ELSEVIER
Case study
A case report of adrenocortical carcinosarcoma with oncocytic and primitive neuroectodermal-like features
Chia-Sui Kao MD*, David J. Grignon MD, Thomas M. Ulbright MD, Muhammad T. Idrees MD
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA Received 14 December 2012; accepted 14 January 2013
Keywords:
Adrenocortical; Primitive neuroectodermal tumor;
PNET; Carcinosarcoma; Sarcomatoid carcinoma; Morphology; Immunohistochemistry
Summary Adrenocortical carcinosarcomas are rare aggressive neoplasms; only a few have been reported to date, all with dismal prognosis. These were reported as having varying morphology. We have encountered a case of adrenal carcinosarcoma with an undifferentiated component bearing similarities to primitive neuroectodermal tumors and other areas of oncocytic differentiation. The 48-year-old woman patient presented with abdominal pain and unintended, excessive weight loss. Computed tomographic imaging revealed a tumor located adjacent to the liver and kidney necessitating a partial nephrectomy and hepatectomy. Histologically, the tumor exhibited malignant features. Melan-A, inhibin, calretinin, cytokeratin AE1/AE3, synaptophysin, and neuron-specific enolase were positive immunohistochemi- cally. The patient developed metastasis within 2 months of surgery and is currently alive with disease after chemotherapy. Adrenal carcinosarcoma is a rare highly aggressive malignancy with a wide morphologic spectrum. Recognition of variant morphology and applying correct immunohistochemical studies will aid in reaching an accurate diagnosis.
@ 2013 Elsevier Inc. All rights reserved.
1. Introduction
Carcinosarcomas are malignant neoplasms showing both epithelial and mesenchymal differentiation. Those occurring in the adrenal gland are extremely rare and aggressive. The term sarcomatoid carcinoma has also been used synony- mously to refer to this particular type of neoplasm. Adrenocortical carcinoma has an estimated annual incidence of 1.5 to 2 per million population and predominantly affects women [1]. The age of occurrence has a bimodal distribution with 2 peaks: one in childhood before age 5 years and the other in the fourth to fifth decades. The prognosis is poor with a significant proportion (21%-39%) of patients having distant metastasis at the time of presentation and a 5-year
overall survival range of 38% to 60% [1]. Even after a surgical resection (adrenalectomy) with apparent clear margins, most patients develop early tumor recurrence or distant metastasis [1]. The few documented examples of adrenal carcinosarcoma have demonstrated a similar highly aggressive clinical behavior.
The first case of adrenocortical carcinosarcoma was reported in 1987 by Okazumi et al [2]. Since then, 10 additional cases have been reported in the literature [2-12]. Adrenocortical carcinosarcomas exhibit a wide spectrum of morphologic findings, ranging from a typical adrenal carcinoma with a component of undifferentiated spindle cell proliferation [2,3,7-9] to heterologous features including rhabdomyoblastic [4,5,10,11], chondroid, and osteogenic differentiation [4,6].
We present a case of adrenocortical carcinosarcoma with unusual and interesting morphology: an undifferentiated
* Corresponding author.
E-mail address: yutkao@iupui.edu (C. - S. Kao).
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component mimicking primitive neuroectodermal tumor (PNET) not previously reported in the literature. We herein report this case to expand the morphologic and clinicopath- ologic features and provide a pertinent literature review.
2. Case presentation
A 48-year-old woman with a history of type II diabetes mellitus and hypertension presented with a 12-month history of right upper quadrant abdominal pain, hypokalemia, and a 60-lb weight loss. Computed tomography of the abdomen and pelvis showed a heterogeneously enhancing right adrenal mass measuring 12 × 11 cm, displacing the right kidney; no other lesions or lymphadenopathy was identified. At the time of surgical resection (adrenalectomy), the mass was found to infiltrate into the kidney and was adherent to the liver, necessitating a partial nephrectomy and partial hepatectomy.
2.1. Gross pathology
The gross specimen consisted of a 14.9 x 13.3 × 9.0 cm lobulated, irregular mass with attached 5.7 x 4.5 x 1.5 cm partial nephrectomy specimen and a 5.2 × 1.9 × 0.5 cm portion of liver with a moderate amount of adherent fat. The
total specimen weighted 760 g and measured 14.9 cm. Sectioning displayed a well-delineated, lobulated, hetero- geneous, tan-pink to red, focally hemorrhagic, and necrotic (5%) mass. No definitive extension into the kidney or liver parenchyma was identified on gross examination. A compressed normal-appearing adrenal gland was identified at the periphery of the tumor, measuring 1.3 x 1.2 x 0.5 cm (Fig. 1A). No lymph nodes were present in the attached fat.
2.2. Microscopic findings
The tumor consisted of both epithelial and spindle cells with 3 distinct patterns. Approximately 40% was composed of large, epithelioid, and polygonal cells with eccentric nuclei, usually with prominent nucleoli, and abundant granular, intensely eosinophilic cytoplasm (Fig. 1B). Al- though most areas showed sheets of polygonal cells without prominent stroma, there were some hypocellular fields that showed anastomosing cords of epithelial cells within abundant myxoid background (Fig. 1C). Approximately 35% of the tumor was a spindle cell proliferation growing in solid sheets with a vague storiform pattern. The pleomorphic spindle cells had hyperchromatic nuclei with dispersed chromatin. Most spindle cell areas showed interspersed abrupt transitions between spindle cells and solid sheets or small islands of epithelioid polygonal cells (Fig. 1D). The third pattern, consisting of 25% of the tumor, was an
| Table 1 Antibodies used for immunohistochemistry and staining results | |||||
|---|---|---|---|---|---|
| Antibody | Source | Dilution | Carcinoma | Spindle cell | Undifferentiated |
| AE1/AE3 | Zymed Laboratories ª | 1:50 | ++, focal | -ve | -ve |
| Calretinin | Invitrogenb | 1:100 | ++, focal | ++, focal | ++, focal |
| Chromogranin | Dakoc | 1:300 | -ve | -ve | -ve |
| CD117 (c-kit) | Dako | 1:200 | -ve | -ve | +, focal |
| CD99/HBA.71 | Dako | RTU | -ve | nonspecific | ++ (membranous), focal |
| Desmin | Dako | 1:50 | -ve | -ve | -ve |
| FLI-1 | Santa Cruz Biotechnology | 1:80 | ++ | ++ | ++ |
| GFAP | Dako | RTU | -ve | -ve | -ve |
| HMB45 | Dako | 1:100 | +, focal | +, focal | +, focal |
| Inhibin | Novocastra Laboratories e | 1:50 | +, focal | +, focal | +, focal |
| Melan-A | Dako | 1:25 | +++ | ++, focal | ++, focal |
| Myogenin | Dako | 1:100 | -ve | -ve | -ve |
| Myoglobin | Signetf | RTU | -ve | -ve | -ve |
| NSE | Dako | RTU | + | -ve | -ve |
| OCT4 | Cell Marque & | RTU | -ve | -ve | -ve |
| S-100 protein | Dako | 1:1500 | -ve | -ve | -ve |
| Synaptophysin | Dako | 1:100 | +, focal | -ve | -ve |
| Vimentin | Dako | 1:25 | +++ | +++ | +++ |
Abbreviation: RTU, ready to use.
a Calsbad, CA.
b Camarillo, CA.
c Carpinteria, CA.
d Dallas, TX.
e New Castle, UK.
f Dedham, MA.
g Rocklin, CA.
A
B
C
D
undifferentiated, round blue cell pattern, with perivascular clustering and vague pseudorosettes, resembling a PNET (Figs. 1E and 1F). Most of the tumor necrosis was associated with this type of morphology. No specific mesenchymal differentiations (ie, rhabdomyoblastic, osteogenic, or chon- dromatoid) were identified on the hematoxylin and eosin- stained sections. Only rare (<5%) clear cell areas were present. An estimated 20% of the tumor was necrotic on microscopic examination. Variable numbers of mitoses were identified in different areas. The highest mitotic activity was observed in sarcomatous and undifferentiated areas, whereas only occasional mitoses were observed in the epithelioid component. The average mitotic activity was 10 per 10 high-power fields (HPFs) (range, 5-30/10 HPF). An intact portion of uninvolved adrenal gland was identified, compressed and adherent to the periphery of the tumor. Vascular invasion within a large caliber vessel was identified in this area of tumor adjacent to the identifiable adrenal gland. The tumor was adherent to the liver and renal capsules; however, no direct invasion into the liver or renal parenchyma was identified.
2.3. Immunohistochemical findings
A comprehensive panel of immunohistochemical stains was performed (Table 1) on formalin-fixed, paraffin- embedded tumor tissue using a polymer-based method (EnVision FLEX or FLEX+; Dako, Carpinteria, CA) and diaminobenzidine as the chromogen in a Dako automated immunostaining instrument. Negative and positive controls were performed for each immunohistochemical stain. Melan- A showed strong diffuse positivity, predominantly in the oncocytic epithelial cells with focal positivity in the sarcomatous areas (Fig. 2A). Inhibin and calretinin were weakly and focally (5%) positive. Cytokeratin AE1/AE3 and synaptophysin (Fig. 2B) were focally positive in only the oncocytic epithelial cells. CD117 (c-kit) showed focal, weak positivity in the undifferentiated areas. CD99 showed focal moderate membranous staining in the undifferentiated areas (Fig. 2C) and diffuse nonspecific cytoplasmic staining in the sarcomatous areas. FLI-1 showed positive nuclear reactivity in all 3 components (Fig. 2D). Neuron-specific enolase (NSE) was positive in only the oncocytic epithelioid areas.
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Vimentin was diffusely and strongly positive in all 3 components. GFAP, chromogranin, HMB-45, OCT4, myo- globin, desmin, S-100, and myogenin showed no reactivity.
2.4. Electron microscopic/ultrastructural findings
Ultrastructural studies were performed on formalin- fixed, paraffin-embedded sections of tumor and examined with an FEI Tecnai Bio Twin transmission electron microscope operated at 80 kV. Images were captured with an AMT XR 60 digital camera. The epithelial component of the tumor consisted of round to ovoid cells, with some nuclei containing a solitary nucleolus; junctional complexes, abundant mitochondria along with a few neurosecretory-like granules, and lipid bodies were observed within the cytoplasm. Cells of the spindle cell component displayed a large nuclear-to-cytoplasmic ratio with occasional bundles of intermediate filaments and the same cell organelles observed in the epithelial component. The poorly differentiated cells displayed large oval nuclei
and numerous lipid droplets, with occasional neurosecre- tory granules (Fig. 3).
2.5. Clinical follow-up
The patient developed metastasis involving the lungs and liver 2 months after surgical resection. Metastatic tumor nodules showed moderate shrinkage after 3 rounds of chemotherapy including cisplatin and ifosfamide. The patient is currently alive with disease 7 months after surgery and is being followed up closely for recurrent and metastatic disease.
3. Discussion
Adrenocortical carcinosarcomas are rare and aggressive neoplasms, with less than a dozen reported in the English language literature to date. The first case of adrenocortical carcinosarcoma was reported by Okazumi et al [2], yet the detailed pathologic features were described by Collina et al in
| Reference | Age/ sex | Clinical presentation | Laboratory data | Stage/extent ª | Treatment b | Tumor size, weight | Morphology ℃ | Positive immunostains | Clinical follow-up |
|---|---|---|---|---|---|---|---|---|---|
| Okazumi et al | 46/ | Abdominal | Normal | Extending into | Adrenalectomy | 14 cm, | Spindle cells | Not available | 5 mo: recurrence |
| [2], 1987 | M | distention, back pain | right atrium via right adrenal vein | Nephrectomy | 880 g | 206th day: death | |||
| Collina et al | 68/F | Abdominal | Normal | Replacing right | Adrenalectomy | 11 cm | Spindle cells | Low molecular | 2 mo: soft tissues, |
| [3], 1989 | discomfort | adrenal gland | RT | Occasional | weight CK | vertebral metastases | |||
| CT: C, E | giant cells | Vimentin | 3 mo: lung, liver, abdomen metastases 6 mo: death | ||||||
| Decorato et al | 42/F | Abdominal | Normal | Left upper quadrant | Tumor excision | 19 cm, | Epithelial | Sarcomatous: | 3 mo: pleural |
| [4], 1990 | and flank pain | retroperitoneal mass | 1400 g | Spindle cells | muscle specific | metastases | |||
| Rhabdomyosarcoma | actin | 7 mo: death | |||||||
| Fischler et al | 29/F | Amenorrhea, | 1 Androstenedione | Suprarenal mass | Adrenalectomy | 12.5 cm, | Epithelial | Vimentin in all | 4 mo: retroperitoneal |
| [5], 1992 | fatigue, weight | ¡DHEA-SO4 | with renal | Nephrectomy | 610 g | Spindle cells | components | recurrence with | |
| loss, 1body musculature, clitoromegaly, hirsutism | ¡Total T | vein thrombosis | Splenectomy | Rhabdomyosarcoma | Rhabdomyosarcoma: HHF and desmin | lymphadenopathy, | |||
| 1Free T îplasma cortisol | AT: M CT: C, E | liver, and vertebral | |||||||
| metastases | |||||||||
| 8 mo: death | |||||||||
| Barksdale | 79/F | Severe | Hypokalemia | Calcified mass | Adrenalectomy | 9 cm, | Epithelial polygonal | Vimentin in all | 4 mo: vertebral |
| et al [6], 1993 | hypertension | 1 Aldosterone | close to inferior vena cava | Cavotomy | 199 g | Osteosarcoma Chondrosarcoma | components | and liver metastases | |
| Lee et al | 61/ | Flank and | 124h | Upper pole of | Adrenalectomy | 12 cm | Epithelial | CK in both | Second day: death |
| [7], 1997 | M | back pain | urine | kidney with capsular | Nephrectomy | polygonal | components | ||
| VMA | involvement and invasion of right | Hepatic lobectomy | Spindle cells | Epithelial: focal NSE | |||||
| lobe of liver | Sarcomatous: vimentin | ||||||||
| Sturm et al | 31/ | Asthenia, | Normal | Left adrenal mass | Adrenalectomy | 12 cm, | Epithelial clear cells | CD56, vimentin, | 2 mo: recurrence |
| [8], 2008 | M | abdominal | impinging on | CT: C | 620 g | Spindle cells | focal desmin in | involving spleen | |
| pain | pancreas and spleen | "Few" giant cells | both components | 3 mo: death | |||||
| Epithelial: CK | |||||||||
| AE1/AE3, a-inhibin, synaptophysin Sarcomatous: HHF35 | |||||||||
| Coli et al | 75/F | Abdominal | Normal | Left adrenal mass | Adrenalectomy | 15 cm | Epithelial | Epithelial: CK | 3 mo: liver |
| [9], 2010 | pain | displacing the | Regional | Spindle cells | (MNF-16), vimentin, | metastases | |||
| pancreatic tail | lymphadenectomy | Giant cells | S-100, Melan-A, | 12 mo: death | |||||
| and spleen | Splenectomy | focal HMB45 | |||||||
| Sarcomatous: vimentin, | |||||||||
| SMA, desmin, caldesmon, myogenin |
| Sasaki et al | 45/ | Abdominal | Normal | Left retroperitoneal | Nephrectomy Colectomy | 17 cm, 2974 g | Epithelial polygonal Spindle cells | Vimentin, | 3 mo: death |
|---|---|---|---|---|---|---|---|---|---|
| [10], 2010 | M | pain, fever, | mass | synaptophysin, melan-A, and | |||||
| nausea, | Bilobar liver | Splenectomy | Rhabdomyosarcoma | ||||||
| vomiting, Įappetite, weight loss | metastasis | Distal pancreatectomy Liver biopsy | calretinin in both components Rhabdomyosarcoma; desmin, myogenin, myoglobin | ||||||
| Bertolini | 23/F | Fatigue, | Normal | Left adrenal and | Laparoscopic | 14 cm | Epithelial | Epithelial: inhibin, | 13 mo: brain |
| et al | Įappetite, | a rectal mass | adrenalectomy | Osteosarcomatous | calretinin | metastasis | |||
| [12], 2011 | fixed mass in | Pulmonary, rectal, | Iliac colostomy | 14 mo: death | |||||
| rectum on | hepatic, nodal and | CT | |||||||
| pregnancy examination | sacral metastasis | RT | |||||||
| Thway et al | 45/ | Bloating, | Normal | Left retroperitoneal | Adrenalectomy | 24 cm, | Epithelial | Epithelial: melan-A, | 8 mo: brain |
| [11], 2012 | M | back pain | mass, nodal and | Splenectomy Nephrectomy Lymphadenectomy CT: V, I, D, E | 6500 g | Rhabdomyosarcoma | CD56, MNF116 Sarcomatous: desmin, myogenin | metastasis 11 mo: death | |
| lung metastasis | |||||||||
| Kao et al, | 48/F | Abdominal | Hypokalemia | Right adrenal | Adrenalectomy | 15 cm, | Epithelial | Epithelial: melan-A, | 2 mo: lung and |
| 2012 | pain, weight loss | mass adherent to kidney and liver | Partial hepatectomy Partial nephrectomy CT: I, C | 760 g | spindle cells Undifferentiated | inhibin, calretinin, AE1/3, synaptophysin All components: vimentin, NSE, FLI-1 Undifferentiated: CD99 (membranous) | liver metastasis 7 mo: alive | ||
| after 3 rounds of CT |
Abbreviations: CK, cytokeratin; T, testosterone; AT, adjuvant therapy; CT, chemotherapy; RT, radiation therapy; SMA, smooth muscle actin; C, cisplatin; E, etoposide; M, mitotane; I, ifosfamide; V, vincristine; D, doxorubicin.
a Metastasis, organs of invasion at presentation.
b Surgical, chemo/radiation.
” Epithelial, spindle or heterologous.
d Postsurgical outcome.
1989 [3]. Only 10 additional cases have been reported in the literature since then [2-11]. The present case of adrenal tumor was extensively sampled and showed both carcinomatous as well as sarcomatous components; however, heterologous elements as described in some previous publications were not observed. Rather, the most striking feature was the widely variable morphologic patterns. In addition to typical cortical carcinoma and pleomorphic spindle cell sarcoma, there was a third poorly differentiated, round blue cell component, bearing a striking resemblance to PNET. This third component showed areas of whorling perivascular clustering as well as vague pseudorosettes. Most of the tumor necrosis and brisk mitotic activity was associated with this undifferentiated tumor component. These morphologic findings together with positive immunoreactivity for CD99 and FLI-1 raised the possibility of a coexisting PNET. Although the immunohis- tochemical staining results were not specific, the electron microscopy findings suggested PNET differentiation.
Within the carcinomatous component, there were areas of round “epithelioid” cells with abundant eosinophilic cyto- plasm and eccentrically located round-to-oval nucleus, similar to the cells seen in oncocytic adrenal neoplasms. These were the only tumor cells that showed positive reactivity with cytokeratin AE1/AE3, synaptophysin, and NSE. A previous study documented neuroendocrine differentiation in adreno- cortical carcinomas, as evidenced by positive staining for NSE, synaptophysin, and neurofilament protein [13], and our immunohistochemical staining results are similar.
Another interesting aspect of this case was that the mass was adherent to a portion of encapsulated, normal-appearing adrenal gland without clear transition of benign to malignant foci. It is probable that the tumor arose from a nodular area of the adrenal gland that was completely replaced by tumor, or alternatively, from an accessory adrenal gland (adrenal rest).
A detailed clinicopathologic summary of the reported adrenocortical carcinosarcomas to date, including our case, is provided in Table 2. The age range was 23 to 79 years, with a mean of 49.3 years and a median of 45 years; 8 of 12 patients were younger than 50 years. Seven were female, whereas the remaining 5 were male. The average tumor size was 14.5 cm, with a range of 5 to 24 cm. Most were bulky, ranging from 199 to 6500 g, with an average of 1743 g. At presentation, 7 tumors (58%) either involved the adjacent organs or had already metastasized.
Clinically, 3 (25%) of the 12 reported adrenocortical carcinosarcomas were associated with corticosteroid hyper- secretion, including androstenedione, dehydroepiandroster- one sulfate, testosterone, cortisol, aldosterone, and vanilmandelic acid resulting in hypertension, amenorrhea, virilization, and weight loss [5-7]. Common presentations or complaints were abdominal pain and discomfort (75%). One tumor was found during investigation of a rectal mass in a pregnant patient [12]. Our patient also presented with hypokalemia, abdominal pain, and unintended excessive weight loss of more than 60 lb, although no excess hormonal secretion was documented clinically.
Surgical resection was performed in all cases, and chemotherapy was administered in 6 cases. Two patients received additional radiation therapy for locoregional control. The average postsurgical survival was 6.9 months, with all patients developing metastasis within a few months after surgery (range, 2-5 months) and 10 of 11 dying of disease from 2 days to 14 months after resection.
On light microscopy, 2 of 12 cases showed a pure spindle cell morphology [2,3], whereas the others had both carcinomatous and sarcomatous components. Three of these showed heterologous sarcomatous elements along with an undifferentiated spindle cell sarcoma, whereas another 3 lacked an undifferentiated spindle cell compo- nent, and the remaining 4 did not show any heterologous elements. Of the 6 cases with heterologous elements, 4 displayed rhabdosarcomatous differentiation, one showed an osteosarcomatous component, whereas another had both chondrosarcomatous and osteosarcomatous elements. In- terestingly, the case with osteosarcomatous differentiation was associated with a rectal carcinoma and occurred as a collision tumor containing adrenal carcinosarcoma and rectal adenocarcinoma [12].
It is apparent that adrenocortical carcinosarcoma is highly aggressive. Chemotherapy in addition to surgical resection has shown no clear survival benefits compared with surgical resection alone. Using the Weiss scoring system [14-16] for adrenocortical neoplasms, our case clearly falls in the malignant group because of its high mitotic rate (average, 10/10 HPF), clear cells comprising less than 5%, diffuse architecture greater than one-third of the tumor, necrosis, and invasion of the vasculature. It has, furthermore, been shown that adrenocortical neoplasms showing more than 3 of the Weiss criteria have a shorter disease-free survival and increased relapse risk [17,18], with mitotic rate and atypical mitotic figures the most important predictive factors [15,19]. The case of Thway et al [11] had 2 of the major criteria for malignancy using the modified Weiss scoring system for oncocytic adrenal neoplasms. Given the advanced tumor stage and overall remarkably poor prognosis (survival of <7%), we believe that the other 10 cases of adrenocortical carcinosar- comas would yield similar results if evaluated by this method.
The diagnosis of adrenocortical carcinosarcoma may be especially difficult if the tumor origin is grossly unclear because of large advanced growth at the time of presentation. The differential diagnosis includes sarcomatoid differentia- tion of renal cell carcinoma or urothelial carcinosarcoma. In these situations, immunohistochemical stains for inhibin, calretinin, and Melan-A are useful in establishing adreno- cortical origin as these markers have been established to be highly sensitive for adrenal cortical carcinomas [20-23]. Other cases of adrenocortical carcinosarcomas have also shown, to some degree, positive reactivity with these 3 markers (Table 2). Additional immunohistochemical stains, including low- and high-molecular weight cytokeratins, may be expressed in adrenal cortical neoplasms but are not sensitive or specific.
Adrenocortical carcinosarcoma with variant morphologic features
In summary, we have presented an adrenal carcinosarco- ma with a distinct morphology not previously reported, thus expanding the morphologic spectrum of these rare and highly aggressive neoplasms.
References
[1] Hutter Jr AM, Kayhoe DE. Adrenal cortical carcinoma. Clinical features of 138 patients. Am J Med 1966;41:572-80.
[2] Okazumi S, Asano T, Ryu M, et al. Surgical resection of adrenal carcinoma extending into the vena cava, right atrium and ventricle: case report and review of the literature. Nihon Geka Gakkai Zasshi 1987;88:231-8.
[3] Collina G, Maldarizzi F, Betts CM, Eusebi V. Primary sarcomatoid carcinoma of the adrenal gland. First case report. Virchows Arch A Pathol Anat Histopathol 1989;415:161-7.
[4] Decorato JW, Gruber H, Petti M, Levowitz BS. Adrenal carcinosar- coma. J Surg Oncol 1990;45:134-6.
[5] Fischler DF, Nunez C, Levin HS, McMahon JT, Sheeler LR, Adelstein DJ. Adrenal carcinosarcoma presenting in a woman with clinical signs of virilization. A case report with immunohistochemical and ultrastructural findings. Am J Surg Pathol 1992;16:626-31.
[6] Barksdale SK, Marincola FM, Jaffe G. Carcinosarcoma of the adrenal cortex presenting with mineralocorticoid excess. Am J Surg Pathol 1993;17:941-5.
[7] Lee MS, Park IA, Chi JG, Ham EK, Lee KC, Lee CW. Adrenal carcinosarcoma-a case report. J Korean Med Sci 1997;12:374-7.
[8] Sturm N, Moulai N, Laverriere MH, Chabre O, Descotes JL, Brambilla E. Primary adrenocortical sarcomatoid carcinoma: case report and review of literature. Virchows Arch 2008;452:215-9.
[9] Coli A, Di Giorgio A, Castri F, Destito C, Marin AW, Bigotti G. Sarcomatoid carcinoma of the adrenal gland: a case report and review of literature. Pathol Res Pract 2010;206:59-65.
[10] Sasaki K, Desimone M, Rao HR, Huang GJ, Seethala RR. Adrenocortical carcinosarcoma: a case report and review of the literature. Diagn Pathol 2010;5:51.
[11] Thway K, Olmos D, Shah C, Flora R, Shipley J, Fisher C. Oncocytic adrenal cortical carcinosarcoma with pleomorphic rhabdomyosarco- matous metastases. Am J Surg Pathol 2012;36:470-7.
[12] Bertolini F, Rossi G, Fiocchi F, et al. Primary adrenal gland carcinosarcoma associated with metastatic rectal cancer: a hitherto unreported collision tumor. Tumori 2011;97:27e-30e.
[13] Miettinen M. Neuroendocrine differentiation in adrenocortical carci- noma. New immunohistochemical findings supported by electron microscopy. Lab Invest 1992;66:169-74.
[14] Weiss LM. Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 1984;8:163-9.
[15] Weiss LM, Medeiros LJ, Vickery Jr AL. Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 1989;13:202-6.
[16] Lau SK, Weiss LM. The Weiss system for evaluating adrenocortical neoplasms: 25 years later. HUM PATHOL 2009;40:757-68.
[17] Gicquel C, Bertagna X, Gaston V, et al. Molecular markers and long- term recurrences in a large cohort of patients with sporadic adrenocortical tumors. Cancer Res 2001;61:6762-7.
[18] Tissier F, Louvel A, Grabar S, et al. Cyclin E correlates with malignancy and adverse prognosis in adrenocortical tumors. Eur J Endocrinol 2004;150:809-17.
[19] Assie G, Antoni G, Tissier F, et al. Prognostic parameters of metastatic adrenocortical carcinoma. J Clin Endocrinol Metab 2007;92:148-54.
[20] Ghorab Z, Jorda M, Ganjei P, Nadji M. Melan A (A103) is expressed in adrenocortical neoplasms but not in renal cell and hepatocellular carcinomas. Appl Immunohistochem Mol Morphol 2003;11:330-3.
[21] Pan CC, Chen PC, Tsay SH, Ho DM. Differential immunoprofiles of hepatocellular carcinoma, renal cell carcinoma, and adrenocortical carcinoma: a systemic immunohistochemical survey using tissue array technique. Appl Immunohistochem Mol Morphol 2005;13:347-52.
[22] Jorda M, De MB, Nadji M. Calretinin and inhibin are useful in separating adrenocortical neoplasms from pheochromocytomas. Appl Immunohistochem Mol Morphol 2002;10:67-70.
[23] Zhang PJ, Genega EM, Tomaszewski JE, Pasha TL, LiVolsi VA. The role of calretinin, inhibin, melan-A, BCL-2, and C-kit in differentiating adrenal cortical and medullary tumors: an immunohistochemical study. Mod Pathol 2003;16:591-7.