Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 7501
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size

  Table of Contents    
Year : 2014  |  Volume : 57  |  Issue : 1  |  Page : 130-132
Malignant peripheral nerve sheath tumor of adrenal gland with heterologus osseous differentiation in a case of Von Recklinghausen's disease

1 Department of Pathology, Apollo Hospital, Bhubaneswar, Odisha, India
2 Department of Urology, Apollo Hospital, Bhubaneswar, Odisha, India

Click here for correspondence address and email

Date of Web Publication17-Apr-2014


Malignant peripheral nerve sheath tumor (MPNST) of the adrenal gland is extremely rare. Most of them occur in association with neurofibromatosis, ganglioneuroma or as part of a composite tumor such as pheochromocytoma. Only seven cases of MPNST of the adrenal gland have been reported in the literature till date. Discriminating this entity from other soft tissue sarcomas and gastrointestinal stromal tumor of the adrenal gland has important diagnostic and therapeutic implications. Moreover, the tumor size and pattern of expression for certain immunohistochemical markers may serve as independent predictors of aggressiveness. Herein we present a 24-years-old male with features of Von Recklinghausen's disease who presented with large left adrenal gland malignant peripheral nerve sheath tumor.

Keywords: Adrenal gland, malignant peripheral nerve sheath tumor, neurofibromatosis, von Recklinghausen′s Disease

How to cite this article:
Baisakh MR, Mohapatra N, Adhikary SD, Routray D. Malignant peripheral nerve sheath tumor of adrenal gland with heterologus osseous differentiation in a case of Von Recklinghausen's disease. Indian J Pathol Microbiol 2014;57:130-2

How to cite this URL:
Baisakh MR, Mohapatra N, Adhikary SD, Routray D. Malignant peripheral nerve sheath tumor of adrenal gland with heterologus osseous differentiation in a case of Von Recklinghausen's disease. Indian J Pathol Microbiol [serial online] 2014 [cited 2021 Sep 22];57:130-2. Available from: https://www.ijpmonline.org/text.asp?2014/57/1/130/130924

   Introduction Top

Malignant peripheral nerve sheath tumor (MPNSTs) arises from major nerve trunks and frequently involves the proximal portion of the upper and lower extremities and the trunk. MPNST of the adrenal gland is of rare occurrence. All reported cases are associated with neurofibromatosis, pheochromocytoma, or ganglioneuroma. [1],[2],[3],[4],[5],[6] Von Recklinghausen's disease (Neurofibromatosis type 1) is an autosomal dominant disorder designated as neurocristopathy by Bolande (1974), based on the concept of origin of various tumors from developmental arrests and maldevelopment of totipotential neural crest cells. [7] Various solid tumors associated with neurofibromatosis type 1 presenting as abdominal mass are pheochromocytoma, rhabdomyosarcoma and MPNST. [8] We present a 24-years male with features of Von Recklinghausen's disease and MPNST of left adrenal gland with heterologous differentiation.

   Case Report Top

A 24-years-old male patient was presented with history of dull aching pain in the left flank. On examination, patient had multiple neurofibromas and café au lait macules all throughout the body. He also had kyphoscoliosis. The hematologic parameters, relevant biochemical parameters including urinary Vanillyl mandelic acid level were within normal limit. Other metabolic evaluations for the functionality of the tumor were normal. Computed tomographic scans of the abdomen [Figure 1] showed an enlarged mass in the left adrenal gland, which measured 16 cm in maximum dimension. The mass was displacing the left kidney and the spleen. All major vessels were shifted beyond midline. He underwent open left adrenal mass excision through a left thoracoabdominal approach.

On gross examination, the entire adrenal gland was replaced by the tumor, which measured 15 12 11 cm 3 ; the capsular surface was smooth and tan-white. The cut surface was tan-white, fleshy with intervening yellowish gelatinous areas. Focal small areas of hemorrhages were present [Figure 2].

Microscopy showed a variably cellular spindle cell neoplasm with hyper- and paucicellular areas. The neoplastic cells were arranged in short and long interlacing fascicles [Figure 3]a. The tumor was mitotically active with up to 30 mitoses/ 10 HPF. Foci of necrosis (approximately 20% of the tumor) and scattered inflammatory cells were identified. Additionally, areas within the tumor had heterotrophic immature osseous tissue [Figure 3]b. A battery of immunohistochemical stains were performed, which included smooth muscle actin (SMA), S100, desmin, CK (AE1/AE3), EMA, CD117, CD34, chromogranin, synaptophysin, HMB 45 and Ki-67. The tumor cells showed diffuse and strong immunoreactivity for S100 [Figure 3]-c and were negative for SMA, desmin, CK (AE1/AE3), EMA, CD117, CD34, chromogranin, synaptophysin and HMB 45. Ki-67 labeling index was 56% [Figure 3]-d. Based on the morphology and immunoprofile a diagnosis of MPNST with heterologous osteoid differentiation was offered. The patient is on close up and is doing well 5 month after the surgery.
Figure 1: CT scan showing markedly enlarged left adrenal mass displacing the left kidney and all major blood vessels. Spine shows gross kyphoscoliosis

Click here to view
Figure 2: Globular tumor with Solid fleshy cut surface with yellowish gelatinous areas

Click here to view
Figure 3: a) Tumor cells arranged in diffuse fascicle and intersecting bundles (H and E, 10). b) Tumor with areas of heterotrophic osseous differentiation (H and E, 20). c) Tumor cells are diffusely positive for S100 (40). d) Tumor shows a high MIB index. (40)

Click here to view

   Discussion Top

Von Recklinghausen's disease (neurofibromatosis-1) is an autosomal dominant disorder caused by mutation in NF-1 gene, a tumor suppressor gene, located in the chromosome 17q11.2, leading to loss of functional protein. The gene responsible for NF.1 has been cloned in the experimental mice. The proposed hypothesis included loss of heterozygosity (LOH) or homozygous mutation of NF-1 gene responsible for different sarcomas, leukemias and neural tumors. The mutation renders loss of encoding protein ''neurofibromin'' resulting in increased Ras activity and downstream MAPK/AKT signaling. There is evidence of concurrent loss of heterozygosity for NF-1 and P53 mutation in the formation of MPNST. [8] Declue et al., also demonstrated association of EFGR expression in development of MPNST. [9]

Soft tissue tumors involving the adrenal gland are relatively uncommon and primarily include various benign mesenchymal neoplasms such as hemangioma, leiomyoma, schwannoma and neurofibroma while sarcomas are extremely rare. The various malignant mesenchymal tumor of the adrenal gland are angiosarcoma, leiomyosarcoma and MPNST. MPNSTs are reported to arise either de novo or in association with neurofibroma particularly in the spectrum of Neurofibromatosis type 1. [4],[10] To the best of our knowledge only seven cases of MPNST of the adrenal gland has been reported in the literature [Table 1]. There are few cases of MPNST of the adrenal gland reported arising within a ganglioneuroma, which are considered to be induced by radiation therapy. [1] Multiple composite tumors with pheochromocytoma and MPNST with areas of heterologus element are also reported. [2],[3],[4],[5],[6]
Table 1: Summary of reported cases of adrenal MPNST

Click here to view

A meticulous and extensive sampling of the tumor along with appropriate immunohistochemistry markers and a possible ultrastructural study is required to establish diagnosis of MPNST of the adrenal gland.

A neoplasm with spindle cell morphology, dense cellularity, high mitosis and zones of necrosis hints toward high grade sarcoma. Immunohistochemical studies with a panel of antibodies are useful to discriminate different spindle cell malignancies, highlighting heterogenous nature in case of composite tumor. The tumor cells of MPNST are usually positive for neural markers S-100, CD56, protein gene product 9.5 (PGP 9.5). In high grade MPNST, S-100 tends to be focally positive, unlike our case. The panel of antibodies that usually used to rule out differentials are desmin, SMA (markers of myoid differentiation) CD117, CD34 (makers of gastrointestinal stromal tumor), inhibin (markers of gonadal sex-cord tumors), CK, EMA (for monophasic Synovial Sarcoma), HMB 45 (markers for Spindle cell Melanoma) and Chromogranin, Synaptophysin (Pheochromocytoma). Ducatman et al., described various heterologus elements like skeletal muscle, bone, blood vessels and glandular elements in the tumor in a series of 116 cases of MPNST. [11]

MPNST is a markedly aggressive tumor with high metastatic potential and poor prognosis. Majority of reported case developed metastasis or recurrence during follow up. PET-CT scan can be helpful for early detection of the same.

Zou et al., have described few predictive factors for development of metastasis and aggressiveness of the disease. [12] Tumor size ≥10 cm, nuclear p53 positivity and lack of S-100 immunoreactivity in tumor cells are independent prognostic factor for aggressiveness. Considering the size of the tumor, the present patient falls into high risk category.

   References Top

1.Chandrasoma P, Shibata D, Radin R, Brown LP, Koss M. Malignant peripheral nerve sheath tumor arising in adrenal gaglioneuroma in adult male homosexual. Cancer 1986;57:2022-5.  Back to cited text no. 1
2.Min KW, Clemens A, Bell J, Dick H. Malignant peripheral nerve sheath tumour and phecromocytoma: A composite tumor of the adrenal. Arch Pathol Lab Med 1988;112:266-70.  Back to cited text no. 2
3.Miettinen M, Saari A. Pheochromocytoma combined with malignant schwannoma: Unusual neoplasm of the adrenal medulla. Ultrastruct Pathol 1988;12:513-27.   Back to cited text no. 3
4.Sakaguchi N, Sano K, Ito M, Baba T, Fukuzawa M, Hotchi M. A case of Von Recklinghausen's disease with bilateral pheochromocytoma-malignant peripheral nerve sheath tumors of the adrenal and gastrointestinal autonomic nerve tumors. Am J Surg Pathol 1996;20:889-97.  Back to cited text no. 4
5.Ch'ng ES, Hoshisa Y, Iizuka N, Mori E, Ikeda JI, Yamamoto A, et al. Composite malignant pheochromocytoma with malignant peripheral nerve sheath tumor: A case with 28 years of tumor-bearing history. Histopathology 2007;51:420-2.  Back to cited text no. 5
6.Namekawa T, Utsumi T, Imamoto T, Kawamura K, Oide T, Tanaka T, et al. Composite pheochromocytoma with a malignant peripheral nerve sheath tumor: Case report and review of the literature. Asian J Surg 2012, http://dx.doi.org/10.1016/j.asjsur.2012.11.003  Back to cited text no. 6
7.Bolande RP. The neurocristopathies: A unifying concept of disease arising in neural crest maldevelopment. Hum Pathol 1974;5:409-29.  Back to cited text no. 7
8.Korf BR. Malignancy in neurofibromatosis type 1. The oncologist 2000;5:477-85.  Back to cited text no. 8
9.Declue JE, Heffelfinger S, Benvenuto G, Ling B, Li S, Rui W, et al. Epidermal growth factor receptor expression in neurofibromatosis type-1 related tumors and NF-1 animal models. J Clin Invest 2000;105:1233-41.  Back to cited text no. 9
10.Park JH, Ha SY, Cho HY. Malignant peripheral nerve sheath tumors of bilateral adrenal glands: Are they metachronus primary tumors- A case report. Korean J Pathol 2009;43:471-4.  Back to cited text no. 10
11.Ducatman BS, Scheithauer BW. Malignant peripheral nerve sheath tumors with divergent differentiation. Cancer 1984;54:1049-57.  Back to cited text no. 11
12.Zou C, Smith KD, Liu J, Lahat G, Myers S, Wang WL, et al. Clinical, pathological, and molecular variables predictive of malignant peripheral nerve sheath tumor outcome. Ann Surg. 2009;249:1014-22.  Back to cited text no. 12

Correspondence Address:
Manas R Baisakh
Consultant Pathologist, Department of Pathology, Apollo Hospital, 251, Sainik School Road, Unit - 15, Bhubaneswar - 751 005, Odisha
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.130924

Rights and Permissions


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]

This article has been cited by
1 Sonographic appearances of adrenal schwannomas
Wei Zhou,Ying Zhu,Lu Zhang,Shangyan Xu,Weiwei Zhan
Journal of Clinical Ultrasound. 2019; 47(1): 3
[Pubmed] | [DOI]
2 CT findings of adrenal schwannoma
Y.-m. Zhang,P.-f. Lei,M.-n. Chen,X.-f. Lv,Y.-h. Ling,P.-q. Cai,J.-m. Gao
Clinical Radiology. 2016; 71(5): 464
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Report
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded111    
    Comments [Add]    
    Cited by others 2    

Recommend this journal