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  Table of Contents  
Year : 2021  |  Volume : 58  |  Issue : 1  |  Page : 131-132

Therapy-related acute promyelocytic leukemia in a patient with testicular mixed germ cell tumor

1 Department of Pathology, Government Medical College and hospital, Chandigarh, India
2 Department of Surgery, Government Medical College and hospital, Chandigarh, India
3 Department of Radiation Oncology, Government Medical College and hospital, Chandigarh, India

Date of Submission26-Sep-2019
Date of Decision17-May-2020
Date of Acceptance26-May-2020
Date of Web Publication14-Sep-2020

Correspondence Address:
Ranjeev Bhagat
Department of Pathology, Government Medical College and hospital, Chandigarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_853_19

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How to cite this article:
Kaur M, Bhagat R, Gupta S, Dimri K. Therapy-related acute promyelocytic leukemia in a patient with testicular mixed germ cell tumor. Indian J Cancer 2021;58:131-2

How to cite this URL:
Kaur M, Bhagat R, Gupta S, Dimri K. Therapy-related acute promyelocytic leukemia in a patient with testicular mixed germ cell tumor. Indian J Cancer [serial online] 2021 [cited 2021 Apr 16];58:131-2. Available from:

A 30-year-old man presented in 2016 with a swelling in the left scrotal region for 2 months. Contrast-enhanced computed tomography (CECT) revealed a heterogeneously enhancing mass measuring 7.7 × 9.1 × 8.7 cm in the left testis. A necrotic paraaortic lymph node measuring 2.2 × 2 cm was identified at the level of L1 vertebra. Both lung fields were unremarkable. No lytic or sclerotic lesion was seen in the visualized bones. Serum tumor markers were elevated; ß-Human chorionic gonadotropin-172.45 mIU/mL (reference range=0-5 IU/L), alpha fetoprotein-942.25 ng/mL (reference range=0-10 μg/L), and lactate dehydrogenase-360 U/L (reference range=140-260U/L). With a clinical diagnosis of malignant testicular tumor, left high inguinal orchidectomy was performed. On gross examination, a large gray-white to gray-brown testicular tumor distorting testicular contour with areas of necrosis and cystic degeneration was seen. Microscopic examination showed predominantly teratomatous component, other components being embryonal carcinoma with large, bizarre tumor cells having prominent nucleoli, a third component of yolk sac tumor having cells arranged in microcystic pattern, and a small component of choriocarcinoma [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. A final diagnosis of mixed germ cell tumor (GCT), stage IIB (pT2N2M0S1) was made and the patient was started on chemotherapeutic regimen comprising cisplatin (20 mg/m2, day 1 to day 5), etoposide (100 mg/m2, day 1 to day 5), and bleomycin (30 units intravenously on day 1, 8, and 15) for four cycles. Post-chemotherapy CECT done in 2017 showed no evidence of locoregional recurrence and tumor markers within normal limits. The patient was doing well till early 2019 when he presented with fever, fatigue, and pancytopenia. Bone marrow examination showed hypercellular marrow with 93% abnormal promyelocytes containing numerous Auer rods and faggot cells [Figure 1]e and [Figure 1]f. Reverse transcriptase-polymerase chain reaction (RT-PCR) was positive for PML-RARα gene fusion. Cytogenetic analysis showed t(15;17) and was negative for -5/del (5q), -7/del (7q), del (20q), and trisomy 8. A diagnosis of therapy-related acute promyelocytic leukemia (t-APML) was finally rendered. The patient was stratified as low-risk APML and started on all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) (ATRA plus ATO)-based induction and consolidation therapy. Patient has been doing well with quantitative RT-PCR negative for PML- Retinoic Acid Receptor-α (RARA) at a follow-up period of 4 months.
Figure 1: Photomicrographs showing components of mixed germ cell tumor of testis: (a) embryonal carcinoma, (b) yolk sac tumor, (c) teratoma, and (d) choriocarcinoma (H&E, ×100) (e) Bone marrow aspirate showing hypercellular marrow with abnormal promyelocytes (May Grünwald Giemsa (MGG), ×200), exhibiting numerous Auer rods (inset, MGG, ×400). (f) Myeloperoxidase cytochemical stain showing strong cytoplasmic positivity in abnormal promyelocytes (×1000)

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  Discussion Top

The current management of testicular mixed GCT is based on a combination of surgery and chemotherapy with high cure rates. However, there is also an increased risk of developing secondary malignancies. Chemotherapy with platinum based-drugs and topoisomerase inhibitors, especially etoposide in large cumulative doses, is implicated in increased risk of development of leukemia by 20–300 fold.[1] In a study of 171 patients with GCTs, Inoue et al.[2] found that four patients (2.3%) developed therapy-related acute myeloid leukemia and myelodysplastic syndrome. Out of etoposide, ifosfamide, cisplatin, and nedaplatin used for the treatment of testicular cancer, only etoposide was shown to have a significant relation between a cumulative dose and leukemogenesis.[2]

Therapy-related myeloid neoplasms (t-MN) include acute myeloid leukemia, myelodysplastic syndrome, and myelodysplastic syndrome/myeloproliferative neoplasms developing as a result of iatrogenic exposure to mutagenic agents. t-MN account for 10%–20% of all myeloid neoplasms. t-APML is an uncommon entity, the most common associated primary malignancies being those of breast, ovary, uterus, and non-Hodgkin lymphoma. In a large series of 286 cases of APML, Detourmignieset al. found that only 5.6% cases occurred due to prior cytotoxic therapy.[3] A study comparing 51 cases of t-APML with 641 cases of de novo APML reported a higher median age and a preponderance in women in the former. However, the prognosis and response to standard therapy comprising ATRA were similar in both the groups.[4]

Our patient was treated with a chemotherapy regimen consisting of etoposide, bleomycin, and cisplatin 2 years before developing APML. The occurrence of APML following mixed GCT of testis is a rare event with only one previously published case in the literature.[5]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Bokemeyer C, Schmoll HJ, Kuczyk MA, Beyer J, Siegert W. Risk of secondary leukemia following high cumulative doses of etoposide during chemotherapy for testicular cancer. J Natl Cancer Inst 1995;87:58-60.  Back to cited text no. 1
Inoue Y, Nakamura T, Nakanishi H, Oishi M, Hongo F, Okihara K, et al. Therapy-related acute myeloid leukemia and myelodysplastic syndrome among refractory germ cell tumor patients. Int J Urol 2018;25:678-83.  Back to cited text no. 2
Detourmignies L, Castaigne S, Stoppa AM, Harousseau JL, Sadoun A, Janvier M, et al. Therapy-related acute promyelocytic leukemia: a report on 16 cases. J Clin Oncol 1992;10:1430-5.  Back to cited text no. 3
Pulsoni A, Pagano L, Lo Coco F, Avvisati G, Mele L, Di Bona E, et al. Clinicobiological features and outcome of acute promyelocytic leukemia occurring as a second tumor: The GIMEMA experience. Blood 2002;100:1972-6.  Back to cited text no. 4
Kumar TN, Krishnamani, Gandhi LV, Raghunadharao D, Sadashivudu G. Therapy- related acute promyelocytic leukemia following etoposide- based chemotherapy in non- seminomatous germ cell tumor. J Postgrad Med 2014;60:84-5.  Back to cited text no. 5
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