
| cortisol and | but not | local recurrence | |||||||
| aldosterone levels | counted | ||||||||
| 129 | 49/M | 6/NA | − | 4-5/HPF | + | +/NA | NA | Mucicarmine (weak +), PAS (weak +) | − |
| 1310 | 61/M | 10/192.8 | Cushing syndrome | >25/50 HPF | + | +/+ | NA | Alcian blue (+) | +, Liver, lung, and local recurrence |
| Present | 82/F | 13/NA | Primary hyperaldosteronism | 4-5/50 HPF | + | +/+ | 80 | Alcian blue (+), | − |
| mucicarmine | |||||||||
| (weak +), PAS (weak +) | |||||||||
Abbreviations: NA, not available; PAS, periodic acid Schiff.
ªOne of the 8 cases (case 3-1 1) was positive for mucicarmine and PAS stains.
A
B
| Synaptophysin | Melan-A | a-Inhibin | Vimentin | Cytokeratin | |
|---|---|---|---|---|---|
| Positive | 12/12 | 12/12 | 12/12 | 10/11 | 1/12 |
| cases/ cases with available IHC stain results |
Abbreviation: IHC, immunohistochemical.
epithelial markers, and a total Weiss score of 6. Because of the high risk of distant metastasis and local recurrence, close clinical follow-up is mandatory.
Declaration of Conflicting Interests
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
Funding
The authors received no financial support for the research and/or authorship of this article.
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