|Year : 2017 | Volume
| Issue : 1 | Page : 55-57
A rare case of mediastinal nonseminomatous germ cell tumor with acute Megakaryocytic Leukemia
GS Chowdhary, Malav Darshan Jhala
Department of Medicine, INHS Asvini, Mumbai, Maharashtra, India
|Date of Web Publication||17-Aug-2017|
Dr Malav Darshan Jhala
206, B Wing, Serenity Heights, Off Link Road, Malad West, Mumbai - 400 064, Maharashtra
Source of Support: None, Conflict of Interest: None
The most common extragonadal site of Nonseminomatous Germ Cell Tumours is the mediastinum. These are similar to their gonadal counterparts in histology but have a poorer prognosis. The association of mediastinal germ cell tumours with blood borne malignancies has been established in many case reports. However, the association of concomitant mediastinal non seminomatous germ cell tumours with Acute Megakaryocytic Leukemia is very rare with only 26 cases reported in the last 07 Decades. These patients have a very poor prognosis with only one survivor being reported till present date. AML (M7), a rare variant of Primary AML , has been more commonly associated with non seminomatous germ cell tumours. Here, we report such a rare case of dual malignancy, Non Seminomatous Germ Cell Tumour with AML (M7) which was managed at our centre.
Keywords: Acute, leukemia, Male Mediastinal Neoplasm, Megakaryocytic
|How to cite this article:|
Chowdhary G S, Jhala MD. A rare case of mediastinal nonseminomatous germ cell tumor with acute Megakaryocytic Leukemia. J Mar Med Soc 2017;19:55-7
| Introduction|| |
The association between mediastinal germ cell tumor and hematological malignancies has been known to the medical community for more than two decades., This association was established as a clinical entity by Nichols et al. in 1990. The association is rare and has been described mostly in case reports and case series for more than 20 years.,,,,, Our extensive literature review has revealed that there are only 26 reported cases of such dual malignancies coexisting together since in 1946.
The etiology is different compared to treatment-related leukemia. Acute megakaryoblastic leukemia (AML-M7), which is rare form of primary acute myelocytic leukemia (AML), is found to be more commonly associated with primary mediastinal nonseminomatous germ cell tumors. Here, we report a case of AML-M7associated with a nonseminomatous primary mediastinal germ cell tumor whose diagnosis was a challenge.
| Case Report|| |
A 30-year-old male, serving soldier, resident of Ahmedabad and hailing from Karnataka, presented with a 1 week history of retrosternal pinpricking type of chest pain radiating to the back with acute-onset nonprogressive dyspnea on exertion (modified Medical Research Council Class II) and episodic dry cough which would aggravate on supine position. There was no history of associated fever, hemoptysis, wheezing episodes, and seasonal variation of symptoms. The patient denied history of any addictions, similar episodes in the past, or any high-risk behavior. He had no history of associated comorbid illness. His initial general and systemic evaluation was normal with a normal testicular examination. During his initial workup, he was found to have polymorph nuclear leukocytosis (total leukocyte count - 14,300/cmm) with thrombocytopenia (60,000/cmm) and marginally raised serum lactate dehydrogenase levels (234 IU/L) with his chest radiograph showing a well-defined radiopaque mass in the mediastinum to the left with a wavy outline. His contrast-enhanced computed tomography (CT) thorax showed an anterior mediastinal mass lesion (82 mm × 72 mm in axial plane with 84 mm craniocaudal extension) predominantly on the left side with lesion compressing the arch of aorta and left side main pulmonary artery and inferior pulmonary vein while a whole body positron emission tomography CT scan showed large mass lesion with heterogeneous fluorodeoxyglucose (FDG) uptake measuring 82.3 mm × 110.0 mm × 92.9 mm in the anterior mediastinum mainly on the left side with a diffusely increased FDG uptake in the bone marrow. His serum tumor markers were also elevated; alpha-fetoprotein (AFP) - 641.23 ng/ml (normal - 0–9) and beta-human chorionic gonadotropin (BHCG) - 58.9 mIU/ml (nonpregnant - 0–5). An ultrasound-guided tru-cut biopsy of his mediastinal mass showed features of a mediastinal nonseminomatous germ cell tumor likely teratoma on histopathology [Figure 1]. In view of persistent thrombocytopenia and a peripheral blood smear showing leukocytosis with blasts (high N/C ratio, sieve-like chromatin and 1–2 nucleoli) and thrombocytopenia (<10,000/cmm), [Figure 2] we performed a bone marrow aspiration and biopsy. Bone marrow studies showed focal high cellularity of large bizarre cells with a high N:C ratio, moderate cytoplasm, and convoluted to lobated nuclei with brisk mitotic activity with reduced normal hematopoietic marrow elements and no mature megakaryocytes or glands/mucin/epithelial cells, myeloperoxidase and periodic acid–Schiff's stain negative [Figure 3]. The bone marrow immunohistochemistry and flow cytometry showed CD61 positive blasts suggestive of megakaryocyte lineage with normal lymphoid and myeloid series. He was managed as a case of mediastinal germ cell tumor with AML-M7 with two cycles of BEP regimen followed by induction chemotherapy with daunorubicin and cytosine arabinoside (7 + 3 regimen). However, he developed febrile neutropenia after induction chemotherapy with progressed to septic shock with multiorgan dysfunction. He subsequently succumbed to sepsis after 45 days of diagnosis.
|Figure 1: Mediastinal biopsy: Hair shafts seen, suggestive of a teratomatous differentiation (H and E, ×40).|
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|Figure 2: Peripheral blood smear showing a blast with peripheral blebbing of the cytoplasm suggestive of a megakaryocytic lineage (Giemsa).|
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| Discussion|| |
The mediastinum is the most common site of primary extragonadal germ cell tumors. One to six percent of all mediastinal tumors are primary malignant germ cell tumors. Extragonadal germ cell tumors generally occur in the midline of the body, like the pineal gland, mediastinum, and retroperitoneum. The histological characteristics of extragonadal germ cell tumors are like their testicular counterparts but have a poorer prognosis. These tumors are closely related to serum tumor markers, especially serum AFP and BHCG levels, which aid in the diagnosis of the disease. Our case was a diagnostic challenge as the bone marrow studies were revealed features of AML-M7morphologically but had inconclusive immunohistochemistry and flow cytometry on two instances. It was only after a review of the slides was done with the intention to look specifically for megakaryocytic precursors that the tissue diagnosis was achieved. It was a tricky task to manage this patient as he had persistent thrombocytopenia requiring frequent platelet component therapy to initiate chemotherapy. He eventually developed chemotherapy-related febrile neutropenia which progressed to sepsis with septic shock, and he succumbed to his illness after nearly 10 weeks from the time of first clinical suspicion diagnosis. Our extensive review of literature of the association between nonseminomatous mediastinal germ cell tumors and AML revealed a total of 26 such cases reported since 1946. Out of these cases, 20 were males while the sex of 6 was not known. The median age of presentation with this malignancy has been found to be 23 years (15–46 years) with an average time to the diagnosis being 9 weeks (2–39 months) and a median time to death being 6 months. Out of these cases, there has been only one survivor reported who underwent allogeneic bone marrow transplant. The prognosis of these patients has been found to be poor even after timely diagnosis and initiation of treatment. The review of literature also revealed that most of the cases succumbed to chemotherapy-related complications.
| Conclusion|| |
Mediastinal nonseminomatous germ cell tumors with AML-M7 is a rare and elusive combination of dual malignancies which affects the young male population and has a poor prognosis.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
DeMent SH, Eggleston JC, Spivak JL. Association between mediastinal germ cell tumors and hematologic malignancies. Report of two cases and review of the literature. Am J Surg Pathol 1985;9:23-30.
Nichols CR, Hoffman R, Einhorn LH, Williams SD, Wheeler LA, Garnick MB. Hematologic malignancies associated with primary mediastinal germ-cell tumors. Ann Intern Med 1985;102:603-9.
Nichols CR, Roth BJ, Heerema N, Griep J, Tricot G. Hematologic neoplasia associated with primary mediastinal germ-cell tumors. N
Engl J Med 1990;322:1425-9.
Orazi A, Neiman RS, Ulbright TM, Heerema NA, John K, Nichols CR. Hematopoietic precursor cells within the yolk sac tumor component are the source of secondary hematopoietic malignancies in patients with mediastinal germ cell tumors. Cancer 1993;71:3873-81.
Menon R, Twardowski P, Forman SJ, Huang Q, Slovak ML, Krishnan A. Primary gonadal germ cell tumor associated with acute leukemia with common cytogenetics. J Clin Oncol 2010;28:e96-8.
Hartmann JT, Nichols CR, Droz JP, Horwich A, Gerl A, Fossa SD, et al.
Hematologic disorders associated with primary mediastinal nonseminomatous germ cell tumors. J Natl Cancer Inst 2000;92:54-61.
Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. 19th
ed. New York: McGraw-Hill Education; 2015.
Walsh GL, Taylor GD, Nesbitt JC, Amato RJ. Intensive chemotherapy and radical resections for primary nonseminomatous mediastinal germ cell tumors. Ann Thorac Surg 2000;69:337-43.
Wychulis AR, Payne WS, Clagett OT, Woolner LB. Surgical treatment of mediastinal tumors: A 40 year experience. J Thorac Cardiovasc Surg 1971;62:379-92.
Bajorin D, Katz A, Chan E, Geller N, Vogelzang N, Bosl GJ. Comparison of criteria for assigning germ cell tumor patients to “good risk” and “poor risk” studies. J Clin Oncol 1988;6:786-92.
[Figure 1], [Figure 2], [Figure 3]