Pelvic Castleman's disease presenting as an adnexal tumor

Abstract

Castleman's disease, first described in 1954 (1), is a rare benign disorder of unknown etiology characterized by a proliferation of lymphoid tissues. It is also known as angiofollicular lymph node hyperplasia, angiomatous lymphoid hamartoma, lymphoid hamartoma, and giant lymph node hyperplasia. Flendrig et al. (2) distinguished two basic histopathologic types and one mixed variant, which Keller et al. (3) designated the hyaline-vascular, plasma-cell, and hyaline-vascular plasma-cell types. Two clinical entities also have been described: a unicentric presentation with disease confined to a single anatomic lymph node-bearing region and a multicentric presentation characterized by generalized lymphadenopathy, systemic symptoms, hepatosplenomegaly, and a more aggressive clinical course with the potential for malignant transformation (4–6). In 70% of cases, this tumor occurs in the mediastinum (3), and the neck (7), pancreas (8), pelvis (9–13), and axillary and inguinal lymph nodes (14) are uncommon sites of involvement. In gynecologic practice, the condition appears to be extremely rare. We report a patient with unicentric Castleman's disease of the hyaline-vascular type in the pelvic retroperitoneum, which initially presented as an adnexal tumor. A 45-year-old woman, gravida 7, para 6, was referred to our hospital because of lower abdominal pain lasting for 3 days. She denied any symptoms of sweating, fatigue, or fever. Her medical and surgery history was uneventful, and her last menstrual period had occurred 2 months previous. The general physical examination was unremarkable, as were the laboratory findings, including the complete blood cell count, serum chemistry, and CA 125 level. The liver enzymes and chest X-ray were normal. The pelvic examination revealed normal external genitalia, vagina, and cervix; the uterus was of normal size and shape, mobile, and in the midposition. In the right adnexal area, an approximately 6 × 5-cm smooth, hard mass was palpable. Transvaginal sonography showed an approximately 6.3 × 4.3-cm well-defined hypoechoic mass with homogeneous components in the right pelvic cavity, which was read as a right adnexal tumor (Fig. 1). Transvaginal sonography shows an approximately 6.3 × 4.3-cm well-defined hypoechoic mass with homogeneous components in the right pelvic cavity. The patient underwent a laparotomy under the diagnosis of a right adnexal tumor. At laparotomy, the bilateral fallopian tubes and ovaries were grossly normal. The uterus was also normal in size and adherent to the anterior abdominal wall. In the right pelvic retroperitoneum, there was a well-encapsulated, rubbery firm, ovoid, and hypervascular mass located on the right internal iliac artery and separated from the uterus and right adnexa, measuring 6 × 5 × 4 cm. The upper border of this mass was just beneath the right common iliac bifurcation, the lateral border beside the right external iliac artery, the medial border in the presacral region, and the lower border pushing into the right cul-de-sac. The right ureter was pushed medially. The mass was resected with difficulty, but completely, and a frozen section was obtained. During this procedure, a large amount of bleeding from the vessels near the mass and deep right pelvic wall was experienced. The total amount of blood loss was 2200 mL. The frozen section suggested Castleman's disease of the hyaline-vascular type. On gross examination, the surface of the specimen was well circumscribed, rubbery firm, and varied from pale yellow-gray to dark reddish-brown. The cut surface appeared firm, glistening, finely granular, and pale yellow-brown in color, with some bleeding spots (Fig. 2). The microscopic examination demonstrated multiple lymphoid follicles with lymphoid cells, which were mature and showed no malignant change in an onion-skin arrangement, and ‘burn-out’ germinal centers having penetrating arterioles with hyalinized vessel walls (Fig. 3A). A rich capillary proliferation was evident in the interfollicular stroma (Fig. 3B). The capillaries were, in part, slightly hyalinized and tended to penetrate into the germinal centers. The histologic features were consistent with Castleman's disease of the hyaline-vascular type. Her postoperative course was uneventful and she was discharged 5 days after surgery. Eleven months after surgery the patient was in good health and had no evidence of recurrence. Cut surface of the specimen is firm, glistening, finely granular, and pale yellow-brown in color with some bleeding spots (→). Microscopic examination showing Castleman's disease of the hyaline-vascular type with: (A) a lymphoid follicle with lymphoid cells, which are mature and show no malignant change in an onion-skin arrangement, and ‘burn-out’ germinal centers having penetrating arterioles with hyalinized vessel walls (→) (H&E staining ×100); and (B) a rich capillary proliferation (arrowheads) evident in the interfollicular stroma (H&E staining ×40). Castleman's disease is a rare lymphoproliferative disorder. The etiology, although unclear, has been proposed to be chronic low-grade inflammation (1), with the hamartomatous process (3), an immunodeficient state (15), and autoimmunity (16,17) as likely pathogenetic mechanisms. The age of the patients reported with this entity ranges from 8 to 66 years, with no particular sex predilection. There are two major histologic types of Castleman's disease: hyaline-vascular lesions, which account for approximately 90% of the cases, and are characterized by small hyaline-vascular follicles and an interfollicular capillary proliferation; and plasma-cell lesions, which account for approximately 10% of the cases, and are characterized by large follicles with intervening sheets of plasma cells. Only an occasional mixed variant case has been reported. The majority of patients are younger than 30 years old, and those with the hyaline-vascular type are usually asymptomatic. On the other hand, systemic manifestations, such as fever, fatigue, anemia, and hyperglobulinemia, have been frequently associated with the plasma-cell type (3). Recent reports of multicentric lymph node involvement having a more aggressive, and even fatal course, have resulted in the reclassification of this disease as unicentric(localized) and multicentric Castleman's disease (4). Unicentric Castleman's disease has been described as a solitary, asymptomatic mass most commonly found in the mediastinum (70%) (3,6). Less commonly, the disease may occur in any other area of the body where lymph nodes are found: the neck, pancreas, axilla, inguinal area, and pelvis. Complete surgical resection results in excellent rates of cure in patients with the unicentric variety (3,18,19). Even with the partial excision of unresectable lesions, recurrence or progression is not expected (3). Radiotherapy at doses of 3000–4500 cGy appears to be effective in patients who are poor surgical candidates or in those with unresectable lesions (18,19). Most of the multicentric cases are of the plasma-cell type (4), with frequent involvement of the spleen and a more or less aggressive course with possible infectious complications and malignant transformation (4–6). The role of surgery in multicentric disease is limited and should not be considered a realistic treatment option. Systemic therapy, in the form of steroids or single- or multiple-drug chemotherapies, has been used with varied success, whereas the role of radiotherapy in its treatment remains unclear (18,19). Our patient had unicentric Castleman's disease of the hyaline-vascular type, with an initial presentation of an impalpable abdominal mass with lower abdominal pain, but no severe clinical signs, hepatosplenomegaly, or generalized lymphadenopathy. Other symptoms reported in association with unicentric pelvic Castleman's disease include unilateral lower pelvic pain, pelvic discomfort, and frequent urination (20). All these symptoms are caused by pressure on the surrounding organs exerted by the space-occupying mass. Unicentric Castleman's disease involving the female pelvis has been reported to occur in the retroperitoneal space adjacent to the lateral pelvic wall, usually with vascularization from the iliac vessels (9,10). The hypervascularity is frequently associated with a massive hemorrhage at excision (3,11,13). In addition, pelvic and/or retroperitoneal Castleman's disease is often accompanied by remarkable fibrous adhesion to the pelvic wall, and results in a difficult surgical excision (13,21). The present case had a large amount of bleeding from the vessels near the mass and deep right pelvic wall during the surgical procedure. Therefore, we suggest that the physician should prepare for a loss of blood, with maximal capability to return fluids and blood volume quickly and efficiently. Radiographic findings are nonspecific (22). As evidenced by the transvaginal sonography obtained in the present case, the complete characterization of pelvic masses with respect to origin can be difficult. The sonographic manifestations of the focal, homogeneous, hypoechoic mass found in our patient were compatible with those considered characteristic of lymphoma. These findings are similar to those of previous reports of Castleman's disease in other anatomic locations (7,14,22). In cases of Castleman's disease of the female pelvis, the differential diagnosis should include tubo-ovarian abscess, endometrioma, and teratoma of an ovarian origin. In addition, retroperitoneal malignancy and lymphadenopathy may serve to suggest this possibility. In conclusion, we suggest that Castleman's disease should be included in the differential diagnosis of female pelvic masses when a hypoechoic mass with homogeneous components is noted in the pelvic cavity on a sonographic examination. It is important to note that our patient did not exhibit any features or have any evidence of multicentric involvement. The gynecologist must be aware of the potential implications associated with this entity. Furthermore, we must call attention to the relationship between hypervascularity and potential excess blood loss during surgery. Complete surgical resection with tumor-free margins proved to be the best therapeutic choice in this case, and resulted in a good recovery and a satisfactory outcome.