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A exceptional collision tumor of primary adrenal angiosarcoma and non-functioning adrenocortical adenoma
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Katsumi Takizawaª, Kenichi Kohashib, Takahito Negishic, Kenichi Taguchia, Yuichi Yamadab, Motonobu Nakamurac, Yoshinao Odab,*
a Department of Pathology, National Kyushu Cancer Center, Fukuoka, 811-1395, Japan
b Department of Anatomic pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan
” Department of Urology, National Kyushu Cancer Center, Fukuoka, 811-1395, Japan
ARTICLE INFO
Article history: Received 4 January 2017 Received in revised form 26 March 2017 Accepted 14 April 2017
Keywords: Collision tumor Adrenal angiosarcoma Adrenocortical adenoma
ABSTRACT
Primary adrenal angiosarcoma is an extremely rare vascular tumor. We report a case of a 63-year-old man with a collision tumor of epithelioid angiosarcoma and adrenocortical adenoma of the right adrenal gland. The adrenal tumor was incidentally observed by a preoperative computed tomography (CT) scan of penis squamous cell carcinoma. The patient underwent a right laparoscopic adrenalectomy, and the tumor size measured 34 x 34 x 15 mm. Histological examination revealed two different tumor cell proliferations, namely epithelioid angiosarcoma and adrenocortical adenoma. He had no symptoms or abnormality in his endocrine studies, so the adrenocortical adenoma was considered non-functioning. Three months after the adrenalectomy, bilateral pleural metastasis was observed by CT scan and pleural biopsy. Paclitaxel monotherapy was performed, and the tumor retreated. The patient died one and a half years after the adrenalectomy, but the cause of death was believed to be another disease (metastatic penis squamous cell carcinoma). To the best of our knowledge, this is the fourth report of primary adrenal angiosarcoma combined with adrenocortical adenoma.
@ 2017 Elsevier GmbH. All rights reserved.
1. Introduction
Angiosarcoma is a high-grade malignant neoplasm composed of cells that demonstrate endothelial differentiation [1]. Angiosar- comas commonly occur in the skin, soft tissue, breast, bone, liver and spleen. Primary angiosarcoma of the adrenal gland (PAA) is an extremely rare neoplasm with only 31 cases reported so far in the literature [2-7]. We report herein a case of a collision tumor in which primary adrenal angiosarcoma was combined with adreno- cortical adenoma. To the best of our knowledge, this is the fourth report of primary adrenal angiosarcoma combined with adrenocor- tical adenoma [5-7].
2. Case report
2.1. Clinical presentation
A 66-year-old Japanese man presented with an enlarged tumor of the glans penis. The tumor was diagnosed as squamous cell
carcinoma, so a preoperative examination was done. A computed tomography (CT) scan of the chest and abdomen to search for metastases revealed a 34mm diameter heterogeneous mass of the right adrenal gland (Fig. 1). The lesion was characterized by low density with focal vascularization after intravenous injection of contrast material without evidence of local tissue invasion or metastatic spreading. The lesion was suggestive of cortical ade- noma, but the possibility of malignancy could not be excluded because of the size (diameter >3 cm). He had been diagnosed with high blood pressure two years prior, and had achieved good con- trol (105-125/65-75 mmHg) by 5 mg amlodipine treatment. On physical examination, no other specific findings including obesity were identified. No abnormality was shown in complete blood count or electrolytes. Endocrine studies showed in normal levels of adrenocorticotropic hormone, cortisol, renin, aldosterone and urinary cortisol. First, partial penectomy was performed and the lesion was diagnosed as penis carcinoma, pT3. Pathologically and immunohistochemically, the penis tumor shows well to moder- ately differentiated squamous cell carcinoma, and the carcinoma cells were negative for CD31. Then, two months after the first oper- ation, a laparoscopic right adrenalectomy was performed.
* Corresponding author at: Department of Anatomic Pathology, Pathological Sci- ences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
E-mail address: oda@surgpath.med.kyushu-u.ac.jp (Y. Oda).
3. Pathological findings
Grossly, the adrenocortical tumor appeared well-demarcated, and measured 34 x 34 x 15 mm. The cut surface was yellowish in color and showed focal hemorrhaging (Fig. 2). The residual adrenal gland measured 15 x 17 x 3 mm and was displaced later- ally. Histopathology revealed two different tumor cell components (Fig. 3A). Most of the lesion showed a proliferation of adrenocortical cells without atypia and mitoses, indicating adrenocortical ade- noma (Fig. 3B). The Weiss score was 0 (clear cytoplasmic tumor cells, proliferating in an alveolar pattern, no necrosis, no venous invasion, no sinusoidal invasion, no capsular invasion). Another component within the adrenocortical adenoma showed a prolif- eration of atypical epithelioid cells having oval to polygonal nuclei, prominent nucleoli and eosinophilic cytoplasm, arranged in sheet- like, irregular cord or papillary structures with red blood cells,
invading the surrounding cortical adenoma (Fig. 3C, D). Intracyto- plasmic vacuoles containing red blood cells were observed (Fig. 3E). Mitotic figures were occasionally seen (3/20 HPF).
Immunohistochemically, the atypical epithelioid cells were pos- itive for CD34, CD31, factor VIIIRA, AE1/AE3, ERG, FLI-1 and focally positive for CAM5.2 and vimentin, but negative for D2-40, EMA, calretinin and WT-1 (Fig. 4A,B). The MIB-1 labeling index was about 30% in atypical cell components. Thus, we identified the adrenal lesion as collision tumor, combining epithelioid angiosar- coma within adrenocortical adenoma.
4. Post-operative course
Three months after the adrenalectomy, the patient devel- oped difficulty in breathing. Right pleural effusion and bilateral pleural masses were detected by chest X-ray and CT. These fea- tures were considered bilateral pleural metastases originating from the adrenal angiosarcoma by CT-guided percutaneous biopsy. Paclitaxel monotherapy was used in the four months after the adrenalectomy, and the tumor retreated. One year after the penec- tomy and eleven months after the adrenalectomy, CT revealed
C
A
B
D
E
A
B
| reference | sex | age | size (mm) | clinical type of adenoma | histological type of angiosarcoma | relationship of the two component | chemotherapy result after surgery | |
|---|---|---|---|---|---|---|---|---|
| Lepoutre-Lussey et al. | M | 35 | 60 | functioning | epithelioid | two component were intermingled | AI | alive with no evidence of disase at 2 years |
| Hendry et al. | F | 60 | 55 | non functioning | epithelioid | angiosarcomatous lesion appeared confined within the adrenocortical adenoma | None | alive with no evidence of disase at 9 months |
| Hayashi et al. | M | 63 | 85 | non functioning | epithelioid | two component were intermingled | NA | NA |
| Current case | M | 66 | 34 | non functioning | epithelioid | angiosarcomatous lesion appeared confined within the adrenocortical adenoma | PTX | metastasized to pleura at 3 months died with another disease at 1.5 years |
Abbreviations: NA; not available, AI; adriamycin/ifosfamide, PTX; paclitaxel.
enlarged lymph nodes in the inguinal region and intrapelvic space. The enlarged lymph nodes were diagnosed as metastases from penis squamous cell carcinoma by lymph node biopsy. Recurrence in the inguinal region carries a poor prognosis (median survival <6 months) and optimal management remains elusive by National Comprehensive Cancer Network (NCCN) guideline version 1.2014 penile cancer. The patient discontinued chemotherapy, and pro- ceeded to best supportive care. He died 7 months after the lymph node metastasis was found.
5. Discussion
Angiosarcoma of soft tissue are among the rarest kind of neo- plasms, accounting for a tiny proportion of all vascular tumors, and comprising less than 1% of all sarcomas [8]. They affect patients of all ages and show poor overall survival, with 5-year overall sur- vival rates of 24% to 31%. Deep angiosarcomas commonly have an epithelioid appearance consisting of nests and clusters of round cells of high nuclear grade. These so-called epithelioid angiosarco- mas consist of sheets of highly atypical round cells with prominent nuclei, some of which contain intracytoplasmic lumens. To date, histological features have not been helpful in predicting outcomes in angiosarcomas [8], although there have a few reports suggesting that those with epithelioid features have a worse prognosis than classic-type soft tissue angiosarcomas [9,10].
Primary adrenal angiosarcoma (PAA) is especially rare and difficult to diagnosis. Most adrenal angiosarcomas represent metastases from another primary tumor site. Only 31 cases have been reported in the medical literature [2-7,11]. PAAs occur in adults, with a peak incidence in the sixth decade of life (range
35-85 years old) and have been reported from 3 to 16cm in diameter. PAAs usually present as an isolated adrenal mass either asymptomatic or causing non-specific symptoms like abdominal pain. Endocrine investigations are unremarkable and no definite diagnosis can be made preoperatively. On histopathological exam- ination, most PAAs in the literature are of the epithelioid type. On immunohistochemical analysis, the tumor cells express endothelial markers CD31, CD34,von Willebrand factor (factor VIII), ERG and FLI-1. The tumor often shows positive immunostaining for epithe- lioid markers, especially in epithelioid areas of the tumor; hence, epithelioid angiosarcoma can be misdiagnosed as carcinoma. Direct infiltration of the kidney, gastric wall, intestinal loop, pancreas, spleen, contralateral adrenal gland, and pulmonary metastases have been reported [4]. The treatment of choice is surgical excision. Chemotherapy should be considered only in cases of distinct metas- tases. Of the 21 cases reported in the literature, nine patients were alive with no disease after surgery, one case was discovered acci- dentally at autopsy, one patient died of unrelated causes, five died of postoperative complications, and the remaining five patients died of disease [2-6,11].
In this case, the differential diagnosis includes epithelioid hemangioendothelioma, adrenal cortical carcinoma and metastatic tumor. The most reliable clues for differentiation are provided by careful examination by light microscopy combined with the immunohistochemical pattern of staining. Epithelioid heman- gioendotheliomas express typical vascular markers (including CD34 and CD31) and have myxohyaline stroma. This case expressed typical vascular markers, but no myxohyaline stroma, and the tumor cells were higher-grade neoplasms with brisk mitotic activ- ity and significant nuclear atypia rather compared to epithelioid
hemangioendothelioma. Because epithelioid angiosarcomas co- express epithelial antigens, cytokeratin reactivity is not useful in distinguishing them from carcinoma.
This case is the fourth reported instance of a collision tumor of angiosarcoma and adrenocortical adenoma (Table 1). Compared with the first case (described by Lepoutre-Lussey et al. [5]), our patient was older and had no symptoms or serum abnormality. Incidentally the lesion was discovered accidentally by computed tomography, a so-called “incidentaloma” [12]. In the current case, the size of angiosarcomatous lesion was 1.8 mm. PAAs are usu- ally > 6 cm in diameter, so that this lesion was much smaller than average size. On histopathological examination, in the first case, angiosarcomatous lesion and adrenocortical adenomatous lesion were intermingled. In the current case, the angiosarcomatous lesion presented as a mass with invasion of the surrounding cortical adenomatous area. The features suggested epithelioid angiosar- coma arising in cortical adenoma. The angiosarcomatous lesion appeared to be covered by the adenomatous lesion, and the adreno- cortical adenoma appeared to be encapsulated. These features are similar to the case described by Hendry et al. [6], who suggested that the angiosarcoma arose from vascular elements within the adrenal cortical adenoma. While the precise mechanism involved in the development of these collision tumor is uncertain at present, the rich vasculature of endocrine lesions may serve as a favor- able milieu for neoplastic transformation of endothelial cells as described by Hayashi et al. [7]. On the other hand, exposure to arsenicals or vinyl chloride was reported to be predisposing fac- tors of adrenal angiosarcoma [13,14], but it seems likely that such factors are not involved in the current case because the patient in this study has not been exposed to such factors. More case investigations are necessary to better understand the biolog- ical characteristics and clinical outcomes of this unusual collision tumor.
Angiosarcomas are very aggressive, but a long survival may occasionally be observed in PAAs after complete excision. No opti- mal adjuvant chemotherapy has yet been clearly identified. This case is a rare case in which paclitaxel was successfully used to treat pleural metastasis. The patient died one and a half years after the adrenalectomy. Clinically, the cause of death was ascribed to the other disease (metastatic penis squamous cell carcinoma), but not conclusively because of the lack of detailed examination and autopsy.
Conflict of interest statement
All authors have no conflict of interest related to this study. There is no funding support to disclose.
References
[1] S.W. Weiss, C.R. Antonescu, A.T. Deyrup, Angiosarcoma of soft tissue, in: C.D. Fletcher, J.A. Bridge, P.C. Hogendoorn, F. Mertens (Eds.), World Health Organization Classification of Tumors, WHO Classification of Tumors of Soft Tissue and Bone, IARC Press, Lyon, 2013, pp. 156-158.
[2] J.Y. Sung, S. Ahn, S.J. Ki, Y.S. Park, Y.L. Choi, Angiosarcoma arising within a long-standing cystic lesion of the adrenal gland: a case report, J. Clin. Oncol. 31 (2013) e132-136.
[3] L. Galmiche, H.P. Morel, A. Moreau, P.A. Labrosse, J.M. Coindre, M.F. Heymann, Primary adrenal angiosarcoma, Ann. Pathol. 24 (2004) 371-373.
[4] E. Pasqual, F. Bertolissi, F. Grimaldi, C.A. Beltrami, C.A. Scott, B. acchetti S, B.U. Waclaw, P.P. Cagol, Adrenal angiosarcoma: report of a case, Surg. Today 32 (2002) 563-565.
[5] C. Lepoutre-Lussey, A. Rousseau, A. Al Ghuzlan, L. Amar, C. Hignette, A. Cioffi, F. Zinzindohoué, S. Leboulleux, P.F. Plouin, Primary adrenal angiosarcoma and functioning adrenocortical adenoma: an exceptional combined tumor, Eur. J. Endocrinol. 166 (2012) 131-135.
[6] S. Hendry, C. Forrest, Epithelioid angiosarcoma arising in an adrenal cortical adenoma: a case report and review of the literature, Int. J. Surg. Pthol. 22 (2014) 744-748.
[7] T. Hayashi, H. Gucer, O. Mete, A mimic of sarcomatoid adrenal cortical carcinoma: epithelioid angiosarcoma occurring in adrenal cortical adenoma, Endocr. Pathol. 25 (2014) 404-409.
[8] J.R. Goldblum, A.L. Folpe, S.W. Weiss, Enzinger and Weiss’s SOFT TISSUE TUMORS, 6th ed. Missouri, Mosby, 2014, pp. 703-722.
[9] G. Lahat, A.R. Dhuka, H. Hallevi, L. Xiao, C. Zou, K.D. Smith, T.L. Phung, R.E. Pollock, R. Benjamin, K.K. Hunt, A.J. Lazar, D. Lev, Angiosarcoma; clinical and molecular insights, Ann. Surg. 251 (2010) 1098-1106.
[10] A.T. Deyrup, J.K. McKenney, M. Tighiouart, A.L. Folpe, S.W. Weiss, Sporadic cutaneous angiosarcoma: a proposal for risk stratification based on 69 cases, Am. J. Surg. Pathol. 32 (2008) 72-77.
[11] A.G. Croitoru, A.P. Klausner, G. McWilliams, P.D. Unger, Primary epithelioid angiosarcoma of the adrenal gland, Ann. Diagn. Pathol. 5 (2001) 300-303.
[12] M.M. Grumbach, B.M. Biller, G.D. Braunstein, K.K. Campbell, J.A. Carney, P.A. Godley, E.L. Harris, J.K. Lee, Y.C. Oertel, M.C. Posner, J.A. Schlechte, H.S. Wieand, Management of the clinically inapparent adrenal mass (incidentaloma), Ann. Intern. Med. 138 (2003) 424-429.
[13] A. Livaditou, G. Alexiou, D. Floros, T. Filippidis, T. Dosios, D. Bays, Epithelioid angiosarcoma of the adrenal gland associated with chronic arsenical intoxication, Pathol. Res. Pract. 187 (1991) 284-289.
[14] M. Criscuolo, J. Valerio, M.E. Gianicolo, E.A. Gianicolo, M. Portaluri, A vinyl chloride-exposed worker with an adrenal gland angiosarcoma: a case report, Ind. Health 52 (2014) 66-70.