Case Reports

Castleman_s Disease of the Rectum: Report of a Case Taishi Hata, M.D., Ph.D.,1 Masataka Ikeda, M.D., Ph.D.,1 Masakazu Ikenaga, M.D., Ph.D.,2 Masayoshi Yasui, M.D.,1 Tatsushi Shingai, M.D.,1 Hirofumi Yamamoto, M.D., Ph.D.,1 Masayuki Ohue, M.D., Ph.D.,1 Mitsugu Sekimoto, M.D., Ph.D.,1 Yoshihiko Hoshida, M.D., Ph.D.,3 Katsuyuki Aozasa, M.D., Ph.D.,3 Morito Monden, M.D., Ph.D.1 1 2 3

Department of Surgery and Clinical Oncology, Osaka University, Osaka, Japan Department of Surgery, Osaka National Hospital, Osaka, Japan Department of Pathology, Graduate School of Medicine, Osaka University, Osaka, Japan

ABSTRACT: Gastrointestinal Castleman_s disease is very rare. We report the case of a 52-year-old patient with asymptomatic rectal polyp, which was diagnosed as Castleman_s disease. The rectal polyp was identified during preoperative workup of gastric adenocarcinoma. The rectal polyp was 4-cm long with a short, thick stalk. Pathologic examination of the resected polyp showed lymph follicle hyperplasia with remarkable lymphocyte and plasma cell infiltration in the submucosal area, consistent with plasma cell type of Castleman_s disease. This is the first report of Castleman_s disease of the rectum concomitant with gastric adenocarcinoma. A literature review of Castleman_s disease identified only five cases of gastrointestinal Castleman_s disease, and all five cases were of the hyaline vascular type. A high index of suspicion of this disease is important for preoperative diagnosis. [Key words: Castleman_s disease of the rectum; Plasma cell type; Polypoid shape]

the lymph follicle, multiple blood vessel penetration, and infiltration of plasma cells in the interfollicular area. In 1972, Keller et al.3 named this disease Castleman_s disease and divided 81 cases into two types: hyaline vascular (HV) type, and plasma cell (PC) type, and this classification is still used at present. Furthermore, they reported that this disease also can be found in the neck and abdominal cavity. Since then, Castleman_s disease has been given different names, such as angiofollicular lymph node hyperplasia and angiomatous lymphoid hamartoma.1,4–6 Several reports have described the incidence, pathogenesis, and clinical features of Castleman_s disease. However, as far as we know, Castleman_s disease of the rectum has not been reported. We report a rare form of this disease with a literature review.

n 1954, Castleman1 reported a single case of mediastinal lymphadenopathy, resembling thymoma, and subsequently reported 13 other cases with localized mediastinal lymph node hyperplasia, resembling thymoma as a disease entity.2 The pathologic characteristic of this disease is hyperplasia of

I

REPORT OF A CASE A 52-year-old male, with a past history of massive burn at age 27 years, visited the family physician with complaints of epigastric discomfort and tarry stool. Gastrointestinal endoscopy revealed advanced gastric carcinoma, and he was referred to our hospital for surgical intervention. Biopsy samples taken from the gastric lesion showed moderately differentiated adenocarcinoma. As part of general gastrointestinal checkup, digital rectal examination was performed,

Presented at the meeting of the Japan Surgical Association, Tokyo, Japan, November 13 to 15, 2002. Correspondence to: Masataka Ikeda, M.D., Ph.D., Department of Surgery and Clinical Oncology (E2), Graduate School of Medicine, Osaka University, 2-2 Yamadaoka Suita, Osaka, 565-0871, Japan, e-mail: [email protected] Dis Colon Rectum 2006; 50: 389–394 DOI: 10.1007/s10350-006-0783-z * The American Society of Colon and Rectal Surgeons Published online: 14 December 2006

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Figure 1. Pelvic CT of protruding mass in the left wall of rectum (arrow).

which identified an approximately 4-cm-long mass in the left wall of the rectum, 10 cm from the anal verge. Abdominal CT and barium enema showed a protruding mass in the left wall of the rectum (Figs. 1 and 2). The rectal mass was slightly enhanced with a contrast medium (Fig. 1). Colonoscopic examination revealed polypoid lesion with a short, thick stalk and bleeding tendency, which occupied approximately 1/2 to 1/3 of the rectal lumen (Fig. 3). Histopathologic examination of the biopsy samples taken at colonoscopy showed inflammatory changes. The patient underwent total gastrectomy with Roux-en-Y reconstruction and transanal resection of the rectal tumor. The final pathologic diagnosis of the gastric lesion based on examination of the resected speci-

Figure 3. Colonoscopic examination. The protruding mass lesion that occupied approximately 1/2 to 1/3 of the lumen had a thick stalk and large round head.

men was moderately differentiated adenocarcinoma of the stomach. Histopathologic examination of the rectal mass showed the formation of dense lymphoid tissues in the submucosal area, in which lymphoid follicles with normal to hyperplastic secondary follicles were evident. In the interfollicular areas, numerous plasma cells were identified, together with Russell_s bodies. Conspicuous small hyaline vessels were found, some of which were penetrating into the secondary follicles. Onion-skin appearance, i.e., concentric layer of lymphocytes surrounding the secondary follicles also was noted (Fig. 4). These pathologic findings were compatible with PC-type Castleman_s disease. The postoperative course was uneventful and there was no recurrence during the 22 months of follow-up.

DISCUSSION

Figure 2. Barium enema. The protruding mass was located in the rectum 10 cm from the anal verge.

Castleman_s disease is characterized by cancerous growth in the lymph node tissue throughout the body. Most often the mediastinal lymph nodes are affected. As reported by Keller et al.,3 there are two main types: HV type and PC type. HV type accounts for approximately 90 percent of the cases. Most patients with HV type are asymptomatic and have a solitary lesion. Treatment is surgical resection of the primary lesion and the recurrence rate is low when the resection is complete. In contrast, PC type

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Figure 4. Pathologic examination (hematoxylin and eosin ; A20; B40; C200). Pathologic examination of the rectal tumor revealed formation of dense lymphoid tissue in the submucosal area, in which lymphoid follicles with normo- to hyperplastic secondary follicles were evident (A, B). In the interfollicular areas, plasma cells often with Russel bodies were numerous. Conspicuous small hyaline vessels were found, some of which penetrating the secondary follicles. Onion-skin appearance, i.e., concentric layer of lymphocytes surrounding the secondary follicles also were found (C).

frequently occurs in multicentric fashion and is associated with various symptoms, such as fever, splenomegaly, and leukocytosis. Furthermore, some cases of PC type are known to transform to malignant lymphoma and Kaposi_s sarcoma (KS). Lymphoma and KS have been described to occur during the course of multicentric Castleman_s disease in 18 and 13 percent of cases, respectively.7,8 Frizzera et al.9 reported that four patients (27 percent) developed malignancies among 15 patients with PC-type Castleman_s disease. Human herpesvirus 8 (HHV-8) is the etiologic agent of KS in immunocompromised patients, with or without human immunodeficiency virus (HIV) infection.10 In addition to KS, HHV-8 has been implicated in the etiology of multicentric Castleman_s disease; it

was more frequently detected in patients with HIVassociated multicentric Castleman_s disease.7 These findings suggest that HHV-8 plays a pivotal role in the pathogenesis of both KS and multicentric Castleman_s disease, especially in immunocompromised hosts. A literature review identified four cases of Castleman_s disease with gastrointestinal malignancies: two cases with colonic adenocarcinoma, one case with esophageal cancer, and one case with gastric adenocarcinoma.9,11–13 Our case was associated with advanced gastric adenocarcinoma, and the reason for the association with gastrointestinal malignancy is not well understood. However, it can be hypothesized that Castleman_s disease may occur through HHV-8 infection in patients with immune deficiency in association with malignancies, because

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the seropositivity rate of anti-HHV-8 antibodies in the general Japanese population is not low: 1.4 percent.14 Because PC-type Castleman_s disease often arises in HIV-infected patients and HHV-8 was frequently found in these patients,7 PC-type rectal Castleman_s disease might have occurred in our patient in association with the immune deficiency caused by the advanced gastric adenocarcinoma. To our knowledge, only two cases of Castleman_s disease of the gastrointestinal tract have been reported. These two cases were found in the stomach.13,15 Three other cases that were reported as gastric pseudolymphomas also could be considered as Castleman_s disease based on the reported pathologic findings.16,17 HV-type Castleman_s disease mimicking sigmoid colon was reported, but its origin was mesentery of the sigmoid colon.18 Thus, in total, five cases of Castleman_s disease of the stomach have been reported (Table 1). Our case is the first to involve the rectum. Castleman_s disease affecting the stomach manifested as large flat tumor (submucosal tumor-like lesion).13,15 In contrast, the rectal Castleman_s disease in our case comprised a large polypoid lesion with a thick stalk. This shape was different from other rectal polyps, such as hyperplastic, adenoma, and carcinoma in situ. Pathologically, all stomach lesions were of the HV type. The rectal lesion in our case was PC type, and so far the postoperative course has been uneventful.

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Previous reports showed that PC-type Castleman_s disease was mostly diagnosed by general pathology, even when identified as a solitary lymph node in the chest without symptoms. Therefore, it is extremely difficult to diagnose our case, because gastrointestinal Castleman_s disease is rare and little information is available on diagnostic imaging. With regard to the differential diagnosis based on CT findings, diminished enhanced effect by contrast media has been reported in PC type compared with HP type19; however, we detected an enhanced mass in the rectum, suggesting that there is no specific image description for this disease and that differential diagnosis is difficult. Therefore, the final diagnosis in many cases was based on the resected specimen, as was our case. In our patient, we characterized the inflammatory changes according to the histopathology of the biopsy specimen taken before operation. Obtaining a limited amount of tissue by biopsy might be the cause of misdiagnosis, but suspicion of this disease entity may be a key to a successful diagnosis. Surgical resection has been recommended in cases with a solitary lesion but not with multicentric type.3,8 After resection of the tumor, symptoms and laboratory data improved in some cases.20,21 Radiotherapy,22 chemotherapy,23 steroid therapy, and/or immunosuppressive agents have been applied in refractory cases, resulting in the improvement of clinical symptoms. However, improvement of C-reactive protein

Table 1. Summary of the Reported Gastrointestinal Castleman_s Disease Symptom (Local)

Symptom (Systemic)a

Pathologic Diagnosis

M

Epigastric pain

(+)

HV type

Subtotal gastrectomy

50

F

(+)

HV type

Stomach

58

F

(j)

HV type

Stomach

13

F

Epigastric pain Epigastric pain (j)

(+)

HV type

Stomach

66

M

(j)

(j)

HV type

Rectum

52

M

(j)

(j)

PC type

Subtotal gastrectomy Subtotal gastrectomy Mass resection Subtotal gastrectomy Mass resection

Lesion

Age (yr)

Gender

Toth and Ronay 16

Stomach

62

Toth and Ronay16 Brooks and Enterline17 Yebra et al.15 Yasuhara et al.13 Current study

Stomach

Study

Treatment

Follow-Up (mo) Death 12 mo later (other cause) Not mentioned 110 72 17 22

HV = hyaline vascular; PC = plasma cell; M = male; F = female. a Anorexia, weight loss, thrombocytosis, elevated erythrocyte sedimentation rate, anemia, hyperglobulinemia, and hyperfibrogenemia.

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and g-globulin levels has been demonstrated rarely.24 It has been reported recently the interleukin (IL)-6 is involved in the mechanism of clinical manifestation.25,26 HHV-8 encodes a gene product that is homolog of human IL-6 (vIL-6),27 and it is thought to be responsible for the clinical symptoms.28 Clinical symptoms and signs of the disease resolved and most of the abnormal laboratory values greatly improved within a few days after treatment with IL-6 antibody in patients with elevated serum IL-6 levels.29 This therapy may be useful in the future.

10. 11.

12.

13.

CONCLUSIONS We reported a rare case of Castleman_s disease of the rectum in association with gastric adenocarcinoma. It was successfully treated by tumor resection, and examination of the resected tissue showed pathologic characteristics of lymph follicle hyperplasia and marked lymphocyte and plasma cell infiltration. A high index of suspicion of this disease is important for the preoperative diagnosis, especially in patients with malignancy.

14.

15.

16.

17.

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25. Yoshizaki K, Matsuda T, Nishimoto N, et al. Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman_s disease. Blood 1989;74:1360 – 7. 26. Brandt SJ, Bodine DM, Dunbar CE, Nienhuis AW. Dysregulated interleukin 6 expression produces a syndrome resembling Castleman_s disease in mice. J Clin Invest 1990;86:592 – 9. 27. Staskus KA, Sun R, Miller G, et al. Cellular tropism and viral interleukin-6 expression distinguish human herpesvirus 8 involvement in Kaposi_s sarcoma, primary

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effusion lymphoma, and multicentric Castleman_s disease. J Virol 1999;73:4181 – 7. 28. Foussat A, Fior R, Girard T, et al. Involvement of human interleukin-6 in systemic manifestation of human herpesvirus type 8-associated multicentric Castleman_s diseases. AIDS 1999;13:150–2. 29. Beck JT, Hsu SM, Wijdenes J, et al. Brief report: alleviation of systemic manifestations of Castleman_s disease by monoclonal anti-interleukin-6 antibody. N Engl J Med 1994;330:602 – 5.