Pediatric Case Report Testicular Myeloid Sarcoma: A Rare Manifestation of Acute Myeloid Leukemia in an Infant Christine N. Tran, Angela M. B. Collie, Aron Flagg, and Audrey Rhee Myeloid sarcoma manifesting in the testis is rare and may occur concomitantly with bone marrow disease or as a separate entity. We describe our experience with a 6-month-old boy who presented with painless scrotal swelling and was found to have bilateral testicular masses on ultrasonography. The patient underwent unilateral radical inguinal orchiectomy. Surgical pathology revealed myeloid sarcoma of the testicle. He developed peripheral blood involvement 1 week postoperatively. Bone marrow biopsy showed acute myeloid leukemia. He is in remission after 2 cycles of induction chemotherapy, local radiation therapy, and allogeneic bone marrow transplantation. UROLOGY 84: 925e927, 2014.  2014 Elsevier Inc.

CASE REPORT

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he patient is a 6-month-old boy who presented for evaluation of 1 week of scrotal swelling. History was notable for prematurity (29 weeks gestation), congenital cytomegalovirus, and uneventful bilateral inguinal hernia repair at an age of 3 months. On physical examination, the patient appeared in good health. He had a normal right testicle and a distended, nonpainful, left hemiscrotum (Fig. 1A). Scrotal ultrasonography revealed an asymmetrically enlarged, hyperemic, and heterogeneous appearance of the left testis, a small left hydrocele, and fluid tracking up the left inguinal canal, thought to most likely represent orchitis or remote traumatic or ischemic pathology (Fig. 1B). The patient returned for 1 month follow-up. He progressed well in the interval. However, repeat ultrasonography was concerning for 2 new hypoechoic regions within the right testicle measuring up to 7 mm and enlargement of the previously noted heterogeneous area in the central left testicle measuring 3.1  1.6  3.2 cm (Fig. 1C,D). The patient was referred to pediatric oncology department. Labs including complete blood count and testicular tumor markers were within normal limits. The patient then underwent a left radical inguinal orchiectomy (Fig. 2A). Surgical pathology revealed myeloid sarcoma (MS) of the testicle (Fig. 2B-F). Histologic sections of the left testicle showed a diffuse mass-like infiltrate of mononuclear cells

Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Urology, The Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH; the Department of Clinical Pathology, Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, OH; and the Department of Pediatric Hematology and Oncology, Cleveland Clinic Foundation, Cleveland, OH Reprint requests: Christine N. Tran, M.D., Glickman Urological and Kidney Institute, Cleveland Clinic, Desk Q10-1, 9500 Euclid Avenue, Cleveland, OH 44195. E-mail: [email protected] Submitted: April 1, 2014, accepted (with revisions): July 1, 2014

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with round to mildly irregular nuclei, fine chromatin, and nucleoli. The cells were positive for muramidase and CD33, confirming myeloid origin, as well as CD4. They were negative for CD2, CD3, and CD34. One week postoperatively, he developed overt peripheral blood involvement and was admitted with a new diagnosis of acute myeloid leukemia (AML) for initiation of chemotherapy. Bone marrow biopsy was consistent with AML with 35% blasts and abnormal karyotype with near tetraploidy (81,XXYY,-1,-2,-3,-4,-7,-10,-11,-13,-14,-17,22[7]/46,XY[13]). He underwent 2 cycles of induction chemotherapy per protocol COG-AAML 1031 with repeat bone marrow biopsy negative for AML. Biopsies of the 2 right testicular masses were also negative for malignancy. He then underwent local radiation therapy and allogeneic bone marrow transplant and remains in remission 2 months after transplantation.

DISCUSSION MS arising in the testis is a rare clinical entity that is more commonly seen in the adult population. We present the third reported case of MS of the testis in a pediatric patient.1,2 MS is a neoplasm of myeloid blasts that involves an extramedullary anatomic site.3,4 It is referred to by multiple names in the literature including granulocytic sarcoma, monocytic sarcoma, extramedullary myeloid cell tumor, myelosarcoma, myeloblastoma, and chloroma. Any extramedullary site may be involved. Most commonly, MS arises in the soft tissues, lymph nodes, skin, and bone, with skin being the most frequently affected site.3,5,6 MS can also involve any age group, with children having a higher incidence than adults.6 Most patients with a diagnosis of MS have a history of myeloid neoplasm. MS is usually seen in patients with leukemias with prominent monocytic differentiation and is known http://dx.doi.org/10.1016/j.urology.2014.07.005 0090-4295/14

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Figure 1. (A) Left scrotal swelling on physical examination. (B) Testicular ultrasonography at 6 months showed an asymmetrically enlarged appearance of the left testis. Testicular ultrasonography at age 7 months showed (C) 2 new hypoechoic regions within the right testicle and (D) enlargement of the previously noted large hypoechoic mass in the central left testicle. (Color version available online.)

Figure 2. (A) Left radical orchiectomy gross specimen. (B) Mass-like infiltrate of mononuclear cells with residual rim of normal testicular tissue (hematoxylin and eosin; 0.4  objective). (C) Diffuse infiltrate of mononuclear cells with fine chromatin and nucleoli, consistent with myeloid blasts (hematoxylin and eosin; 20  objective). (D) The myeloid blasts are negative for CD34, which is infrequently expressed in myeloid sarcoma (20  objective). The neoplastic cells are positive for CD4 (E; 20  objective), and muramidase (F; 20  objective). The neoplastic cells are positive for (E) CD4 (20  objective) and (F) muramidase (20  objective), two markers that may be expressed in MS. (Color version available online.)

to develop in 2%-8% of patients with a history of AML.5 MS in association with AML may occur synchronously or may predate or follow the diagnosis of AML.3 In some, the presence of MS heralds leukemic conversion in a patient with myelodysplastic syndrome or an impending blast crisis in a patient with chronic myeloid leukemia.3 926

Patients rarely present with an isolated primary MS. Among the pediatric population, approximately 2%-25% of children with AML have extramedullary manifestations on presentation.7 However, in a retrospective review by Reinhardt et al,7 the incidence of AML presenting with an isolated primary MS was found to be UROLOGY 84 (4), 2014

much less common at 2.5% of AML patients. Females are slightly more likely to present with an isolated primary MS at a ratio of 1.8:1. Additionally, children with isolated MS were found to be slightly younger than the overall population of children with AML. As in adults, primary MS was also found to have a predilection for the skin. Although histologic leukemic infiltrates are common in cases of disseminated AML at autopsy, gross involvement of the testis is rare. Primary MS of the testis is even more uncommon, with only a handful of cases previously reported.3,8 MS of the testis most often presents as a testicular mass. Testicular MS has also been reported in a case of acute testicular hemorrhage in the absence of a grossly demonstrable mass.3 Other clinical findings at the time of presentation have included retroperitoneal and mediastinal lymphadenopathy, hydronephrosis, or gynecomastia in advanced cases. MS of the testis has only been previously reported in 2 pediatric patients. Armstrong et al1 described a 3-month-old boy who presented with rapid scrotal enlargement and underwent radical orchiectomy. He subsequently underwent induction therapy followed by 3 cycles of maintenance chemotherapy and remained in remission 18 months after diagnosis. Walker et al described a 2-month-old boy who presented with right scrotal swelling and ecchymosis.2 Inguinal exploration with excision of a mass arising from the anterior spermatic cord and testicular biopsy revealed MS. Bone marrow biopsy showed AML. The patient underwent chemotherapy and bone marrow transplantation and remained in remission 12 months after transplant. The histology of testicular MS is variable and may consist of a blastic proliferation of immature cells with no myeloid differentiation, poor differentiation, or welldifferentiated myeloid components.3 Histologic diagnosis of MS of the testis is challenging, especially if a history of associated myeloid disorder is lacking or if there is little or no myeloid differentiation. In fact, almost half of patients are initially misdiagnosed.9 MS of the testis is most often confused with non-Hodgkin lymphoma. However, there have also been reports of misdiagnosis as rhabdomyosarcoma or plasmacytoma.6 Management of testicular MS remains controversial but generally involves radical orchiectomy with systemic chemotherapy. Many patients also receive local radiation therapy, followed by consolidation chemotherapy or bone

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marrow transplant.6 A review by Yamauchi et al10 concluded that all cases of MS should be treated with intensive chemotherapy, even those that appear cured by resection or radiotherapy. In a series of children with MS, all children older than 6 months at diagnosis suffered local or systemic relapse if they had not received systemic therapy.7 Additionally, a delay in treatment is a real issue given the diagnostic difficulties. In children with MS, delayed or reduced treatment was found to have an adverse effect on outcomes with both increased risk for relapse and significant reduction in overall survival.7 Similar findings have been reported in the adult population.6

CONCLUSION In summary, MS of the testis should be considered in the differential diagnosis of any new solid tumor mass of the testis. MS of the testis in the pediatric population is rare, and the diagnosis may be difficult. However, appropriate histologic confirmation and prompt treatment with intensive AML-directed therapy is crucial and can lead to favorable clinical outcomes in the pediatric population. References 1. Armstrong MB, Nafiu OO, Valdez R, et al. Testicular chloroma in a nonleukemic infant. J Pediatr Hematol Oncol. 2005;27:393-396. 2. Walker BR, Cartwright PC. Granulocytic sarcoma presenting as testicular and paratesticular masses in infancy. J Urol. 2001;165:224. 3. Rawal A, Keeler TC, Milano MA. Testicular extramedullary myeloid cell tumor: report of a case wit unique clinicopathologic features and a brief review of the literature. Arch Pathol Lab Med. 2004;128:332-334. 4. Valbuena JR, Admirand JH, Lin P, et al. Myeloid sarcoma involving the testis. Am J Clin Pathol. 2005;124:445-452. 5. Constantinou J, Nitkunan T, Al-Izzi M, et al. Testicular granulocytic sarcoma, a source of diagnostic confusion. Urology. 2004;64: 807-809. 6. McIlwain L, Sokol L, Moscinski LC, et al. Acute myeloid leukemia mimicking primary testicular neoplasm. Presentation of a case with review of literature. Eur J Haematol. 2003;70:242-245. 7. Reinhardt D, Creutzig U. Isolated myelosarcoma in children—update and review. Leuk Lymphoma. 2002;43:565-574. 8. Gopal S, Marcussen S, Dobin SM, et al. Primary myeloid sarcoma of the testicle with t(15; 17). Cancer Genet Cytogenet. 2005;157: 148-150. 9. Zago LB, Ladeia AA, Etchebehere RM, et al. Testicular myeloid sarcoma: case report. Rev Bras Hematol Hemoter. 2013;35:68-70. 10. Yamauchi K, Yasuda M. Comparison in treatments of nonleukemic granulocytic sarcoma: report of two cases and a review of 72 cases in the literature. Cancer. 2002;94:1739-1746.

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Testicular myeloid sarcoma: a rare manifestation of acute myeloid leukemia in an infant.

Myeloid sarcoma manifesting in the testis is rare and may occur concomitantly with bone marrow disease or as a separate entity. We describe our experi...
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