Extramedullary plasmacytoma involving the penis is extremely rare. Here, we describe a case of primary extramedullary plasmacytoma of the penis in a 64-year-old man who presented with a palpable penile mass. Nuclear magnetic resonance imaging revealed the presence of a large, round non-encapsulated mass in the perineum. A contrast-enhanced computed tomography scan of the pelvis showed that the mass was located in the tunica albuginea and corpora cavernosa at the base of the penis. The mass encased the urethra and demonstrated no marked enhancement during the arterial phase. The patient underwent successful surgical resection of the tumor. Histologically, the tumor was composed primarily of neoplastic plasma cells that were positive for CD38, vimentin and Ki 67. Postoperatively, the patient recovered well and exhibited no evidence of development of multiple myeloma, local recurrence or distant metastasis at 2 months post-surgery. To the best of our knowledge, our case represents the first documented case of human primary extramedullary plasmacytoma of the penis.
Solitary plasmacytoma is a rare plasma-cell neoplasm that can be classified into two groups based on its location. These include solitary plasmacytoma of the bone, in which tumor cells are found only in the bone, and extramedullary plasmacytoma (EMP), in which tumor cells develop in tissues other than the bone (1). EMP is uncommon and accounts for <5% of all plasma-cell neoplasms (2). Most EMPs (nearly 90%) occur in the head and neck area, with a predilection for the upper respiratory tract (3). Infrequent sites of involvement include the gastrointestinal tract, lung, bladder, liver, spleen, pancreas and other organs such as breast, testis or skin (3). EMP involving the penis is extremely rare. Herein, we report a case of primary EMP arising from the penis.
A 64-year-old man was admitted due to a 3-month history of a painless mass at the base of the penis. He did not experience difficult, frequent, urgent or painful urination, or urethral bleeding. The mass was discovered incidentally 3 months ago. He denied a family history of cancer and genetic disease or any history of smoking, alcohol consumption or occupational disease. On physical examination, a round mass, ∼5.0 cm in diameter, was palpable at the base of the corpora cavernosa on the right side (Fig. 1A). The mass was hard, non-tender and mobile. No discharge came out following squeezing the mass. The mass moved along with the penis and showed no apparent association with the skin or pelvis.
Laboratory tests revealed that the patient's red blood cell count, white blood cell count and platelet count were all normal. His serum electrolyte levels were normal, and his plasma C-reaction protein level was 3.66 mg/l (normal range, 0.00–8.00 mg/l). Tumor marker tests showed that serum ferritin was slightly increased to 331.8 ng/ml (normal range, 12.0–245.0 ng/l) and his β2 microglobulin level was 1534.2 µg/l (normal range, 900.0–2300.0 µg/l).
Magnetic resonance imaging (MRI) was subsequently performed, which revealed a large round non-encapsulated mass in the perineum. The boundary between the mass and the corpora cavernosa was obscure. A contrast-enhanced computed tomography (CT) scan of the pelvis showed that the mass, measuring 6.5 cm × 5.4 cm × 5.2 cm, was located in the tunica albuginea and corpora cavernosa at the base of the penis and encased the urethra (Fig. 2A). The mass demonstrated no marked enhancement during the arterial phase (Fig. 2B) and showed no evidence of aggressive growth. There were no swollen groin lymph nodes. Based on the clinical and imaging findings, a benign tumor was initially diagnosed.
A biopsy of the mass was suggested, but the patient refused and strongly urged immediate surgery. One week later, he underwent surgical resection of the tumor. A transverse scrotal incision was made. A tumor located at the base of bilateral corpora cavernosa was seen adhered to the tunica albuginea and corpora cavernosa, with a clear boundary within surrounding tissue. The tumor was peeled off and resected by severing bilateral corpora cavernosa (Fig. 1B). After tumor resection, anastomoses of the severed bilateral corpora cavernosa and blood vessels were performed. No damage to the urethra or cavernous urethra was caused intraoperatively.
Tumor specimens were subjected to pathological examination. The tumor was composed of sheets of plasma cells at different stages of maturity (Fig. 3A). Immunohistochemistry staining of the mass indicated that the cells were positive for vimentin, Ki 67, CD38 and CD45 (Fig. 3B–D), but negative for CD138, CK, S-100, κ light chain, λ light chain, CD20, PAX-5, CD3, Mum-1, desmin and myogenin (data not shown). These features were suggestive of a primary EMP of the penis.
Postoperatively, the blood supply to the penis was good. The postoperative radionuclide bone scan was normal. A cytomorphologic examination of the bone marrow revealed no abnormalities, and the percentage of plasma cells was 3.5%. On postoperative day 2, the urinary catheter was removed and the patient voided smoothly. He was discharged on postoperative day 6. At 2 months after surgery, he exhibited no evidence of the development of multiple myeloma, local recurrence or distant metastasis.
Tumors of the penis are rare, and malignant penile tumors are even more unusual. The annual incidence of penile cancer is ∼1 in 100 000 men in Western countries (4). EMP of the penis is an extremely rare condition and, to date, there have been only two reported cases of EMP involving the penis; one was cutaneous plasmacytoma (5), while the other was penile EMP in a dog (6). Our case represents, to the best of our knowledge, the first documented case of human primary EMP of the penis.
In contrast to the previously described case of cutaneous plasmacytoma occurring in the penis (5), the tumor in our case did not affect the penile skin. The preoperative physical examination did not find a significant association between the tumor and penile skin. The CT scan revealed that the tumor affected only the tunica albuginea and corpora cavernosa. In agreement, intraoperatively, the tumor was easily peeled off and showed no significant association with the skin. Apparently, these findings suggest that the tumor in our case was not a cutaneous plasmacytoma affecting the penis, but a primary EMP of the penis.
The etiology of EMP is poorly understood, although chronic infection, chronic stimulation by irritants and a history of chronic inflammation are possible factors (7). However, these etiological factors were not identified in the present case. Clinically, most EMP patients present with a painful lesion, but some, as in our case, are asymptomatic (3). EMPs are difficult to diagnose based on clinical symptoms and signs because symptoms appear depending on the location of the tumor. CT and MRI are useful in determining the size, location and extent of the solitary lesion, as well as the type and scope of treatment required (8).
The diagnostic criteria for EMPs include monoclonal plasma cell infiltration, normal skeletal survey, normal bone marrow (plasma-cell infiltration <5% of all nucleated cells), no related organ or tissue impairment and no M-protein in serum and/or urine (9). As EMPs may convert to multiple myeloma (10), the diagnosis of EMP is primarily based on histologic confirmation of a monoclonal plasma-cell infiltrate and the exclusion of a systemic myeloma (11). Immunohistochemistry is useful in helping to establish the correct diagnosis. CD38 is a marker that may help highlight plasma cells (3). Vimentin positivity suggests that tumor cells are of mesenchymal origin. In this case, immunostaining for CD20, PAX-5 and Mum-1 was negative, excluding B-cell origin. Positive staining for CD45 and negative staining for CD3 excluded T-cell origin. A neuroendocrine tumor or myogenic tumor was also excluded because of negative staining for S-100, desmin and myogenin. Collectively, our case met the majority of diagnostic criteria for EMP and showed no sign of systemic myeloma. Of note, although the majority of EMPs are positive for either κ or λ light chain, our case was negative for both light chains. This suggests that our case may represent a rare type of heavy-chain disease.
The differential diagnosis of EMP is broad and depends on the site involved. In our patient, major preoperative differential diagnoses were penile cancer and Peyronie's disease. Penile cancer was ruled out because (i) the patient had no history of phimosis, (ii) there were no typical manifestations of exophytic penile cancer, (iii) the tumor was freely mobile and showed no aggressive growth and (iv) the tumor exhibited no significant contrast enhancement in the arterial phase. Peyronie's disease is a disorder of the penile connective tissue, which is characterized by the development of a lump on the shaft of the penis (12). It always causes curvature of the penis and, in some cases, pain. These were not observed in our case. In addition, Peyronie's disease has a relatively long natural course that usually lasts for 6–18 months (12). In contrast, the course of the disease in our patient was only 3 months.
EMPs are highly sensitive to radiotherapy, and thus local disease control and long-term disease-free survival can be achieved with radiotherapy alone (9). Treatment fields should be designed to encompass the primary tumor with a margin of at least 2 cm. The optimal radiation dose recommended is in the range of 40–50 Gy in 4.5–5 weeks, and irradiation of involved lymph nodes should be included (9). Although a surgery is not routinely recommended for the treatment of tumors occurring in the head and neck region due to its invasiveness, complete surgical resection is not inferior to radiotherapy and should be considered for patients with EMPs in other areas (9,13). Alexiou et al. (14) found that there was no significant difference in survival outcomes among patients treated with radiotherapy, surgery and radiotherapy plus surgery for EMPs occurring in areas other than the upper aerodigestive tract. However, patients with inadequate surgical margins should receive adjuvant radiotherapy (14). In patients with disseminated disease, chemotherapy should be considered (15). In our case, since the tumor was localized and there was no lymph node involvement, the patient underwent surgery without radiotherapy.
The prognosis of EMPs is good. The 10-year disease-free and overall survival rates are 50–80% in most series, while local recurrence develops in <10% of patients (3). However, 17–33% of EMP patients develop multiple myeloma, which necessitates long-term follow-up (15). The prognosis may depend on the tumor size (>5 cm) and nodal involvement. Although our patient showed no evidence of the development of multiple myeloma at 2 months post-surgery, he should be constantly monitored in view of a relatively high incidence of progression to multiple myeloma and the development of a large tumor in a relatively short period.
In conclusion, we herein document a rare case of primary EMP occurring in the corpora cavernosa. Because of its extreme rarity, awareness of this condition should be raised. The histologic confirmation of a monoclonal plasma cell infiltrate and the exclusion of a systemic myeloma are essential for a correct and definitive diagnosis. Although radiotherapy is the preferred treatment for EMP, good results can also be achieved by a complete tumor resection.
Conflict of interest statement