Testicular plasmacytoma is rarely reported. The diagnosis is mainly based on pathological examination. Orchiectomy, combined with chemotherapy and radiotherapy, is currently the main treatment strategy for testicular plasmacytoma. The prognosis of extramedullary plasmacytoma involving the testis is much better than multiple myeloma involving the testis. Herein we present a case of a 62-year-old man who was diagnosed with testicular plasmacytoma.
A 62-year-old man complained of a left scrotal mass for more than 20 days. Physical examination revealed a hard, textured, non-tender mass in the left side of the scrotum, 5 cm × 2 cm × 3 cm in size, with an obscure boundary and a rough surface. However, a 5 cm × 3 cm × 2 cm cystiform mass was found within a diaphanous scrotum. The laboratory findings were normal, including routine blood tests, urine tests, biochemical markers, trophoblast hormone, alpha fetoprotein, carcinoma embryonic antigen, ferritin, CA125 and CA19-9. Ultrasonography showed that the size of the left testis was 5.1 cm × 2.4 cm × 3.2 cm. The testicular amicula had a rough surface with an irregular shape. The internal echo in the testis showed an uneven structure with clumping of low level echo densities. The maximal size was 2.3 cm × 1.4 cm. There was a rich blood supply in the testis, and the Vmax of one artery was 7.4 cm/s. In addition, there was a 5.4 cm × 3.2 cm fluid space in the vaginal cavity of the left testis. Therefore, the diagnosis was a left testiculoma with a left testicular hydrocele. A computed tomogram of the posterior peritoneum and ultrasonography of the liver, gallbladder, pancreas, spleen, kidneys, ureters, and bladder were normal. After the proper preoperative procedures, radical excision of the left testis was performed under spinal anesthesia. The pathological report showed clear surgical margins of the tumor. The microscopic examination showed that the tumor cells had abundant cytoplasm, nuclear atypia, crude chromatin, wheel-type and asymmetric nuclei, some acidophilic nucleoli, and plasmablasts (Figure 1). Tumor cell infiltration was not observed in the epididymis. Together, these results were consistent with a malignant plasmacytoma of the left testis. Immunohistochemical assay showed that CD79α and EMA were positive, but LCA, CD45RO, CD20, CD3, CD15, CD30, CD99, CD128, and placental alkaline phosphatase (PLAP) were negative (Figures 2 and 3). Postoperative serological examination showed that the levels of IgG, IgA, IgM, and complement C3 and C4 were 9.73, 2.3, 0.5, 1.27, and 0.33 g/L, respectively. Protein electrophoresis showed that the percentages of albumin, and α1, α2, β, and γ globulins were 56.5%, 4.6%, 9.3%, 13.4%, and 16.2%, respectively, and the ratio of albumin-to-globulin was 1.30. The levels of type κ and λ L-chains in serum and urine were 8.79 and 3.69 g/L, and 0.0542 and 0.05 g/L, respectively. Skull X-rays showed many scattered small-round and low-density shadows with clear boundaries, suggesting infiltration of plasmacytoma cells. There were no abnormal radiographic findings in the lumbar spine, pelvis, and cervical ribs. Bone marrow aspiration revealed 8% immature and mature plasma cells and morphologically-stained slides showed proto-plasmocytes and dikaryon plasma cells. After surgery, the patient was treated with MP formula (6 mg/d of L-sarcolysine and 60 mg/d of prednisone for 7 days) every 6 weeks for 1 year. The patient suffered from multiple osseous metastasis and died of multi-organ failure 16 months after surgery.
Testicular plasmacytoma is usually categorized as follows: (1) multiple myeloma (MM) invading testis, and (2) extramedullary plasmacytoma (EMP) originating from the testis. MM is a kind of malignant tumor of the mesenchymal tissue developed from the paraplasm of monoclonal plasmocytes. Primary MM is mainly located in the bone marrow, but neoplastic cells may generally and frequently invade other tissues and organs, such as the liver, lung, spleen, pancreas, kidney, and lymph nodes. The digestive tract, thyroid, heart, testis, ovary, and skin may also be invaded, although the testis is rarely involved. There have been 71 cases documented (4 cases in China), with only 1 case of testicular plasmacytoma complicated with a hydrocele of the testis. Anghel et al1 reported that the incidence of testis palsmacytoma accounted 0.03% of all testiculomas, and 0.6% of all MM types. EMP originates from other extramedullary tissues with a male predilection (3:1= male:female) and accounts for < 4% of malignant plasma cell tumors.2 More than 80% of EMP occurs in pate, especially the upper respiratory tract, such as the nasal cavity, pharynx, and throat-almond. However, EMP in the thyroid, liver, spleen, pancreas, digestive tract, testis, and skin are rare. The criteria for diagnosis of EMP are as follows: (1) biopsy demonstrates a single extramedullary site of the plasmacytoma, with or without involvement of lymphoid tissue, and without changes to the skeleton (which may exclude the possibility of MM); (2) bone marrow aspiration reveals < 5% plasmocytes; and (3) other parameters of the bone marrow are normal.
Cytogenetic study on testicular plasmacytoma
The genetics of MM has been well-studied in all types of malignant plasmacytomas. The abnormality of chromosomal structures and numbers are found in 20%-40% of patients with MM. Among them, polyploid and chromosome elimination are most frequent. However, other abnormities, such as chromosomal interchanges, deletions, and mutations, and the fusion of the IgH gene and oncogenes cyclin D1, cyclin D3, and fibroblast growth factor receptor 3 (FGFR3) are also reported.3 Polysomy of chromosomes 5, 7, 9, 11, 15, 19, or 21, and loss of chromosomes 8, 13, or 14 are common. The monomer deletion or escalation of chromosome 13 is found in 15%—48% of newly diagnosed patients.4 However, there are few reports on the genetics of EMP. Laso et al5 reported similar chromosome abnormalities between EMP and MM, and concluded that EMP may be manifestation of MM in its early stage.
Clinical features and diagnosis of testicular plasmacytoma
The MM patient complicated by testicular involvement might have typical clinical manifestations of MM, such as bone pain, anemia, hemorrhagic tendencies, infections, and kidney impairment. Analysis of a hemogram shows orthocyte normochromic anemia, leucocyte counts in the normal or low-normal range, and a few neoplastic cells in the peripheral blood. Bone marrow aspiration reveals more than 15% myeloma cells of the nucleated cells in the bone marrow. However, it is not easy to find neoplastic cells in the early stages of the disease. The appearance of M protein in the serum is one of the main characteristics of this disease. In addition, Bence-Jones protein is found in the urine in 50%-60% of patients with MM. A radiograph shows osteolytic lesions, diffuse osteoporosis, pathological fractures, and sclerotin hardening. Walker et al6 reported that B-scan ultrasonography of testicular plasmacytomas shows signs of gray scale ultrasound and rich blood flow, which significantly exceeds other testicular germinomas. Their results were similar to our findings in this case. EMP that develops primarily in the testis usually has no clinical manifestations. However, when complicated with other tissue or organ involvement, some clinical symptoms are observed. As described in previous reports, the primary manifestation of most testicular plasmacytomas is a testicular mass without pain.1,2,7 For example, this patient lacked typical evidence of MM in clinical manifestations, laboratory tests, and imaging findings preoperatively.
Considering the diversity and atypical clinical manifestations of plasmacytomas, the preoperative diagnosis of testicular plasmacytoma is extremely difficult. It is important to obtain a detailed history of the illness. For those patients with medical records of MM or lymphomas, when a testicular mass is observed, it usually indicates the possibility of a testicular plasmacytoma. However, confirmation of the diagnosis will depend on the pathological examination. For those patients complicated with a hydrocele, even though undetectable in some cases, preoperative cytologic examination (needle aspiration) should be considered.7
Light microscopic examination shows condensed plasma cells with diverse maturity, displaying diffused hyperplasia and infiltration. The nuclei in mature plasma cells appear round or oval with identical sizes, asymmetry, abundant cytoplasm, and mostly basophilic. Spoke-form nuclear chromatin is observed, but nucleoli and karyomitosis are seldom observed. For immature plasma cells, the nuclei are irregularly large with an increased nuclear-cytoplasmic ratio, a thickened nuclear membrane, and dispersed, non-spoke-form aligned chromatin, clear nucleoli, dicaryon, and karyokinesis are observed. In addition, acidophilic or basophilic cytoplasma is reduced. Intra-nuclear inclusions, such as Dutcher bodies or intra-cytoplasmic crystals are observed in neoplastic cells. There is relatively little interstitial substance in the tumor tissue. Immunohistochemical analysis showed L-chain limit, that is, positive κ and negative λ or negative κ and positive λ. H-chain staining showed IgG and IgM were positive, but IgA, IgD, and IgE were rarely positive. In addition, CD45, CD79α, VS38, EMA, and CD138 were usually positive, whereas CD128, CD20, and CD15 were negative (Figures 1–3).
Treatment and prognosis of testicular plasmacytoma
Regardless of the type of testicular plasmacytoma, orchiectomy of the involved testis should be performed first. The patient with MM-associated testicular damage usually needs postoperative chemotherapy with the common MP protocol. Interferon may inhibit the proliferation of plasma cells, and prolong the survival of the patient. The patient's symptom and physical signs may completely remit with allo- or auto-logous bone marrow transplantation. In addition, radiotherapy of regional pathological tissues could relieve regional bone pain effectively. With combined chemotherapy, the survival of patients with MM has been extended to >3 years. In immune typing, there is a better prognosis for IgG and IgA type MM, whereas the prognosis is worse for IgD and L-chain type MM (approximately 1 year).
Patients with EMP need follow-up after orchiectomy. If EMP involves other tissues or organs, radiotherapy should be considered first, as EMP is hypersensitive to radiotherapy. When confined lymph nodes are involved in EMP, radiotherapy should be performed in an extended field. Radioresistant or recurrent and residual foci after radiotherapy should be treated with surgery. Large regional tumors and tumors near other important organs should be ablated and followed with radiotherapy. For tumors with recurrence, metastasis, poorly differentiated, or local extension, adjuvant chemotherapy is effective after radiotherapy or surgery. The prognosis of EMP is relatively good. The 5-year survival reaches 50%-70%. The median survival after treatment is about 6–8 years. Alexiou et al2 found that 16% of EMP in 869 cases may transform into MM, and the transformation mostly develops within 2 years after the diagnosis of EMP, but some others transform after 10–30 years. Tsang et al8 reported that age was one of the important factors affecting the transformation of EMP into MM. Without the transformation of EMP into MM, survival rates in the groups ≤63 and >63 years of age are 64% and 37%, respectively. They also showed that EMP recurs easily, and the size of the tumor is an important factor responsible for its recurrence, with a 38% local control rate for tumors >5 cm and 100% for tumors <5 cm in diameter (P <0.01). Because of the transformation into MM and frequent recurrence, the patient with EMP should be followed-up long-term.
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