PRIMARY SMALL LYMPHOCYTIC TYPE B-CELL LYMPHOMA OF THE TESTIS:
A CASE REPORT
Author:
Paul Nimrod Firaza, MD
Co-Authors:
NELSON A. PATRON, MD, FPUA, FPCS
EDGARDO L. REYES, MD, FPUA, FPCS
ENRIQUE IAN S. LORENZO, MD, FPUA, FPCS
JUAN GODOFREDO R. BARDELOSA, III, MD, FPUA, FPCS
JOSE R. REYES MEMORIAL MEDICAL CENTER
MANILA, PHILIPPINES
ABSTRACT
Primary Testicular Lymphoma is a unique, rare, and aggressive extra nodal non-Hodgkin’s Lymphoma. We present a case of a sixty-five year-old man with a gradually enlarging, firm, non-tender testis found on the right hemi-scrotum. Ultrasonography showed a mildly enlarged right testis with multiple well-defined hypoechoic nodules seen. The B-HCG, LDH and AFP were within normal limits. Right radical orchiectomy was done. Grossly the testis showed a rubbery to firm, irregularly shaped, multinodular, tan-gray tissue. Histopathological findings composed of monotonous appearing lymphocytes diffusely infiltrating the stroma with small germinal centers. Individual cells appeared small, round with large nuclei, irregular indented nuclear contours and scanty cytoplasm. Immunohistochemical staining showed strongly positive LCA and CD20, and negative CD3. Patient underwent CHOP based chemotherapy and is currently being monitored for recurrence. Patient is on his 3rd year post-orchiectomy and apparently well on remission. This is the first case report of a primary small lymphocytic B-cell lymphoma of the testis using MEDLINE search.
Key words: Small Lymphocytic Lymphoma of the testis, Primary testicular lymphoma, B-cell Non-Hodgkin’s Lymphoma, Radical Orchiectomy
INTRODUCTION
Small Lymphocytic Lymphoma (SLL) accounted for 5-10% of all lymphomas. In SLL, the cancer cells were mainly in the lymph nodes and spleen. They were a slow-growing disease and are usually not curable with standard treatments. The life expectancy of patients depends on the stage and growth rate of the disease, wherein most patients live longer than 10 years. Sometimes, these slow-growing lymphomas turn into a more aggressive type of lymphoma. (1)
Primary Testicular Lymphoma (PTL) is a rare type of testicular malignancy (1-2 %), and an aggressive extra nodal non-Hodgkin’s Lymphoma (NHL) accounting for 1-9% of all testicular malignancy. It is the most common testicular tumor in males between 60 and 80 years old. (2-5) There were various subtypes, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, and follicular lymphoma. A new aggressive lymphoma subtype have been described however still unclassifiable with morphologic and genetic features intermediate between DLBCL and Burkitt lymphoma but for biologic and clinical reasons is not included in these categories. Some of the reported cases were previously classified as Burkitt-like lymphoma, T-cell, Hodgkin, lymphoblastic, and follicular lymphomas and plasmacytoma. (6–10) In adult testis, primary DLBCL was the single most frequent lymphoma (80%–90%), whereas the majority of testicular lymphomas in children represent secondary involvement by Burkitt lymphoma, DLBCL, or lymphoblastic lymphoma.(11) Most patients presented with a unilateral testicular mass or swelling and up to 90% of patients have stage I or II disease at diagnosis (60 and 30%, respectively). PTL demonstrated a continuous pattern of relapse and propensity for extra-nodal sites such as the central nervous system and contralateral testis. (12)
Primary testicular DLBCL was a very aggressive malignancy with a poor outcome. In spite of initial complete remission, most patients even with stage I/II disease experienced relapse.(13) Most relapses occured within the first 2 years of follow-up. In the largest reported series of patients, the International Extranodal Lymphoma Study Group observed 5- and 10-year overall survival rates of 48% and 27%, respectively.(14) Several variables that have been reported as prognostic factors include age, performance status, systemic symptoms, tumor burden >9 cm, spermatic cord involvement, lactate dehydrogenase serum level, histologic grade, vascular invasion, degree of sclerosis, and stage of disease.(14,15)
This study is aimed at presenting the clinicopathologic features, immunohistochemical findings and response to management of the first case of primary small lymphocytic type B-cell lymphoma of the testis as far as the knowledge of the author and through PUBMED search.
CASE REPORT
A 65 year-old male presented with a 1-year history of gradually enlarging, firm, non-tender testis. Eleven months prior to consult, patient consulted a primary physician with right scrotal pain of a numeric pain rating score of 4/10 accompanied with scrotal enlargement. Inguino-scrotal ultrasound showed enlarged testis with multiple nodular structures of varying sizes within and having measurement ranging from 0.3 cm to 2.7 cm in diameter. This was signed out as orchitis and varicocoele, right and hydrocele, left testis. Patient was given antibiotics with resolution of scrotal pain noted. Follow-up ultrasound was done after 1 month with findings of mildly enlarged right testis with multiple well-defined hypoechoic nodules two of which measures 2.4 x 2cm and 2.1 x 2.3cm with noted increased vascular flow. Several tiny calcific foci are seen with serpentine, hypoechoic, and mildly dilated veins posterior to the right testis. B-HCG was normal with results less than 0.10 mIU/ml (Normal limits: 0-5.3 mIU/ml), LDH was noted to be within normal limits 188 U/L (Normal limits: 135-225 U/L), and AFP was also normal, 3.51 (Normal limits 0-5 IU/ml). One month prior to admission, patient noted progressive enlargement of the right testis hence was admitted. Impression was Testicular New growth, right. Patient underwent Radical Orchiectomy, right. Grossly the right testis measures 11.5 x 6.5 x 6.0 cm (Figure 1). The external surface of the testis show a rubbery to firm, irregularly shaped, multinodular, tan-gray tissue with cut section showing a smooth, solid tan-brown surface with tan-white mass measuring 8.0 x 6.0cm. Microscopic section of the testis composed of monotonous appearing lymphocytes diffusely infiltrating the stroma with small germinal centers noted. Individual cells appear small, round nuclei, with irregular, indented nuclear contours, scanty cytoplasm and fine to coarsely granular chromatin (Figure 2-5). Some areas shows sheets of uniform cells divided into poorly demarcated lobules by delicate set of fibrous tissue with individual cells appearing large and round with a distinct cell membrane, clear watery appearing cytoplasm and centrally located nucleus with prominent nucleoli (Figure 6). The histopathomorphological finding was diagnosed as Small Round Cell Tumor with consideration of classic Seminoma versus Lymphoma, and immunohistochemical staining was suggested. The post-operative course was uneventful and the patient was discharged on the 1st post-operative day. Review of slides with immunohistochemical staining showed a strongly positive for neoplastic cells for LCA and CD20 and negative for CD3. Whole abdominal CT showed no enlarged lymph nodes in the retroperitoneal, iliac and inguinal regions. No osteolytic lesions seen. Patient then underwent Cyclophosphamide 1087.5mg, Hydroxydaunorubicin 72.5, Oncovin 2mg, Prednisone 30mg BID treatment computed at 1.45 B.S.A. Patient completed his 6 cycles and was monitored for recurrence thereafter. During his 1st year post treatment, patient had community-acquired pneumonia with complications of pleural effusion. Patient then underwent, chest tube thoracostomy with cytology report showing negative for malignancy. Patient is on his 3rd year post-orchiectomy and apparently well on remission.
DISCUSSION
This is the first case of primary testicular lymphoma of small lymphocytic type reported in literature. There are no case report found using a MEDLINE/PUBMED search performed with keywords like primary testicular lymphoma and small lymphocytic type, small lymphocytic lymphoma and testis with additional filters applied for human studies.
We are presented here with a 65-year-old male with a one-year history of a progressively enlarging firm, non-tender, non-erythematous right testicular mass with normal serum markers (B-HCG, LDH and AFP) and histologic findings composed of monotonous appearing lymphocytes diffusely infiltrating the stroma with small germinal centers and individual cells appear small, round with large nuclei, irregular indented nuclear contours and scanty cytoplasm. Confronted with a case of a firm intratesticular mass, cancer should be considered until proven otherwise. It which would comprise of a morphologically and clinically diverse group of tumors, 95% of which are germ cell tumors (GCTs), 5-10% are stromal tumors and others are rare. Germ cell tumors are relatively rare malignancies, accounting for 1% to 2% of cancers among men in the US with three age model peaks: infancy, ages 30 to 34 years and approximately age 60. Syncronous bilateral testicular lymphoma is less common than GCT but accounts for the majority of testicular tumors in men older than 50 years of age. Our patient presented with a classical painless testicular mass however, presented with a unilateral primary lymphoma and also did not present any of the four well-established risk factors for testicular cancer mentioned in literature namely cryptorchidism, family history of testicular cancer, a personal history of testicular cancer and intratubular germ cell neoplasia (ITGCN).
Primary testicular lymphoma patients have a better overall prognosis as compared with nodal lymphoma but are at higher risk of late disease-related deaths. The introduction of rituximab in clinical practice does not seem to improve their early outcome.(16) In a study of Wang et al. there are three independent predictors of worse overall survival for primary testicular lymphoma namely poor ECOG performance status (PS, ≥2), infiltration of adjacent tissues (spermatic cord, epididymis, or scrotum), and bulky disease (tumor mass, >9 cm). According to these three factors, Rituximab was found to significantly prolong progression-free survival (PFS) in the low-risk group (P = 0.044) but not in the high-risk group (P = 0.748). And the combination therapy for CNS prophylaxis significantly prolonged the survival in the high-risk group (P = 0.005 for OS; P = 0.004 for PFS), but not in the low-risk group (P = 0.092 for OS; P = 0.191 for PFS). The addition of rituximab is more important for the patients without the prognostics factors, and the combination CNS prophylaxis is more significant for the patients with the prognostics factors.(17)
In men presenting with a testicular mass and hydrocele, scrotal ultrasonography is an inexpensive, noninvasive and widely available tool that should be considered. The typical GCT is hypoechoic and two or more discrete lesions may be identified while a NSGCT has heterogeneous echotexture within a lesion. The presence of increased flow within the lesion on color Doppler ultrasonography is suggestive of malignancy, which is consistent with our patient. The risk of malignancy increases with the size of the lesion. The main radiological techniques for testicular lymphomas are Doppler ultrasound for the study of the primary disease and Multidetector Computed Tomography (MDCT) in the evaluation of disease extension.(18)
One of the few malignancies associated with accurate serum tumor markers such as lactate dehydrogenase (LDH), alpha-feto-protein (AFP) and human chorionic gonadotrophin (HCG) is testicular cancer. These are considered essential for its diagnosis, prognosis, treatment, and monitoring. Serum tumor markers should be obtained at diagnosis, after orchiectomy, to monitor for response to chemotherapy, and to monitor for relapse in patients on surveillance and after completion of therapy. The normal serum marker results for our patient does not rule out GCT hence were not used to guide decision making to perform radical orchiectomy.
The histopathomorphological and immunohistochemical staining findings post-radical orchiectomy of the right testis was B-cell lymphoma, small lymphocytic type. Orchiectomy is the established diagnostic and first therapeutic procedure in cases of primary testicular lymphoma. The choice of further treatment is still controversial because of the rare incidence of the disease and lack of prospective, randomized series. Primary testicular lymphoma (PTL) has poor prognosis with failures in contralateral testis, CNS, and extranodal sites hence an international phase II trial (International Extranodal Lymphoma Study Group 10 [IELSG-10]) was conducted to address the feasibility and activity of conventional chemoimmunotherapy associated with CNS prophylaxis and contralateral testis irradiation. This international prospective trial shows that combined treatment with six to eight courses of rituximab added to cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days (R-CHOP21); four doses of intrathecal methotrexate (IT-MTX) and radiotherapy (RT) to the contralateral testis (30 Gy) for all patients and to regional lymph nodes (30 to 36 Gy) for stage II disease was associated with a good outcome. Radiotherapy avoided contralateral testis relapses, but CNS prophylaxis deserves further investigation.(12-15)
CONCLUSION
This is the first case report of a primary small lymphocytic B-cell lymphoma of the testis using MEDLINE/PUBMED search. The prognosis of this rare malignancy was poor in earlier series, however, in the advent of chemotherapy and radiotherapy later series showed promising results. This type of PTL may be classified among those with better prognosis and responsive to current treatment. However, monitoring is still of importance because even with initial complete remission of stage I/II disease relapse do occur.
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Appendices
Figure 1. Gross specimen of the right testicular mass
Figure 2. Photomicrograph of the testis composed of monotonous appearing lymphocytes diffusely infiltrating the stroma with small germinal centers noted. (Haematoxylin Eosin stain, original magnification x 40)
Figure 3. Photomicrograph of the germinal center found in the testis (Haematoxylin Eosin stain, original magnification x 400)
Figure 4. Photomicrograph of the testis with individual cells appears small, round nuclei, irregular, indented nuclear contours and scanty cytoplasm (arrow). The chromatin is fine to coarsely granular. (Haematoxylin Eosin stain, original magnification x 200)
Figure 5. Photomicrograph of the transition between normal appearing testes to a testes composed of monotonous appearing lymphocytes diffusely infiltrating the stroma with small germinal centers noted (arrow). (Haematoxylin Eosin stain, original magnification x 100)
Figure 6. Photomicrograph of testes with some areas showing sheets of uniform cells divided into poorly demarcated lobules by delicate set of fibrous tissue. The cells appear large and round with a distinct cell membrane, clear watery appearing cytoplasm and centrally located nucleus with prominent nucleoli. (Haematoxylin Eosin stain, original magnification x 200)
Figure 7. Photomicrograph of CD3 staining (original magnification x 400)
Figure 8. Photomicrograph of CD20 staining (original magnification x 400)
Figure 9. Photomicrograph of LCA staining (original magnification x 400)