IJSXXX10.1177/1066896914526777International Journal of Surgical PathologyWei et al
Primary Adrenal Leiomyosarcoma: Case Report and Review of the Literature
International Journal of Surgical Pathology 2014, Vol. 22(8) 722–726 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1066896914526777 ijs.sagepub.com
Jianguo Wei, MD1, Aijing Sun, MD, PhD1, Jian Tao, MD1, Cheng Wang, MD, PhD1, and Fang Liu, MD1
Abstract Primary adrenal leiomyosarcoma is a very rare tumor with an unusual location; the diagnosis is based entirely on histological and immunohistochemical evaluations. We report a primary adrenal leiomyosarcoma in a 57-yearold woman who was incidentally found to have an adrenal-occupying lesion during a routine medical examination. Computed tomography revealed a 64 mm × 77 mm soft tissue mass in the left adrenal gland. The patient underwent left radical nephroadrenalectomy. Histological examination of the tumor showed malignant spindle cells in interlacing fasicles and whorls. Nuclear pleomorphism, tumor giant cells, necrosis, and abnormal mitotic figures were present. On immunohistochemistry, the tumor cells were strongly positive for smooth muscle actin, desmin, and vimentin expression, but negative for cytokeratin, CD117, CD34, CD68, Myoglobin, S100, and HMB-45.The final histopathological diagnosis was primary adrenal leiomyosarcoma. Keywords adrenal gland, adrenal tumor, leiomyosarcoma, immunohistochemistry
Introduction Leiomyosarcoma is a relatively rare soft-tissue tumor that can arise from any structure or organ containing smooth muscle. Primary adrenal leiomyosarcoma most likely originates from smooth muscle in the central adrenal vein or its tributaries.1 Here we describe an asymptomatic patient who was found to have an adrenal-occupying lesion during a routine medical examination. The histopathological and immunohistochemical features of the excised tumor were characteristic of leiomyosarcoma, which was thought to originate in the left adrenal gland. We also present a brief review of primary adrenal leiomyosarcoma, including clinical and histopathological features, biologic behavior, clinical prognosis, and diagnostic and therapeutic approaches.
Case Report A 57-year-old woman with type 2 diabetes mellitus and with no other notable medical history was incidentally found to have an adrenal-occupying lesion during a medical examination at Shaoxing People’s Hospital in September 2009. Physical examination revealed a healthy looking woman with no obvious signs. Routine laboratory investigations were normal, including complete blood count and serum urea and electrolyte levels. All the hormonal data, including blood levels of aldosterone, cortisol, and catecholamines, were within normal limits. Tumor
markers, including carcinoembryonic antigen, α-fetoprotein, and carbohydrate antigen 19-9, were all within normal limits. Gray-scale sonography revealed a large solid mass (63 mm × 60 mm) in the upper abdomen, mostly in the left upper abdominal quadrant. The mass appeared well marginated, homogeneous, and diffusely hypoechoic with no identifiable necrotic or cystic areas. The patient subsequently underwent abdominal computed tomography (CT); CT findings revealed a 64 mm × 77 mm soft tissue mass involving the left adrenal with slight peripheral enhancement pattern with contrast (Figure 1A and B). After injection of contrast, areas of mild enhancement were seen. There was no evidence of neoplasia in other abdominal organs or lymph nodes. CT of the chest and brain, chest X-ray, and bone scintigraphy were negative. Excretory urography showed a normal left kidney. The patient was advised to undergo radical excision of the left adrenal mass. Surgery revealed a left adrenal tumor adherent to the renal vein and the posterior wall of the stomach. The left kidney was not involved. Our patient 1
Shaoxing People’s Hospital, Shaoxing, Zhejiang Province, People’s Republic of China Corresponding Author: Jianguo Wei, Department of Pathology, Shaoxing People’s Hospital, No. 568 Zhongxing North Road, Shaoxing District, 312000 Shaoxing, Zhejiang Province, People’s Republic of China. Email: [email protected]
Wei et al
Figure 1. CT findings revealed a 64 mm × 77 mm soft tissue mass involving the left adrenal with slight peripheral enhancement pattern with contrast (A and B).
Figure 2. Microscopically, normal-appearing adrenal cortex from which the tumor was arising was identified at the periphery of the tumor (A; hematoxylin–eosin [H&E], 25×). The tumor consisted of spindle cells arranged in interlacing fascicles (B; H&E, 50×); in some areas, the appearance of neoplastic cells ranged from spindled to plump, and the cells had cigar-shaped (C; H&E, 100×), blunt-ended nuclei. The tumor showed nuclear pleomorphism, giant cell formation (D; H&E, 100×).
had a local recurrence 17 months after surgery and underwent a second operation.
Pathological Examination On gross examination, the excised specimen measured 80 mm × 75 mm × 55 mm; cross-sections of the tumor revealed a firm, grayish white mass surrounded by a thin fibrous pseudocapsule, with focal areas of hemorrhage.
There was grossly identifiable adrenal gland tissue around the tumor. Microscopically, normal-appearing adrenal cortex from which the tumor was arising was identified at the periphery of the tumor (Figure 2A). The tumor consisted of spindle cells arranged in interlacing fascicles (Figure 2B); in some areas, the appearance of neoplastic cells ranged from spindled to plump, and the cells had cigarshaped (Figure 2C), blunt-ended nuclei. The tumor showed nuclear pleomorphism, giant cell formation (Figure 2D),
International Journal of Surgical Pathology 22(8)
Figure 3. Immunohistochemically, neoplastic cells were strongly reactive for smooth muscle actin (A; EnVision, 50×) and desmin (B; EnVision, 50×).
with more than 10 abnormal mitotic figures per 50 highpower fields and large areas of necrosis. Immunohistochemically, neoplastic cells were strongly reactive for smooth muscle actin (SMA; Figure 3A), desmin (Figure 3B), and vimentin, but were negative for cytokeratin (CK), CD117, S100, CD68, HMB45, Myoglobin, and CD34. Epstein–Barr virus (in situ hybridization) was negative. The final histological diagnosis was primary adrenal leiomyosarcoma.
Discussion Leiomyosarcoma is a soft tissue tumor that develops from smooth muscle and is a relatively rare tumor that arises mainly in the retroperitoneal space and abdominal cavity. Primary adrenal leiomyosarcoma is an extremely rare malignant tumor2; to the best of our knowledge, only 20 cases of primary adrenal leiomyosarcoma have been previously reported in the English-language literature. The previously reported cases of adrenal leiomyosarcoma are summarized in Table 1. This tumor is thought to arise from smooth muscle in the central adrenal vein or its tributaries. While the exact etiology of an adrenal leiomyosarcoma may not be known, it is of interest that 4 cases have been associated with acquired immunodeficiency syndrome and 2 cases with Epstein-Barr virus (EBV) infection.5 Therefore, it appears that this tumor is likely to occur in immunosuppressed patients. However, other reports did not mention the adrenal leiomyosarcoma associated with HIV and EBV. Our patient was negative for HIV, EBV, and HBsAg; therefore, we hypothesized that there was no direct relationship between them. The ages of all the patients reported ranged from 14 to 75 years, indicating that the tumor has been principally found in adults, most of them were elderly.1,2,11-15 Males and females have been approximately equally affected, with the tumors occurring approximately at the same rate on either side. Most of the tumors have been unilateral;
only 2 patients had bilateral tumors.12,17 Tumors were larger than 8 cm in diameter in 63.2% of cases; there have only been a few cases where the tumors were 3 cm and presented as a mass in the abdomen or ﬂank.14 There are no tumor markers or imaging characteristics that allow a preoperative diagnosis, and all cases have been diagnosed after surgical resection or at necropsy. The diagnosis is based entirely on histopathological and immunohistochemical evaluations. The tumor of our patient showed a typical fascicular growth pattern with spindle cells intersecting at right angles, and there were some areas with diffuse pleomorphic neoplastic cells containing large nuclei. There were also areas with features mimicking undifferentiated pleomorphic sarcoma, because of the presence of osteosclast-like giant cells. The tumor cells were positive for SMA, desmin, and vimentin expression. Therefore, the final diagnosis was adrenal leiomyosarcoma. Histological evaluation is indispensable for grading and predicting biological behavior of primary adrenal leiomyosarcoma. Survival mainly depends on the feasibility of complete resection, tumor size, location, and morphologic grading (nuclear atypia, mitotic activity, and extent of necrosis). Our case was interpreted as a high-grade leiomyosarcoma, because the tumor contained a large amount of necrosis, pleomorphic neoplastic cells, and high mitotic activity, in addition to adhering to the renal vein and wall of the stomach. The patient developed local recurrence 17 months after the initial resection. There was not much difference in the histopathological features between the primary tumor and the recurrent tumor. The differential diagnosis included primary retroperitoneal sarcoma with direct invasion of the adrenal gland, metastatic carcinoma, sarcomatoid renal carcinoma, adrenocortical carcinoma, malignant melanoma, angiosarcoma, malignant peripheral nerve sheath tumor (MPNST), and gastrointestinal stromal tumor (GIST). A metastatic lesion usually involves both adrenal glands, and a primary
Wei et al Table 1. Clinicopathologic Characteristics of Previously Reported Cases of Adrenal Leiomyosarcoma. Author/Reference
Metastatic Lesion or Local Extension
Choi and Liu
Lack et al4
None (preoperative) Bone(postoperative after 3 months)
Zetler et al5
Adrenalectomy + nephrectomy; chemotherapy + radiation therapy Adrenalectomy
Boman et al,6 case 1 Boman et al,6 case 2 Kato et al7
48 29 59
Malea Malea Male
Right Left Left
2 0.8 10
Lujan and Hoang8
None None None (preoperative); bone and liver (postoperative after 1 months) Lung and liver metastasis
CandanedoGonzález et al9
Mohanty et al10
Wang et al11
Hamada et al12
Mencoboni et al13
Lee et al14
Shao et al1
Deshmukh et al2
Right (8); left (4)
None (preoperative); local recurrence and liver metastases (postoperative after 12 months) None (preoperative); lung and liver metastases (postoperative after 9 months) IVC thrombus and extending into atrium
None (autopsy) None (autopsy) Adrenalectomy + nephrectomy + thrombectomy + radiation Adrenalectomy + preoperative chemotherapy Adrenalectomy Chemotherapy + radiation
Dead shortly after surgery 24 (alive without metastasis and recurrence)
Adrenalectomy + thrombectomy
12 (alive without metastasis and recurrence) 16 (dead)
Renal vein thrombus
Adrenalectomy + thrombectomy
Etten et al15 Lujan and Hoang8
Fixed to the liver None
Laparotomy only Adrenalectomy + nephrectomy
Matsui et al16
Linos et al17
Adrenalectomy + nephrectomy + thrombectomy Bilateral adrenalectomy
Goto et al18
Jianguo et al (current case)
20 (alive without metastasis and recurrence) Not determined Not determined 6 (dead)
9 (alive with lung and liver metastasis)
Bilateral adrenalectomy Chemotherapy + radiation + radiofrequency ablation Adrenalectomy
12 (alive without metastasis and recurrence) 9 (alive with bone metastasis)
None (preoperative) Multiple metastasis (postoperative) IVC thrombus
Right (3.5); left (4) 8
Adrenalectomy + nephrectomy
None (preoperative); recurrence (postoperative after 17 months)
Adrenalectomy; tumor resection + chemotherapy
12 (alive without metastasis and recurrence) 10 (alive without metastasis and recurrence) 18 (alive without metastasis and recurrence) 21 (alive without metastasis and recurrence) Died after 3 weeks 12 (alive without metastasis and recurrence) 1 (dead) Not determined 10 (alive without metastasis and recurrence) 29 (alive without metastasis and recurrence)
HIV infection. Epstein–Barr virus infection.
adrenal tumor was thought more likely because the tumor had completely replaced the left adrenal gland, with no invasion of the kidney or the adjoining soft tissue. The tumor had a thin fibrous capsule, which ruled out a primary retroperitoneal sarcoma.
The lack of CK expression ruled out metastatic carcinoma and sarcomatoid renal carcinoma. The lack of S100 protein expression ruled out MPNST. The lack of S100 and HMB-45 protein ruled out malignant melanoma, lack of CD117 expression ruled out GIST, and lack of CD34
726 expression ruled out angiosarcoma. The tumor of our patient also had areas that resembled MHF, which is usually positive for CD68 expression. In our case, the final diagnosis of leiomyosarcoma was supported by histopathological findings plus the positive immunostaining for SMA and desmin, and radiological and clinical observations. Radical surgical resection is said to be the only suitable treatment for adrenal leiomyosarcoma. Some reports have suggested that radiation therapy and chemotherapy are beneficial; however, the evidence has not been conclusive.19,20 The prognosis is extremely poor, and most patients have local recurrence or distant metastasis. Identification of the tumor at an early stage is difficult because symptoms are usually not obvious. Our patient was incidentally found to have an adrenal-occupying lesion during a medical examination, and the tumor was identified at a relatively early stage, so after the adrenalectomy, the patient was not given any treatment; however, the patient developed a local recurrence 17 months after surgery. The patient had a second operation and received adjuvant chemotherapy (vincristine, isofosfamide, and adriamycin), and she had no local recurrence or metastasis after 29-month follow-up. In conclusion, an adrenal mass with spindle cells and bizarre pleomorphic cells should raise the suspicion of leiomyosarcoma. Because the prognosis is extremely poor, ancillary studies and correlation with clinical findings are needed for appropriate evaluation of these rare cases. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
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