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Primary adrenal leiomyosarcoma: A case report with immunohistochemical study and review of literature

ABSTRACT Sanjay D. Primary adrenal mesenchymal tumors are exceptionally rare. Diagnosis is based entirely on histological and immunohistochemical Deshmukh, evaluation which is indispensable not only for determining tumor type but also for predicting biological behavior. We report a rare case Shridhar V. of primary leiomyosarcoma of the left , in a 60 year old woman who presented with flank pain. Computed tomography Babanagare, revealed a well defined left which was surgically resected. Histological examination of the tumor showed malignant Mani Anand, 1 spindle cells in interlacing fascicles and whorls. Nuclear pleomorphism, tumor giant cells and abnormal mitotic figures were seen. Dilip P. Pande , On immunohistochemistry, the tumor cells showed reactivity for smooth muscle actin, and ; and were negative for Prasanna 1 , , CD117 and HMB-45. A diagnosis of primary adrenal leiomyosarcoma was offered. Postoperative recovery of Yavalkar the patient was uneventful and the patient was symptom free with no evidence of tumor metastasis or recurrence 21 months after surgery. Departments of Pathology and 1Surgery, Smt. KEY WORDS: Adrenal gland, Adrenal leiomyosarcoma, Leiomyosarcoma, Immunohistochemistry Kashibai Navale Medical College and General Hospital, Narhe, Pune, INTRODUCTION and blood pressure of 120/80 mm Hg. There was no Maharashtra, India evidence of pedal edema or lymphadenopathy. On Primary adrenal sarcomas are exceptionally per abdominal examination, a 5 × 4 × 3 cm mass For correspondence: uncommon and include leiomyosarcoma, malignant was palpated in the left hypochondrium. The mass Dr. Sanjay. D. Deshmukh, peripheral nerve sheath tumor (MPNST) and was firm, non-tender, non ballotable and did not Department of [1] angiosarcoma. Reviewing the literature, we move with respiration. There was no evidence of Pathology, encountered only twelve previously reported cases hepatosplenomegaly or ascites. Routine laboratory Smt. Kashibai Navale [2] of primary adrenal leiomyosarcoma (PAL). We investigations were non contributory. The 24 hours Medical College and believe that this is the thirteenth case of PAL. It General Hospital, urinary vanillylmandelic acid level was within Narhe, Pune, has a wide range of differential diagnosis including normal limits. HIV-1 and HIV-2 antibody tests were Maharashtra, India. MPNST, malignant melanoma, gastrointestinal non-reactive, as was HBsAg. Liver function tests, E-mail: drsanjay- stromal tumour (GIST); metastatic serum amylase and CA-19.9 were [email protected] and others. A complete workup including also within normal limits. radiological, biochemical, histomorphological and immunohistochemical investigation is essential Computed Tomography (CT) scan of the abdomen for the final diagnosis of PAL. We encountered a revealed a well defined soft tissue lesion measuring rare case of PAL fulfilling the clinico-radiological 5.2 × 4.5 × 3.8cm in the left upper abdomen and histomorphologicaland immunohistochemical posterior to the body of the pancreas and anterior criteria, which has prompted us to report this case. to the left , showing heterogeneous CASE REPORT enhancement on contrast. The mass was thought to be a lymphoid or a pancreatic mass [Figure 1]. Access this article online Clinical history Careful clinical and radiological examination did not reveal any other primary tumor site or Website: www.cancerjournal.net A 60 year old lady presented with a 5 month DOI: 10.4103/0973-1482.110394 history of left upper quadrant abdominal mass distant metastasis. Exploratory laparotomy was PMID: *** which was painful and gradually increasing in performed. A retroperitoneal mass arising from the Quick Response Code: size. She denied any history of fever, weight loss, left adrenal gland was seen which was dissected nausea or vomiting. Past medical, surgical or and excised. Post-operative course was uneventful family history was non-contributory. On general and the patient was symptom free with no evidence physical examination, the patient was averagely of recurrence or distant metastasis 21 months after built and nourished. She had a pulse of 64/minute surgery.

114 Journal of Cancer Research and Therapeutics - January-March 2013 - Volume 9 - Issue 1 Deshmukh, et al.: Adrenal leiomyosarcoma Pathological examination (CK) (clone AE-1/AE-3, Dako), HMB-45 (clone HMB-45, Dako), On Gross Examination the tumor was a 5.2 × 4.5 × 3.8 cm, smooth muscle actin (SMA) (clone 1A4 Dako), desmin (clone thinly encapsulated firm mass with a bosselated appearance 33, Biogenex), S100 protein (polyclonal S100A4, Dako), CD117 almost completely replacing the adrenal gland [Figure 2]. On (clone T595, Novacastra), CD34 (clone QBEnd/10, Novacastra). sectioning, the cut surface revealed uniform, grey white color The neoplastic cells showed strong cytoplasmic reactivity with streaks and strands and a whorled appearance in places. for smooth muscle actin [Figure 4a], desmin [Figure 4b] It did not show areas of hemorrhage or necrosis. and vimentin. They were negative for CK, S100 protein, CD117 and HMB-45 and CD34. Based on these findings, final diagnosis On microscopic examination the adrenal mass showed a thinly of primary leiomyosarcoma of the adrenal gland was offered. encapsulated tumor composed of spindled neoplastic cells arranged in interlacing bundles and fascicles of varying sizes. DISCUSSION The individual cells showed moderate eosinophilic cytoplasm and cigar shaped nuclei with dispersed chromatin. Primary adrenal mesenchymal tumors are exceptionally rare, and are thought to arise from the smooth muscle wall of At the periphery of the tumor, part of the normal appearing the central adrenal vein and its tributaries.[3] A review of the adrenal cortex was identified from which the tumor was literature revealed only twelve previously reported cases of arising [Figure 3a]. The tumor showed nuclear pleomorphism, PAL.[2] The reported age of patients ranged from 30 to 75 years giant cell formation and 10 to 12 abnormal mitotic figures per with approximately equal frequency in males and females. 10 high power fields [Figure 3b]. The stroma showed numerous All these tumors ranged in size from 11 to 25 cm in greatest congested blood vessels; however, no areas of necrosis or dimension.[4] In only one case report, the tumor was 3 cm in lymphovascular invasion were identified. size.[5] It is worth mentioning that our patient was HIV and HBsAg negative. Immunohistochemical findings Immunohistochemistry was performed with the following primary antibodies - vimentin (Clone V-9, Biogenex), cytokeratin

Figure 2: Macroscopic features of tumor (external and cut surface) - External surface showed a thinly encapsulated firm tumor having a bosselated surface. The mass was grey white in color and measured Figure 1: Pre-operative Abdominal CT scan - It shows tumor mass 5.2 × 4.5 × 3.8 cm. The cut surface revealed a tumor which was uniform, anterior to the left kidney, arising from the left adrenal gland grey white in color and showed streaks and strands of tumor tissue with whorled appearance at places

a b Figure 3: (a) Microscopic details of tumor - Interlacing bundles a b and fascicles of tumor along with part of adrenal tissue (arrow). Figure 4: Immunohistochemical findings –(a) Tumor cells showing (H and E, × 100).(b) Microscopic details of tumor - Leiomyosarcoma strong immunoreactivity for smooth muscle actin (SMA) (× 400), and with nuclear pleomorphism and giant cell formation. (H and E, × 400) (b) immunoreactivity for desmin (× 400)

Journal of Cancer Research and Therapeutics - January-March 2013 - Volume 9 - Issue 1 115 Deshmukh, et al.: Adrenal leiomyosarcoma In the differential diagnosis of the present tumor we comparable to the longest disease free survival reported.[10] considered: metastatic carcinoma; metastatic sarcoma; MPNST; In conclusion, diagnosis of leiomyosarcoma of adrenal gland malignant melanoma; GIST and primary retroperitoneal is one of exclusion and is based on radiological, biochemical, sarcoma infiltrating into the adrenal gland. A primary adrenal histomorphological and immunohistochemical evaluation. tumor was favored over a metastatic tumor because of the PALs carry a poor prognosis when morphologically they are unilateral involvement of adrenal gland and lack of cytokeratin large in size andhistologically show lymphovascular invasion expression. Distinct demarcation of the present tumor from and high grade nuclear features throughout the tumor in such the surrounding structures by an intact capsule ruled out the cases judicious use of radiotherapy and chemotherapy may possibility of extra-adrenal sarcoma extending into the adrenal be contemplated; however, complete surgical resection is of gland. Lack of S100 protein expression and strong SMA and paramount importance in their treatment. We believe that desmin positivity favored the diagnosis of leiomyosarcoma low grade features, absence of lymphovascular invasion and over MPNST. Malignant melanoma would express HMB-45 necrosis, favor long term survival after aggressive surgical and/or S100 protein. Lack of expression of CD117 ruled out resection. GIST. Taking into consideration the above findings coupled with radiological and clinical observations, a final diagnosis REFERENCES of PAL was made. 1. RosaiJ. Adrenal gland and other paraganglia. In: RosaiJ, editor. th Histologically, smooth muscle tumors containing 5 or Rosai and Ackerman’s Surgical Pathology. 9 ed. Edinburgh, Scotland: Mosby; 2004. p. 1115-62 more mitoses per 50 high power fields are classified as 2. Mencoboni M, Bergaglio M, Truini M, Varaldo M. Primary adrenal malignant. The presence of tumor cell necrosis is also leiomyosarcoma: A case report and literature review. Clin Med Oncol strongly suggestive of malignancy.[6] In the present case 2008;2:353-6. however, necrosis and lymphovascular invasion was absent. 3. Lack EE, Graham CW, Azumi N, Bitterman P, Rusnock EJ, O’Brien W, Apart from the usual spindle cell type leiomyosarcomas, et al. Primary leiomyosarcoma of adrenal gland. Case report with pleomorphic leiomyosarcomas have been described. These immunohistochemical and ultrastructural study.Am J Surg Pathol 1991;15:899-905. tumors show numerous pleomorphic giant cells intimately 4. Lujan MG, Hoang MP. Pleomorphic Leiomyosarcoma of the adrenal admixed with a component of more uniform appearing gland. Arch Pathol Lab Med 2003;127:32-5. spindle and round neoplastic cells, bizarre mitotic figures 5. Lee CW, Tsang YM, Liu KL. Primary adrenal Leiomyosarcoma. and irregular zones of necrosis.[4,6] Our case was interpreted Abdom Imaging 2006;31:123-4. as conventional low gradeleiomyosarcoma due to absence 6. RosaiJ. Peritoneum, retroperitoneum, and related structures. of necrosis, absence of lymphovascular invasion and relative In:RosaiJ, editor. Rosai and Ackerman’s Surgical Pathology. 9th ed. Edinburgh, Scotland: Mosby; 2004. p. 2373-415. paucity of bizarre pleomorphic neoplastic cells. This explains 7. Rosenthal JT, Colonna JO, Drinkwater DC. Leiomyosarcoma of the relatively long term survival in our patient and highlights vena cava with atrial extension: Long-term survival following the careful documentation of histomorphological features. resection and caval replacement without circulatory arrest. Urology It is worth noting that long term survival over 3 years has 1995;46:876-8. been documented in leiomyosarcoma without chemotherapy 8. Etten B, van I jken MG, Mooi WJ, Oudkerk M, van Geel AN. Primary Leiomyosarcoma of the adrenal gland. Sarcoma 2001;5:95-9. or radiotherapy in a case arising from inferior vena cava.[7] 9. Shmookler BM, Lauer DH. Retroperitoneal leiomyosarcoma: A clinicopathologic analysis of 36 cases. Am J Surg Pathol 1983;7: Histological evaluation is indispensable not only for 269-80. determining tumor type but also for grading and predicting 10. Zetler PJ, Filipenko JD, Bilbey JH, Schmidt N. Primary adrenal biological behavior.[8,9] Conventional leiomyosarcomas Leiomyosarcoma in a man with acquired immunodeficiency invariably show reactivity for smooth muscle markers such syndrome (AIDS). Further evidence for an increase in smooth muscle tumors related to Epstein-Barr infection in AIDS. Arch Pathol Lab as smooth muscle actin and/or muscle specific actin in 90 to Med 1995;119:1164-7. 95 %, and desmin in 70-90% of the cases.[3,4,9,10]

Cite this article as: Deshmukh SD, Babanagare SV, Anand M, Pande PALs carry a poor prognosis; with the longest disease free DP, Yavalkar P. Primary adrenal leiomyosarcoma: A case report with survival being 20 months.[10] Our patient did not have any immunohistochemical study and review of literature. J Can Res Ther metastasis 21 months after surgery and we are following 2013;9:114-6. the case with sustained enthusiasm, this follow up period is Source of Support: None, Conflict of Interest: None.

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