Daunorubicin

We report a case of testicular extramedullary myeloid cell tumor in a 37-year-old man who presented with an acute testicular hemorrhage. A pathologic examination revealed no gross tumor mass. A well-differentiated extramedullary myeloid cell tumor infiltrate was seen histologically, localized largely to the seminiferous tubules. The patient had no evidence of any past or concurrent myeloid disorders. The lack of the usual clinical features of a testicular mass and the presence of an intratubular pattern of infiltration can further compound the challenges in diagnosing this entity.

(Arch Pathol Lab Med. 2004;128:332-334)

An extramedullary myeloid cell tumor (EMCT) is a localized malignant tumor of myeloid derivation occurring at an extramedullary site.1 The entity has been referred to variably in the literature as granulocytic sarcoma, chloroma, etc. EMCTs can arise in any anatomic location but most commonly occur in soft tissues, lymph nodes, skin, and bone. Testicular involvement is described rarely in EMCTs.1-5 An incidence of 5% (3 of 61 cases) and 4% (1 of 27 cases) was found in the largest histologic1 and cytologic5 series of testicular EMCTs, respectively. Clinically, testicular EMCTs usually present as scrotal masses with grossly evident testicular tumors. Histologic diagnosis can be challenging, especially if a history of an associated myeloid disorder is lacking and if there is little or minimal myeloid differentiation. We report a case of primary testicular EMCT presenting as an acute testicular hemorrhage, with no grossly demonstrable tumor mass and a predominant intratubular pattern of infiltration. This is the first report of a testicular EMCT with these unique clinical and pathologic findings.

REPORT OF A CASE

A 37-year-old man presented to the emergency department with severe acute-onset left testicular pain. The patient denied any dysuria, urethral discharge, fever, chills, nausea, vomiting, or abdominal pain. His medical history was significant for bilateral orchidopexy as an infant and a complete excision of superficial malignant melanomas of the trunk and the supraclavicular region, 6 and 4 years earlier, respectively. A physical examination revealed mild scrotal erythema and a tender, slightly enlarged left testis. A urinalysis did not show any abnormality. The complete blood count was within normal levels, with a hemoglobin level of 15.6 g/dL, a white blood cell count of 9.4 × 10^sup 3^/µL, and a platelet count of 248 × 10^sup 3^/µL. An ultrasonogram of the scrotum showed a 4.0 × 2.2 × 1.6-cm hypoechoic mass in the left testis that was interpreted as a hematoma or a hemorrhage into a tumor (Figure 1). A computed tomography of the chest, abdomen, and pelvis did not show any tumor masses or lymphadenopathy. Serum levels of [alpha]-fetoprotein and [beta]-human chorionic gonadotrophin were normal. A left orchiectomy was performed. The pathologic examination revealed primary EMCT of the testis. A bone marrow examination performed at the time of this diagnosis showed a normal trilineage hematopoiesis with no evidence of acute leukemia or any type of myelodysplastic or myeloproliferative disorder. The patient was treated with induction chemotherapy using daunorubicin and cytarabine and with consolidation therapy with cytarabine and intrathecal methotrexate. This was followed by 2600-cGy radiation therapy to the right testis. The patient was doing well at the time of the last followup, 13 months after diagnosis, with no evidence of any new-onset hematologic disorder.

PATHOLOGIC FINDINGS

The left testis measured 6.5 × 4.5 × 2.2 cm and weighed 29.6 g. Serial sectioning showed a fresh hematoma measuring 4.0 × 2.2 × 1.4 cm involving most of the testis (Figure 2). Multiple thin sections did not show any discrete tumor nodules. The entire testis was submitted for microscopic examination. The overall testicular architecture was preserved with intact seminiferous tubules set in a hemorrhagic background. Some of the tubules showed progressive maturation to spermatozoa, while others showed a dense, largely monomorphic infiltrate of cells with convoluted nuclei and moderate amounts of eosinophilic cytoplasm (Figures 3 and 4). Occasional eosinophils were also identified. A focal extension of the infiltrate into the interstitial tissue was noted. The tumor cells demonstrated strong immunoreactivity using antibodies against myeloperoxidase and lysozyme (Figure 5), confirming the diagnosis of EMCT. The cellular infiltrate penetrated the tunica albuginea and involved the epididymis.

COMMENT

EMCTs may occur synchronously with acute myeloid leukemia, or they may either predate or follow the diagnosis of acute myeloid leukemia. Occasionally, EMCT heralds leukemic conversion in patients with myelodysplastic syndrome or an impending blast crisis in patients with chronic myeloid leukemia. Very infrequently, there is no progression to acute myeloid leukemia, and EMCT remains as an isolated tumor. Morphologically, EMCTs may be blastic proliferations of immature cells with no evidence of myeloid differentiation, be poorly differentiated with only a few cells showing some myeloid differentiation, or have well-differentiated myeloid components.2 The presence of eosinophils or eosinophilic precursors in the cellular infiltrate is an important clue to the diagnosis of EMCT.

The testis is a relatively infrequent site of involvement by EMCT, even though histologie leukemic infiltrates are common in cases with disseminated acute myeloid leukemia at autopsy. Only a few detailed reports of primary testicular EMCTs exist in the literature.^11 The clinical and pathologic features of these cases are tabulated (see Table).

The current case shows unusual and interesting features. It is remarkable for the prominent intratubular pattern of spread of the EMCT infiltrate. This intratubular localization can serve as a potential source of misdiagnosis, especially in the blastic or poorly differentiated forms of EMCT, where it can be confused with intratubular germ cell neoplasia. Additionally, this appears to be the first case of testicular EMCT presenting as an acute hemorrhage without a grossly apparent tumor. A pathophysiologic mechanism for the hemorrhage was not evident on histologie examination but may possibly have involved a direct extension of the infiltrate into a blood vessel.

In conclusion, this case highlights the need to consider EMCTs in the differential diagnosis of testicular neoplasms, even in the presence of a prominent intratubular pattern of infiltration and atypical clinical presentation. This case also emphasizes the importance of submitting the entire testis for histologie examination in the absence of a grossly evident tumor.

References

1. Neiman RS, Barcos M, Berard C, et al. Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer. 1981;48:1426-1437.

2. Traweek ST, Arber DA, Rappaport H, Brynes RK. Extramedullary myeloid cell tumors: an immunohistochemical and morphologic study of 28 cases. Am I SurgPathol. 1993:17:1011-1019.

3. Roth MJ, Medeiros LJ, Eleniotba-Johnson K, Kuchnio M, Jaffa ES, StetletStevenson M. Extramedullary myeloid cell tumors: an immunohistochemical study of 29 cases using routinely fixed and processed paraffin-embedded tissue sections. Arch Pathol Lab Med. 1995;119:790-798.

4. Meis JM, Butler JJ, Osborne BM, Manning JT. Granulocytic sarcoma in nonleukemic patients. Cancer. 1986:58:2697-2709.

5. Suh YK, Shin HJC. Fine needle aspiration biopsy of granulocytic sarcoma: a clinicopathologic study of 27 cases. Cancer. 2000:90:364-372.

6. Orlandi E, Morra E, Lazzarino M, et al. Multiple granulocytic sarcomas during complete hematologie remission of acute nonlymphoid leukemia. Acfa Hacmatol. 1989:81:41-43.

7. Toki H, Okabe K, Kimura Y, et al. Granulocytic sarcoma of the intestine as a primary manifestation nine months prior to overt acute myelogenous leukemia. lpn / Clin Oncol. 1987;1 7:79-85.

8. Kawashima H, Sakmoto W, Nishijima T, Hanada M, Mori K, Maekawa M. Granulocytic sarcoma of the testis preceding acute myeloid leukemia. Urol Int. 1988:43:310-312.

9. Economopoulos T, Alexopoulos C, Anagnostou D, Stathakis N, Constantinidou M, Papageorgiou E. Primary granulocytic sarcoma of the testis. Leukemia. 1994:8:19-20.

10. Saxena A, Saidman B, Greenwald D, Wasik MA.Testicular extramedullary myeloid cell tumor in a patient with myelodysplastic syndrome. Arch Pathol Lab Med. 1996:120:389-392.

11. Ferry JA, Srigley JR, Young RH. Granulocytic sarcoma of the testis: a report of two cases of a neoplasm prone to misinterpretation. Mod Pathot. 1997;10: 320-325.

Ajay Rawal, MD; Thomas C. Keeler, MD; Michelangelo A. Milano, MD

Accepted for publication November 6, 2003.

From the Departments of Pathology (Drs Rawal and Milano) and Urology (Dr Keeler), Evanston Northwestern Healthcare, Evanston, III.

The authors have no relevant financial interest in the products or companies described in this article.

Corresponding author: Michelangelo A. Milano, MD, Department of Pathology, Evanston Hospital, 2650 Ridge Ave, Evanston, IL 60201 (e-mail: amilano@enh.org).

Copyright College of American Pathologists Mar 2004
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