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Year : 2012  |  Volume : 55  |  Issue : 4  |  Page : 531-534
Postchemotherapy-related changes in mediastinal mixed germ cell tumor masquerading as a vascular neoplasm

1 Department of Pathology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India
2 Department of Radiology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India

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Date of Web Publication4-Mar-2013


Florid vascular proliferation in teratoma is rare morphological presentation. We present a case of mediastinal germ cell tumor masquerading as a vascular neoplasm in a 14-year-old male who presented with right hemithoracic mass. The initial histopathology of resected mass was suggestive of vascular neoplasm. Fine needle aspiration cytology (FNAC) of right axillary mass with immunohistochemistry on cell block was consistent with metastatic mixed germ cell tumor. Repeat extensive sectioning of the resected mediastinal mass showed focal viable tumor with mainly teratomatous component. Further enquiry into the history revealed patient having received prior chemotherapy; this he received in another hospital before being admitted to our hospital for surgical resection of the mass. The florid vascular proliferation may represent postchemotherapy change or a rare component of germ cell tumor possibly resistant to preoperative chemotherapy.

Keywords: Chemotherapy related changes, germ cell tumor, mediastinum, vascular proliferation

How to cite this article:
Hui M, Tandon A, Uppin SG, Paruchuri R K. Postchemotherapy-related changes in mediastinal mixed germ cell tumor masquerading as a vascular neoplasm. Indian J Pathol Microbiol 2012;55:531-4

How to cite this URL:
Hui M, Tandon A, Uppin SG, Paruchuri R K. Postchemotherapy-related changes in mediastinal mixed germ cell tumor masquerading as a vascular neoplasm. Indian J Pathol Microbiol [serial online] 2012 [cited 2020 Oct 22];55:531-4. Available from: https://www.ijpmonline.org/text.asp?2012/55/4/531/107803

   Introduction Top

Primary malignant germ cell tumors (GCTs) of the mediastinum account for 1-6% of all mediastinal tumors. [1] These tumors share similar histologic features and have a worse prognosis than their gonadal counterparts. [2] Treatment of nonseminomatous GCTs, regardless of origin, is with cisplatin-based chemotherapy regimens, followed by aggressive surgical resection of residual disease. [3] We present a case of mediastinal GCT, which was masquerading as a vascular neoplasm owing to postchemotherapy-related changes. The florid vascular proliferation mimicking a vascular neoplasm is rarely described in literature.

   Case Report Top

A 14-year-old male presented with fever, breathlessness and cough since 2 months. The contrast enhanced computed tomography (CECT) scan of chest revealed a right hemithoracic mass measuring 25 × 17 × 16 cm with collapse of right lung. Patient was subsequently referred to a higher center for further management. Open thoracotomy was done and biopsy was interpreted as hemangioendothelioma by two referral tertiary care centers. As symptoms aggravated, patient was referred to our institute. On examination, there was decreased air entry in the right lung field. Heart sounds were normal. The CECT scan of the chest was reviewed, which showed a heterogenous density mass lesion occupying the anterior mediastinum and right hemithorax suggestive of a pleuropulmonary mass. [Figure 1]a
Figure 1: (a) Nonenhanced CT reveals heterogenous density mass lesion occupying the right hemithorax, causing contralateral shift of mediastinum, abutting the heart; Postcontrast scans reveal heterogenous enhancement of the mass occupying the anterior mediastinum and hemithorax. Associated pleural effusion is also seen at the apex. (b) Cut surface of the mass is gray brown to tan brown and hemorrhagic

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The mass was excised and intraoperative findings revealed large heterogeneous vascular mass occupying whole of the right hemithorax and mediastinum extending to the right pleural cavity compressing all mediastinal structures. The mass was adherent to pericardium, right lung and pleura. The resected mass was sent for histopathological examination. On macroscopy, external surface was smooth and cut surface gray brown to tan brown, hemorrhagic and had a spongy appearance. [Figure 1]b Multiple sections examined microscopically showed multiple irregularly dilated vascular channels with tiny intraluminal papillary infoldings, organizing thrombus and areas of necrosis suggestive of low grade vascular neoplasm possibly a hemangioma. [Figure 2]a-c As no GCT component was identified and immunohistochemistry (IHC) on initial biopsy was positive for CD34, no further IHC was done. The postoperative recovery was uneventful. The patient at follow-up 1 month after surgery, presented with multiple subcutaneous swellings involving axilla, chest, and abdomen.
Figure 2: (a) Cavernous blood filled vascular spaces with intraluminal papillary projection; (b) Blood vessel showing organized thrombus; and (c) necrosis (Hematoxylin and eosin, ×100);( d; e; f; g) FNAC smears show papillary fragments and large clusters of pleomorphic cells, acinar structures, and singly scattered small cells admixed with background lymphocytes. [Figure 2d and e, Pap, ×100; 2f, Pap, ×400; 2g, MGG, × 100)

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Fine needle aspiration cytology (FNAC) of bilateral axillary lymph nodes and chest wall swellings revealed pleomorphic cells in clusters and papillary fragments suggestive of a high grade malignant neoplasm. [Figure 2]d-g The cell block sections showed cells with squamoid differentiation, few glandular structures, pleomorphic cells with vesicular nucleus along with few small to medium sized cells with hyperchromatic nuclei. The pleomorphic cells were positive for placental alkaline phosphatase and CD117. Pan cytokeratin was positive in the epithelial component. The small to medium sized cells were positive for β-human chorionic gonadotropin (β-HCG) and alpha fetoprotein (AFP). [Figure 3]a-f In correlation with immunohistochemistry, a possibility of metastatic mixed GCT was considered. As morphology of FNAC and cell block section were different from the histology of resected mediastinal mass, further clinical history and preoperative treatment details were enquired, which revealed treatment with etoposide and cyclophosphomide-based chemotherapy for 20 days in another hospital prior admission to our hospital for surgery. In view of this additional history and cytology findings, a repeat extensive sampling of resected mass was done. Most of the sections again revealed similar morphology except a focal area, which showed island of squamous cells, glands lined by tall columnar cells, immature mesenchymal areas along with smooth muscle and cartilage. Tiny foci of undifferentiated cells with hyperchromatic nuclei and scant cytoplasm were seen. [Figure 4]a-d A revised diagnosis of GCT with teratomatous component was offered. Serum tumor markers evaluated subsequently showed AFP levels of 1,21,000 IU/ml and β HCG of 10,270 mIU/ml. Hence a diagnosis of mixed GCT was considered. Patient was started on chemotherapy and discharged in stable condition.
Figure 3: (a) Cell block section show epithelial clusters, undifferentiated small to medium size cell, hemorrhagic and necrotic areas (hematoxylin and eosin, ×100). Immunohistochemistry with (b) Pancytokeratin showing strong positivity in epithelial cells(× 400); (c) CD117 positivity in few cells (× 400); (d) Placental alkaline phosphatase (PLAP) in undifferentiated small cells and pleomorphic large cells (× 400); (e) Beta HCG and f) AFP Strong positivity in undifferentiated small cells and pleomorphic large cells (× 100)

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Figure 4: Regrossed section shows focal viable teratomatous component displaying (a) squamous islands, (b) glands lined by columnar cells, (c) cartilage, (d) undifferentiated cells (hematoxylin and eosin, ×400)

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   Discussion Top

The unique feature of this case is the presence of cavernous blood filled spaces in the residual tumor mimicking vascular neoplasm. Teratomas have a disorganized structure and can be vascular but florid vascular proliferation mimicking vascular neoplasm is extremely rare. [4] Baker et al. [5] reported the presence of florid vascular proliferation in ovarian teratomas and found it to be associated with neural component of teratoma and may be confused with vascular neoplasm. Recognition of this proliferation as a benign secondary component is important to avoid misdiagnosis of a teratoma as a vascular neoplasm and possibly this phenomenon happened in our case. A thorough search of teratomatous component is warranted if there is abundant vascular proliferation mimicking vascular neoplasm especially in young patient presented with mediastinal mass.

The histological appearances of postchemotherapy residual masses may be heterogeneous with an admixture of fibrosis, necrosis, mature teratoma, and residual malignant tissue. [6] Donohue et al. presented case series of 41 patients who had surgery after chemotherapy and found that 31% had fibrosis with necrosis, 31% mature teratoma component, and 37% residual cancer. [7] Kesler et al. [3] found that the complete necrosis in the residual mass predicted excellent survival compared with mature teratoma. The present case had extensive necrosis with residual teratomatous component, which may be attributed to postchemotherapy-related changes.

Benign transformation of teratomas after chemotherapy and associated florid vascular proliferation may present a possible pitfall for the histopathologist who is unaware of the range of appearances to be found in these lesions especially if clinical details and prior treatment details are not provided. [8],[9] The present case after extensive regrossing showed necrosis with a foci of residual teratomatous component, which was missed initially due to exuberant vascular proliferation and lack of clinical and treatment details. Diagnostic clue was evident on cytology and cell block immunohistochemistry confirmed it.

Several neoplasms show vascular proliferation as component of tumor, namely, breast cancer, prostate cancer, melanoma, endometrial cancer, gliomas, and renal cell carcinoma. [10] Vascular proliferation is also seen postchemotherapy and many cancers are resistant to chemotherapy due to high vascularity. [11],[ 12] In this case prominent vasculature may be native component of GCT resistant to chemotherapy or may be secondary to chemotherapy-induced large necrosis and acute vascular injury induced by cisplatin as described in earlier reports. [13]

This case highlights the importance of keeping mixed GCT in the differential diagnosis of young patients presenting with mediastinal mass. In conclusion the finding of florid vascular proliferation mimicking vascular neoplasm is extremely rare but represents one of the intriguing features of the present case. Awareness by histopathologist of its occurrence may help to avoid misdiagnosis of a mixed GCT masquerading as a vascular neoplasm.

   Acknowledgments Top

The authors would like to acknowledge Dr. Aruna Prayaga and Dr. R.V. Kumar for their inputs.

   References Top

1.Sakurai H, Asamura H, Suzuki K, Watanabe S, Tsuchiya R. Management of primary malignant germ cell tumor of the mediastinum. Jpn J Clin Oncol 2004;34:386-92.  Back to cited text no. 1
2.Collen J, Carmichael M, Wroblewski T. Metastatic malignant teratoma arising from mediastinal nonseminomatous germ cell tumor: A case report. Mil Med 2008;173:406-9.  Back to cited text no. 2
3.Kesler KA, Rieger KM, Ganjoo KN, Sharma M, Fineberg NS, Einhorn LH, et al. Primary mediastinal nonseminomatous germ cell tumors: The influence of postchemotherapy pathology on long-term survival after surgery. J Thorac Cardiovasc Surg 1999;118:692-700.  Back to cited text no. 3
4.Akbulut M, Zekioglu O, Terek MC, Ozdemir N. Florid vascular proliferation in mature cystic teratoma of the ovary: Case report and review of the literature. Tumori 2009;95:104-7.  Back to cited text no. 4
5.Baker PM, Rosai J, Young RH. Ovarian teratomas with florid benign vascular proliferation: A distinctive finding associated with the neural component of teratomas that may be confused with a vascular neoplasm. Int J Gynecol Pathol 2002;21:16-21.  Back to cited text no. 5
6.Fizazi K, Tjulandin S, Salvioni R, Germà-Lluch JR, Bouzy J, Ragan D, et al. Viable malignant cells after primary chemotherapy for disseminated nonseminomatous germ cell tumors: Prognostic factors and role of postsurgery chemotherapy--results from an international study group. J Clin Oncol 2001;19:2647-57.  Back to cited text no. 6
7.Tait D, Peckham MJ, Hendry WF, Goldstraw P. Post-chemotherapy surgery in advanced non-seminomatous germ-cell testicular tumours: The significance of histology with particular reference to differentiated (mature) teratoma. Br J Cancer 1984;50:601-99.  Back to cited text no. 7
8.Madden M, Goldstraw P, Corrin B. Effect of chemotherapy on the histological appearances of testicular teratoma metastatic to the lung: Correlation with patient survival. J Clin Pathol 1984;37:1212-4.  Back to cited text no. 8
9.Gaudin PB, Rosai J. Florid vascular proliferation associated with neural and neuroendocrine neoplasms. A diagnostic clue and potential pitfall. Am J Surg Pathol 1995;19:642-52.  Back to cited text no. 9
10.Straume O, Chappuis PO, Salvesen HB, Halvorsen OJ, Haukaas SA, Goffin JR, et al. Prognostic importance of glomeruloid microvascular proliferation indicates an aggressive angiogenic phenotype in human cancers. Cancer Res 2002;62:6808-11.  Back to cited text no. 10
11.Glomeruloid microvascular proliferation is associated with lack of response to chemotherapy in breast cancer. Br J Cancer 2011;1059-12.  Back to cited text no. 11
12.Meirow D, Dor J, Kaufman B, Shrim A, Rabinovici J, Schiff E, et al. Cortical fibrosis and blood-vessels damage in human ovaries exposed to chemotherapy. Potential mechanisms of ovarian injury. Hum Reprod 2007;22:1626-33.  Back to cited text no. 12
13.Dieckmann KP, Struss WJ, Budde U. Evidence for acute vascular toxicity of cisplatin-based chemotherapy in patients with germ cell tumour. Anticancer Res 2011;31:4501-5.  Back to cited text no. 13

Correspondence Address:
Shantveer G Uppin
Department of Pathology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh - 500 082
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.107803

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

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