Original Articles

Clinical Nuclear Medicine. 21(8):626-628, August 1996.
KINOSHITA, TOSHIBUMI M.D. *; ISHII, KIYOSHI M.D. *; MORI, YOUKO M.D. +; NAGANUMA, HIROSHI M.D. ++

Abstract:
A case of Castleman disease in the anterior cervical region is presented. Ga-67 scintigraphy revealed moderate uptake in the thyroid region. Thyroid scintigraphy demonstrated the presence of an extrinsic thyroid tumor. Contrast-enhanced CT showed dense homogeneous enhancement within the tumor. Radionuclide tracer accumulation on gallium scintigraphy as well as dense contrast enhancement on CT scan may be characteristic of Castleman disease. Castleman disease should be considered in the differential diagnosis when increased tracer activity is noted in an anterior cervical extrathyroid tumor on Ga-67 scintigraphy.

(C) Lippincott-Raven Publishers

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E. Sprinz^*, M. Jeffman, P. Liedke, A. Putten and G. Schwartsmann

Hospital de Clinicas de Porto Alegre (HCPA), Federal University of Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2350/7, Porto Alegre, CP 90.030-003, Brazil

The use of highly active antiretroviral therapy (HAART) was associated with a dramatic improvement in the outcome of patients with human immunodeficiency virus (HIV) infection [1, 2]. In this report, we would like to describe the case of a patient with AIDS-related multicentric Castleman’s disease who has also enjoyed a long-lasting complete clinical and pathological remission following the use of HAART alone.

Castleman’s disease belongs to the group of atypical lymphoid proliferations, which are usually confused with the diagnosis of malignant lymphoma. First described in 1956, the typical patient presents with either localized mediastinal lymphadenopathy or a more aggressive form of the disease characterized by diffuse lymphadenopathy and systemic symptoms [3]. The differential diagnosis of Castleman’s disease should include malignant lymphoma, as well as other causes of lymphoma-like syndromes, such as adverse reactions to drugs, autoimmune disorders and viral or bacterial infections.

Until recently, Castleman’s disease was not considered an AIDS-related event, being managed with local surgery, irradiation and cortisteroids. Cytotoxic therapy was reserved only for highly symptomatic patients with refractory disease. Over the past years, however, a newly described AIDS-related multicentric form of Castleman’s disease (MCD) has been recognized. In this aggressive form of the disease, patients develop progressive lymphadenopathy, B symptoms and usually a fatal course [4].

Our patient was a 46 year-old HIV-positive black man who presented with dyspnea, cough, hemoptysis and severe weight loss. He had fever, bibasilar rales and widespread lymphadenopathy. The blood tests were normal, except for a hemoglobin level of 10.7 g/dl. The chest X-ray showed bilateral reticulonodular infiltrates and the computed tomography (CT) scan revealed multiple mediastinal lymph nodes (Figure 1a). The CD4 count was 54 cells/mm³ and the CD4/CD8 ratio was 0.06. A supraclavicular and submandibular lymph node biopsy confirmed MCD. The additional medical work-up ruled out malignant lymphoma, catch-scratch fever, autoimmune or infectious diseases.

Due to the aggressiveness of the disease, combination chemotherapy was offered to the patient, which he refused due to fear of infectious complications. HAART (lamivudine/zidovudine plus indinavir/ritonavir) alone was started and, surprisingly, the patient showed a rapid clinical improvement, with the disappearance of B symptoms within days. By the end of an 18-month follow-up period, the CT scan showed a complete disappearance of the mediastinal lymph nodes (Figure 1b) and a new lymph node biopsy revealed only reactive changes. The CD4 count was 135 cells/mm³ and the viral load was less than 50 copies/ml. The patient remains completely asymptomatic with no evidence of Castleman’s disease following a 24 month follow-up period on HAART alone.

Our report comes as the first in which a complete histologically-proven response for a prolonged period of follow-up is clearly documented in AIDS-related MCD with the use of HAART alone. There are other reports on the clinical outcome of AIDS-related MCD, using a variety of combined therapeutic approaches including antiviral drugs, interferon-, anti-interleukin-6 and chemotherapeutic agents along with HAART. In general, tumor responses are partial and short-lasting, sometimes at the cost of significant clinical toxicity [5–8]. It should be noted that our patient did not develop a clear neoplastic transformation of the disease into a malignant lymphoma after such a long-term follow-up period. Considering the poor treatment results and high risk of infectious complications following cytotoxic therapy in the AIDS population, we postulate that patients with AIDS-related MCD should be first managed with HAART, leaving more aggressive therapeutic approaches for patients at relapse.

REFERENCES

1. Palella FJ Jr, Delaney KM, Moorman AC et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338: 853–860.[Abstract/Free Full Text]

2. Miller V, Staszewski S, Nisius G et al. Risk of new AIDS diseases in people on triple therapy. Lancet 1999; 353: 463–464.[ISI][Medline]

3. Castleman B, Iverson L, Menendez VP. Localized mediastinal lymph-node hyperplasia resembling thymoma. Cancer 1956; 9: 822–830.[CrossRef][ISI][Medline]

4. Oksenhendler E, Duarte M, Soulier J et al. Multicentric Castleman’s disease in HIV infection: a clinical and pathological study of 20 patients. AIDS 1996; 10: 61–67.[ISI][Medline]

5. Lanzafame M, Carretta G, Trevenzoli M et al. Successful treatment of Castleman’s disease with HAART in two HIV-infected patients. J Infect Dis 2000; 40: 90–91.

6. Revuelta MP, Nord JA. Successful treatment of multicentric Castleman’s disease in a patient with human immunodeficiency virus. Clin Infect Dis 1998; 26: 527.[Medline]

7. Scott D, Cabral L, Harrington WJ Jr. Treatment of HIV-associated multicentric Castleman’s disease with oral etoposide. Am J Hematol 2001; 66: 148–150.[Medline]

8. Dupin N, Krivine A, Calvez V et al. No effect of protease inhibitor on clinical and virological evolution of Castleman’s disease in an HIV-1 infected patient. AIDS 1997; 11: 1400–1401.[Medline]

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T Y Tan, MBBS, FRCR¹, K P Pang, MBBS, FRCS², H K C Goh, MBBS, FRCS², E L H Teo, MBBS, FRCR³, B Abhilash, MBBS, FRCS⁴ and N Walford, MA MB BCHIR, FRCPATH⁵

¹ Department of Radiology, Changi General Hospital, 2 Simei Street 3, Singapore 529889, ² Department of Otolaryngology, Singapore General Hospital, Departments of ³ Diagnostic Imaging, ⁴ Otolaryngology and ⁵ Pathology, KK Women’s and Children’s Hospital, Singapore

Castleman’s disease of the neck is an uncommon benign lymphoproliferative disease that usually presents as homogeneously enhancing enlarged lymph nodes on contrast-enhanced CT scan. We described the appearance of four confirmed cases of Castleman’s disease of the neck on contrast-enhanced CT scan. Three of these presented as a solitary enhancing lymph node and the fourth case presented with multiple bilateral enhancing lymph nodes. A central non-enhancing area was present in two of the three cases that presented as a solitary node. Pathological correlation of one of these cases showed that this was due to a central fibrotic scar. One of the enhancing nodes in the fourth case with multiple and bilateral lympadenopathy also contained a central non-enhancing area. We would like to propose that if a central non-enhancing scar is observed in an enhancing lymph node in the neck on CT scan, Castleman’s disease should be considered as a possible diagnosis.

Castleman’s disease is an uncommon benign lymphoproliferative disorder that is characterized by hypervascular lymphoid hyperplasia [1, 2]. When this condition affects the neck, it usually presents as a solitary neck mass. There are several previous publications on the imaging features of Castleman’s disease of the neck and most of these are single-case reports [1–5]. We would like to describe the appearance of four confirmed cases of Castleman’s disease of the neck on post-contrast CT scan, and to suggest that a central non-enhancing scar, if present, is a useful diagnostic clue of the disease.

Four patients underwent CT scan of the neck as their first line investigation, after presenting with a neck mass. The scan parameters were: 5 mm slice thickness, angle of scan parallel to the hyoid bone, scanning from the level of the external auditory canal to the root of the neck, 20 cm field of view, 135 Kv, 200 mAs and 512 x 512 matrix. All the patients, except in case 2, were given an intravenous bolus dose of 75 ml of non-ionic iodinated contrast agent. The patient in case 2 was given a bolus dose of 50 ml. Scanning for all cases started at 60 s from the onset of contrast injection.

A 33-year-old man presented with a painless, non-tender, mobile, level II lymph node of 1 year’s duration. Endoscopy of the upper aerodigestive tract was normal. CT scan showed an enhancing (136 Hounsfield units) level II lymph node measuring 4.5 cm in the longest diameter on the left side of the neck. A low-attenuation crescentic band was observed in the centre of the mass (Figure 1). The mass was excised and histopathological evaluation revealed Castleman’s disease of the hyaline vascular type

Case 2
A 12-year-old boy presented with a 4 cm non-tender, mobile level III neck lymph node on the left side for a duration of 3 months. Nasopharyngoscopy showed a normal upper aerodigestive tract. CT scan showed a left-sided 4 cm ovoid enhancing (140 Hounsfield units) lymph node at level III. A low-attenuation stellate band was observed in the centre of the mass (Figure 2a). Histology revealed Castleman’s disease of the hyaline vascular type. The gross specimen contained a dense fibrous stroma in a stellate pattern, forming a scar in the centre of the mass (Figure 2b). This correlated very well with the low-attenuation stellate band seen on the CT scan.

Castleman’s disease is an uncommon lymphoproliferative disorder with a characteristic hypervascular lymphoid hyperplasia [1, 2]. First described by Castleman and associates in 1956 [6], it has since come with many synonyms. These include angiofollicular mediastinal lymph node hyperplasia, angiomatous lymphoid hamartoma, lymph nodal hamartoma, follicular lymphoreticuloma and benign giant lymphoma [7]. The many synonyms reflect the uncertainty over its pathogenesis, although most authors would regard Castleman’s disease as a hamartoma or an inflammatory/infective lesion [2, 8].

Histologically, the disease can be divided into two types; the hyaline vascular type and the plasma cell type. The hyaline vascular type makes up about 90% of the cases [1]. Microscopically, the hyaline vascular type is characterized by abnormal small follicles and interfollicular vascularity; consisting of a network of small capillaries with thickened, hyalinized walls radially penetrating the germinal centres from the perifollicular tissue. Follicles characterized by concentric layering of lymphocytes within germinal centres can also be seen. Large fibrotic masses surrounding vessels are often found scattered in the interfollicular areas [7]. The plasma cell type makes up about 10% of the cases [1]. It is characterized microscopically by solid sheets of plasma cells in the interfollicular area. The follicles are usually larger and the prominent interfollicular capillary network characteristic of the hyaline vascular type is usually lacking in the plasma cell type [7].

More than 50% of patients with plasma cell type of Castleman’s disease have systemic manifestations including fever, fatigue, anaemia, hyperglobulinaemia and elevated sedimentation rate. Our patient in case 4 though, did not have any constitutional symptoms. Only about 3% of patients with hyaline vascular type of Castleman’s disease exhibit these features [8]. Most patients with hyaline vascular type of disease are asymptomatic, although they can present with compressive symptoms caused by the mass lesion [1]. Castleman’s disease has no sex predilection and the age of presentation ranged from 8 years to 70 years, although the youngest patient reported was diagnosed at 6 weeks after birth [8].

Surgical excision is the treatment of choice for Castleman’s disease of the neck. There is no reported recurrence for the hyaline vascular type. However, plasma cell type requires closer follow-up after the surgical excision and systemic chemotherapy may be required [8].

Castleman’s disease is usually limited to one site, although a widespread and aggressive form involving lymphadenopathy in several sites with splenomegaly has also been described [9]. The most common site of the localized form is the mediastinum (about 70% of cases). The neck is the next most common [1, 4]. Most of the previously reported cases of Castleman’s disease of the neck were of the hyaline vascular type and these usually present as a solitary mass lesion both on clinical examination and on imaging [1–5, 8]. This was also the observation in our cases, as the patients in case 1 to 3 all presented with solitary neck masses on imaging and were all of the hyaline vascular type. The exception was in case 4 where the patient presented with multiple bilateral lymphadenopathy and the histology was of the plasma cell type. It may be that plasma cell type of Castleman’s disease of the neck has a greater tendency to present as multiple rather than solitary neck masses, although a further study with a larger number of cases would be needed before this impression could be confirmed.

Castleman’s disease of the neck on CT scan has been described as well-circumscribed homogeneous mass lesion with moderate to intense enhancement [1, 3–5, 8]; with the hyaline vascular type having a tendency to enhance more than the plasma cell type, due to the greater vascularity of the former [2, 10]. One case of Castleman’s disease of the neck presenting with ring-enhancement on CT scan has also been described [2]. Unlike pelvic disease where calcification can occur in up to 50% of the cases [10, 11], calcification in the neck disease is uncommon. On MRI of Castleman’s disease of the neck, some authors have described the presence of linear hypointense signals in a stellate or arborizing pattern especially on the T₂ weighted sequences [1, 4, 12]. They attributed these hypointense signals to perivascular lamellar fibrosis or sinus histiocytes and radial fibrosis; and suggested that these hypointense signals could be an important diagnostic clue of Castleman’s disease [1, 4, 12]. In contrast, the appearance of Castleman’s disease of the neck on CT scan has often been described as non-diagnostic [4, 8]. This is because other disease conditions like lymphoma, tuberculosis, metastatic papillary thyroid carcinoma, Kaposi’s sarcoma and Kimura’s disease can also present with enhancing lymph nodes in the neck [13]. Ota and co-authors reported on a case of hyaline vascular Castleman’s disease of the abdomen which had a central stellate fibrotic area within the mass on CT scan [14]. Similar changes have not described before in previous reports of CT appearance of Castleman’s disease of the neck. Crescentic, stellate and rounded areas of non-enhancement were observed in three of our four patients (cases 1, 2 and 4, respectively). Correlation with the gross specimen in case 2 showed that dense fibrous stroma forming a scar was responsible for the appearance, similar to what was reported in Ota’s paper. Although no correlation was made with the gross specimen in cases 1 and 4, we believe that dense fibrous scar could also be responsible for the crescentic and rounded areas of non-enhancement in these two cases, respectively. The absence of a central non-enhancing area in the intraparotid mass of case 3 could possibly be due to an absence of a dense concentration of fibrous tissue. We would therefore like to propose that the presence of a central non-enhancing scar in an enhancing lymph node in the neck on contrast-enhanced CT scan could be an important diagnostic clue of Castleman’s disease.

Received for publication August 20, 2002. Revision received May 9, 2003. Accepted for publication June 23, 2003.

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A few years later, though, she became pregnant. “When I found out, I just opened my arms to God,” said Ms. Hawkins, now 35. “I had to say thank you.”

When her son was born, on Jan. 15, 1996, at 8 pounds, 5 ounces, she knew exactly what she was going to name him: Omoiyanu Ishmael. “It means ‘the miracle child that God hears,’ ” said Ms. Hawkins, sitting up in a hospital bed and inhaling oxygen from a tank in her mother’s co-op apartment in Fort Greene, Brooklyn.

A few minutes later, her 10-year-old miracle, known as Yani, arrived home from Public School 20, the Clinton Hill School. He made a beeline for his mother, embraced her warmly and said with pride, “I got 90 on a test today.”

Ms. Hawkins beamed. “He is my little leader in training,” she said. “He is the smartest.”

Next year, she hopes he will attend Philippa Schuyler Middle School in Brooklyn, a school for the gifted and talented.

The two have lived with Ms. Hawkins’s mother, Lucille Hawkins, 61, in her complex since an electrical fire damaged their apartment on Pacific Street in Brooklyn in August 2005. The co-op has three bedrooms. Also living there is Mrs. Hawkins’s other daughter, Christianna Melissa, 19, whom she adopted at 3 years old.

Mrs. Hawkins, a retired events coordinator for a bank, was also a foster mother for 20 years and adopted a son named Omar, who died of brain cancer when he was 12.

“He died three days before my 30th birthday,” said Ms. Hawkins.

Her eyes welled up, and she wiped away the tears. She said that watching him die — and hoping to be around for her son — has made her fight that much harder to live.

Ms. Hawkins recalled when she first started chemotherapy. “That was the first time I lost my hair,” she said, rolling her eyes and laughing. “I was devastated, oh please. I was bald.”

To be fashionable, she wore fabulous wigs, Ms. Hawkins said. “My mother, she made it funny. She made it not as bad as it could be.”

Ms. Hawkins’s cancer went into remission for most of her 20s, but then returned. She has become weaker and can no longer handle chemotherapy. With care from her mother, her son and two nurses, she takes eight medications a day. She has been using the oxygen since she moved in with her mother after the fire, she said.

“That’s when I started to wear this thing all the time,” she said, lifting a tube going to her nose. “My carbon levels are increasing; my oxygen will decrease if I don’t have this.”

Sitting up in the hospital bed, she pushed a pillow under her right side to cushion an inoperable fluid mass that has grown to the size of a grapefruit. She tires quickly and rarely walks. When she goes out, she uses an old, heavy electric wheelchair.

While the nurses tend to her medical needs, Mattie Williams, a home care attendant, helps with Yani’s care. Ms. Williams’s services are provided by the Brooklyn Bureau of Community Service, one of the seven charitable agencies supported by The New York Times Neediest Cases Fund.

Ms. Williams takes Yani to the park, the library and school events and helps him with his homework. “She is phenomenal,” Ms. Hawkins said.

Ms. Williams began working with the family in the fall of 2005.

Five months later, while the apartment was being fixed, Ms. Hawkins received a past-due rent notice. She owed $455. She also owed $589.06 for an electric bill. “I did not know I still had to pay” the rent for a home that was unlivable, she said.

She was told that she was still responsible for $92 a month, her portion of the subsidized rent, she said. On her income of $558 a month in public assistance, plus $200 in food stamps and $92 in public aid for Yani, she just did not have the money.

Ms. Williams approached the bureau for help, and through the Neediest Cases Fund the outstanding bills were covered. “I am so grateful,” said Ms. Hawkins, who had worked in earlier years, primarily in retail or secretarial jobs.

She is paying the $92 a month rent to remain qualified for subsidized housing. Her apartment has been largely repaired, but she wants to live in her mother’s building and is No. 135 on the waiting list.

Her mother said, “I need to have her near me.”

“But those things we go through,” said Ms. Hawkins, taking everything in stride.

“I am just grateful that God sees fit to bless me day to day,” she said. “He allowed me to have this beautiful child. And he allows me to breathe the breath of life every day. Every day that I take in one, I am glad. But for the grace of God, that could’ve been my last breath just a minute ago.”

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Archives of Pathology & Laboratory Medicine,  Jul 2005  by Roshong-Denk, Stacie L,  Bohman, Summer L,  Booth, Robert L

The multicentric form of CD is morphologically identical to the plasma cell variant. Although this type of CD is most common in individuals infected with HIV, reports of this disease have also been described in patients who have undergone renal transplantation or received immunosuppression therapy, such as cyclosporin A.8 The multicentric form is associated with HHV-8 infection. Fever, hepatosplenomegaly, peripheral lymphadenopathy, edema, and pulmonary symptoms, as well as secondary tumors related to HHV-8 infection (eg, Kaposi sarcoma, non-Hodgkin lymphoma, or plasmablastic lymphoma) are common, especially with coexisting HIV disease.2 Like the plasma cell variant, the pathogenesis of multicentric disease stems from high levels of IL-6; however, it is virally mediated.4 Human herpesvirus 8 encodes a viral IL-6 (v-IL-6), which induces endogenous human IL-6 production.4 Multicentric disease follows an aggressive course in patients with HIV and may represent a medical emergency.2 Treatment includes chemotherapy, and the HHV-8 viral load is monitored in conjunction with chemotherapy to assess the effectiveness of treatment.

The etiology of CD is unknown. It has been hypothesized that the 2 variants may represent a continuum of the same disease, that is, the plasma cell variant evolving into the hyaline-vascular variant; however, most investigators consider the 2 variants to be distinct entities.4 Interestingly, Menke et al7 found an aberrant immunophenotypical population of mantle zone B lymphocytes in all the variants of CD.

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We report CT and MR imaging findings in a case of Castleman’s disease involving the retropharyngeal space in a middle-aged woman. On CT scans, a well-marginated, homogeneous, and densely enhancing mass was detected in the right retropharyngeal space. The mass was isointense to the muscle on T1-weighted MR images, hyperintense to the muscle on T2-weighted MR images, and showed homogeneous, strong enhancement on contrast-enhanced T1-weighted MR images. The linear hypointense signal in an arborizing pattern was observed within the mass on all pulse sequences.

Castleman’s disease is a rare lymphoproliferative disorder of uncertain cause characterized by a distinctive pattern of hypervascular lymphoid hyperplasia (1). Although it is usually reported as a solitary mediastinal mass, involvement of other anatomic sites has been reported, with the head and neck being the second most common area (2). We describe a case of hyaline-vascular-type Castleman’s disease located in the retropharyngeal space.

A 34-year-old woman initially presented with a 5-year history of painless swelling on the right side of her oropharynx and a 2-year history of a slightly enlarging mass on the right side of her neck. Her medical history was unremarkable.

Unenhanced CT scans showed a large, well-circumscribed, solid mass in the right retropharyngeal space, which was isodense to the muscle. The mass showed homogeneous, strong enhancement on the contrast-enhanced CT scans

One month later, MR imaging was performed. On the MR images, the mass was located within the right retropharyngeal space, displacing the parapharyngeal fat anteriorly, the pharyngeal mucosal space medially, the styloid process anterolaterally, and the carotid space laterally. It was isointense to the muscle on the T1-weighted images (Fig 1B). There was a nonenhancing linear hypointense signal in an arborizing pattern within the mass on T1- and T2-weighted images (Fig 1C and D). The mass occupied the right retropharyngeal and parapharyngeal space from below the skull base to the hyoid bone level on the contrast-enhanced T1-weighted coronal image (Fig 1E). There was a small lymph node with a 1-cm diameter in the right internal jugular chain just below the main mass.

Excision of the neck mass was performed via a transcervical approach. A 5 x 8-cm, well-encapsulated, ovoid mass was removed without much difficulty. Histopathologic evaluation revealed Castleman’s disease (giant lymph node hyperplasia) of the hyaline-vascular type (Fig 1F). The mass was thought to arise from the lateral retropharyngeal lymph node. The small lymph node just below the main mass was proved reactive hyperplasia without tumor cells.

In 1956, Castleman et al (3) described a group of patients with large thymoma-like masses in the anterior mediastinum, which they called mediastinal lymph node hyperplasia. The cause of Castleman’s disease is uncertain; it is thought to be inflammatory or hamartomatous in nature (4, 5). Two distinct histologic variants are recognized (4). The most common is the hyaline-vascular type (more than 90% of the cases), which consists of small lymphoreticular follicles distributed within a hypervascular hyalinized stroma. The plasma cell type is less common (fewer than 10% of the cases) and consists of larger lymphoreticular nodules that are separated by sheets of plasma cells and a somewhat less vascular stroma. Patients with the hyaline-vascular-type disease are usually asymptomatic, but they may complain of symptoms caused by the compression of adjacent structures or may present with a palpable mass. Systemic manifestations are commonly seen in the plasma cell type and include fever, anemia, and hyperglobulinemia.

Castleman’s disease is usually limited to one site, although an aggressive multicentric form has been described. The most common site is the mediastinum (approximately 70%). Additional sites of occurrence include the axilla, retroperitoneum, mesentery, vulva, pancreas, pelvis, and neck (1, 4). Fewer than 10% of cases arise in the head and neck (6-11). In our case, the tumor was located within the right retropharyngeal space. It was thought to arise from a retropharyngeal node, probably the lateral group, which is located at the anterolateral aspect of the prevertebral muscle, although a carotid space origin could not be completely excluded. Several cases of Castleman’s disease involving the retropharyngeal or parapharyngeal space, medial to the carotid sheath, as in our case, have been reported (7-9).

The typical CT findings of Castleman’s disease are a well-marginated, homogeneous, and densely enhancing mass (6, 7), although ring enhancement can also be seen (1, 10). The hyaline-vascular variant tends to show more prominent enhancement on CT scans, most likely because of its greater vascularity (1, 10).

Typically, Castleman’s disease appears on MR images as low-to-intermediate signals compared with muscle on T1-weighted images and high signals on T2-weighted images (7, 9). In a few previous reports (12, 13), linear, arborizing, hypointense signals within the mass have been attributed to calcification, fibrous septations, vessels, or sinus histiocytosis. The linear hypointense signals seen on MR images in our case were proved perivascular lamellar fibrosis on pathologic correlation (Fig 1G). These linear hypointense signals could be an important clue to the diagnosis of Castleman’s disease, although they occur infrequently.

The MR imaging differential diagnoses for Castleman’s disease include paraganglioma and schwannoma. Paragangliomas in this area usually displace the internal carotid artery anteriorly because the tumor arises around the vagus nerve. Furthermore, paragangliomas have multiple focal and serpentine areas of low signal intensity, representing vascular flow voids within the mass, especially in large lesions. Schwannomas that arise from the vagus nerve and the sympathetic chain usually displace the internal carotid artery anteriorly because these nerves are posterior to this vessel. Frequently, schwannomas have inhomogeneous signal intensity due to cystic change. These features could be the clue to the differential diagnosis, with Castleman’s disease in the retropharyngeal or parapharyngeal space.

Complete surgical excision is the treatment of choice for Castleman’s disease in the head and neck, with a 100% control rate for the hyaline-vascular type. The plasma cell type, however, requires excision with close follow-up and possible systemic chemotherapy (14). Malignant transformation or association with other malignancies is rare and includes plasmacytoma, malignant lymphoma, and Kaposi’s sarcoma (15). Its malignant potential, although rare, raises suggestions of a relationship with an immune dysfunction or even primary lymphoproliferative disorder (16).

Castleman’s disease is a rare mass, which may involve the retropharyngeal space. On CT scans, it appears as a well-marginated, homogeneously enhancing mass. It has an isointense signal compared with muscle on T1-weighted MR images and a hyperintense signal compared with muscle on T2-weighted MR images, with homogeneous, strong enhancement. Linear hypointense signals in an arborizing pattern may be present within the mass. Castleman’s disease should be considered in the differential diagnosis of masses involving the retropharyngeal space.

1.                    Chaloupka JC, Castillo M, Hudgins P. Castleman disease in the neck: atypical appearance on CT. AJR Am J Radiol 1990;154:1051-1052[Free Full Text]

2.                    Frizzera G. Castleman’s disease: more questions than answers. Hum Pathol 1985;16:202-205[Medline]

3.                    Castleman B, Iverson L, Menendez VP. Localized mediasinal lymph node hyperplasia resembling thymoma. Cancer 1956;9:822-830[Medline]

4.                    Keller AR, Hochholzer L, Castleman B. Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer 1972;29:670-683[Medline]

5.                    Johnson JT, Oral A, Nalesnik M, Roscoe GJ, Whiteside TL. Giant lymph node hyperplasia: clinical and immunohistologic correlation of an intermediate variant. Ear Nose Throat J 1985;64:249-254[Medline]

6.                    Koslin DB, Berland LL, Sekar BC. Cervical Castleman disease: CT study with angiographic correlation. Radiology 1986;160:213-214[Abstract]

7.                    Freeman SJ, Irvine GH, Glew D. Case report: cervical Castleman’s disease shown by CT and MRI. Clin Radiol 1994;49:721-723[Medline]

8.                    Lanier BJ, Cummings CW. Giant lymphoid hyperplasia presenting as a highly vascularized parapharyngeal mass. Otolaryngol Head Neck Surg 1982;90:426-430[Medline]

9.                    Tuerlinckx D, Bodart E, Delos M, Remacle M, Ninane J. Unifocal cervical Castleman disease in two children. Eur J Pediatr 1997;156:701-703[Medline]

10.                 Nunna SV, Sharma R, Goyal M, Berry M, Gupta SD, Deshpande V. Unusual computed tomography appearance of Castleman disease. Australas Radiol 1997;41:193-195[Medline]

11.                 Gleeson MJ, Cassidy M, McMullin JP. Castleman’s disease: an unusual neck mass. J Laryngol Otol 1988;102:661-662[Medline]

12.                 Glazer M, Rao VM, Reiter D, McCue P. Isolated Castleman disease of the neck: MR findings. AJNR Am J Neuroradiol 1995;16:669-671[Abstract]

13.                 Luburich P, Nicolau C, Ayuso MC, Torra R, Clavero JA. Pelvic Castleman disease: CT and MR appearance. J Comput Assist Tomogr 1992;16:657-659[Medline]

14.                 Sanz C, Sierra J, Cobarro J, Avellaneda R, Montserrat E, Rozman C. An unusual case of Castleman’s disease restricted to the neck. ORL J Otorhinolaryngol Relat Spec 1992;54:331-333[Medline]

15.                 Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises (Case 32–1984). N Engl J Med 1984;311:388-398[Medline]

16.                 Williams JL, Kaude JV. Sonographic findings in a case of Castleman disease of the neck. J Ultrasound Med 1986;5:593-594[Medline]

Received November 8, 1999; accepted after revision January 18, 2000.

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Joseph T. Beck, Su-Ming Hsu, John Wijdenes, Regis Bataille, Bernard Klein, David Vesole, Katherine Hayden, Sundar Jagannath, and Bart Barlogie

Castleman’s disease (angiofollicular lymphoid hyperplasia) is a heterogeneous group of lymphoproliferative disorders of uncertain cause¹. Two pathologic types, hyaline vascular and plasma-cell disease, have been recognized. The plasma-cell variant of Castleman’s disease may be localized or multicentric. Multicentric disease is a systemic lymphoproliferative disorder characterized by lymphadenopathy, hepatosplenomegaly, and constitutional symptoms. Anemia, hypoalbuminemia, and hypergammaglobulinemia are also common. Interleukin-6, a cytokine with pleiotropic effects on the immune system, hematopoiesis, and acute-phase reactions, is a putative growth factor in multiple myeloma and may also be central to the pathophysiology of Castleman’s disease^2,3,4,5,6,7. Administration of a murine anti-interleukin-6 monoclonal antibody (BE-8) was reported to have a transient beneficial effect in one patient with plasma-cell leukemia⁸.

We treated a man who had Castleman’s disease and an elevated serum interleukin-6 concentration with a prolonged course of BE-8 monoclonal antibody. The symptoms and signs of disease resolved, and most of the abnormal laboratory values improved dramatically within a few days, but the abnormalities returned on cessation of therapy. Because of a persistent mesenteric mass, the patient was treated with high-dose dexamethasone. Ultimately, the mass was resected, resulting in a sustained remission of all clinical and biochemical manifestations of the disease.

Methods

BE-8 monoclonal antibody⁹ was administered in a dose of 40 mg given intravenously during a one-hour period daily for 2 days, followed by daily doses of 10 mg given intravenously for 82 days. Serum interleukin-6 concentrations were determined with an enzyme-immunoassay kit (Amgen, Thousand Oaks, Calif.). Tissue sections from the patient were used to study cytokine expression in situ. The sections were fixed with B5 (a mercury-based fixative) and embedded in paraffin. To determine the distribution of cells in the tissue sections, staining was performed with monoclonal antibodies that are reactive with B cells (L26, CD20), T cells (Leu-22, CD43), histiocytes (Ki-M1P), plasma cells (cytoplasmic immunoglobulin), or follicular dendritic cells (S-100). The expression of interleukin-6 by lymphoid cells or histiocytes was determined by immunostaining with rabbit antihuman interleukin-6 antibody (Genzyme, Boston), by means of the avidin-biotin-peroxidase method¹⁰. The anti-interleukin-6 antibody was added at a dilution of 1:100, followed by the addition of biotin-labeled goat antirabbit immunoglobulin (dilution, 1:400). After the tissue sections had been washed, they were incubated with avidin-biotin-peroxidase, and the reaction was developed with diaminobenzidine. The sections were then counterstained with hematoxylin, dehydrated, and cleared as in routine processing. In addition, paraffin sections were immunostained for interleukin-1, -4, -7, -8, and -9; granulocyte colony-stimulating factor; and granulocyte-macrophage colony-stimulating factor, as previously described¹¹.

Case Report

A 27-year-old man saw his physician in March 1987 because of a persistent cough, fatigue, and anemia. He had no history of syphilis or autoimmune diseases, such as rheumatoid arthritis or systemic lupus erythematosus. The physical examination was normal. The patient’s hemoglobin concentration was 7.6 g per deciliter (4.7 mmol per liter), the mean corpuscular volume was 57 microm³, the platelet count was 733,000 per cubic millimeter, the serum iron concentration was 25 µg per deciliter (4.5 µmol per liter), the total iron-binding capacity was 330 µg per deciliter (59 µmol per liter), and the ferritin concentration was 283 ng per milliliter. The bone marrow examination was normal. No specific diagnosis was made, and the patient was followed.

In November 1987, a computed tomographic (CT) scan of the abdomen showed a mesenteric mass measuring 10 by 14 by 4 cm. The patient underwent an exploratory laparotomy in December 1987 with a biopsy of the mesenteric mass and liver and a splenectomy. A histologic examination of the biopsy specimens revealed the plasma-cell variant of Castleman’s disease in the mass and liver; the spleen was normal. The patient was followed with CT scanning but received no systemic therapy. The remaining mesenteric mass and the hemoglobin concentration were stable until July 1990, when the patient was referred to the University of Arkansas Cancer Research Center.

At that time, the patient reported fatigue and had a low-grade fever (temperature, 37.8 °C). The physical examination was normal. A chest roentgenogram revealed no abnormalities, and repeated blood cultures were negative. Abnormal laboratory values included a hemoglobin concentration of 9 g per deciliter (5.6 mmol per liter), a white-cell count of 14,600 per cubic millimeter, a platelet count of 1,360,000 per cubic millimeter, a total serum protein concentration of 8.6 g per deciliter, an albumin concentration of 2.1 g per deciliter with polyclonal hypergammaglobulinemia (3.5 g per deciliter) on serum protein electrophoresis, an alkaline phosphatase concentration of 440 U per liter (7.3 microkat per liter), an interleukin-6 concentration of 45 pg per milliliter, and a C-reactive protein concentration of 16.7 mg per deciliter. Monoclonal plasma cells were not detected by flow-cytometric studies of bone marrow specimens; immunoelectrophoresis of serum and urine samples did not disclose monoclonal gammopathy. On review, the biopsy specimens of the mesenteric mass from December 1987 were interpreted as showing mixed plasma-cell and hyaline vascular variants of Castleman’s disease, and the liver-biopsy specimens were interpreted as normal.

With the approval of the institutional review board and the consent of the patient, he was treated with BE-8 monoclonal antibody for 84 days. His fever and constitutional symptoms improved within 24 hours; however, one to two weeks were required for the hemoglobin concentration to increase and for the platelet count to decrease (Figure 1). The serum interleukin-6 concentration increased markedly during therapy and returned to the base-line value after the treatment had been discontinued; the mesenteric mass did not change. Fever, constitutional symptoms, anemia, thrombocytosis, and other biochemical abnormalities recurred within a few days after the therapy had been discontinued. The patient was then treated with three cycles of dexamethasone at 35-day intervals. During each cycle, an oral dose of 40 mg of dexamethasone was given daily for four days on three occasions, each separated by four days. This treatment had little effect on symptoms, laboratory values, or the mesenteric mass. Approximately two and a half months later, the mass was resected. No clinical or biochemical signs of disease remained after the operation (Figure 1). The mesenteric mass proved to be a mass of lymph nodes and showed mixed hyaline vascular and plasma-cell Castleman’s disease on histologic examination

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Of Love, we begin our 67^th year of publication. We are informed the publication is one of the oldest continuing religious publications registered by the post office.

The Banner of Love has its roots in a publication called “The Glad Tidings”. It was started early in the century by Elder Wade Hampton Richards, my great-grandfather, assisted by his sons. It published for a number of years, but was a victim of the great Depression.

In about 1933, one of the sons, Elder Hardon G. (”Hard”) Richards, received the opportunity to get out of farming and back into the printing business. He and his family took over a small weekly newspaper which had suffered foreclosure. With a pocketful of one-letter-at-a-time handset type, the family learned the weekly newspaper business, and started from scratch another church publication.

My grandfather, like his father, was not interested in publicizing the religious disagreements of the time. He wanted to publish the good news of the church, and to discuss the great joys of the gospel, as his father had done with “The Glad Tidings.”

My grandmother named the new publication “The Banner of Love” after passages from Songs of Solomon 2:4 and Psalms 60:4.

With this issue, we again dedicate ourselves to the original purposes of this newspaper: to bring the good news to the readers, and avoid the issues that divide and disturb. It is not always easy.

Our worldly training and education is in journalism and law. In those professions, we find ourselves regularly engaged in the issues of the day. In such roles we are trained not to shy away from issues which may be controversial or present a “bad” picture on news. However, our philosophy with the Banner of Love is not of conventional journalism.

With the Banner of Love, we regularly receive articles submitted which may address some ongoing controversies of various churches or groups or assemblies. The publication of such matters was not the originating philosophy of this paper; and we hope to maintain the original goals. We are regularly challenged on this very matter.

We are required to make certain editorial decisions that try our conscious. Our goal is to give our readers good news and not have to worry or have any concern that when they open The Banner of Love, they can enjoy the fruits of the kingdom without being engaged over disputes that detract from that goal.

We make mistakes. When we do, we hope it is because we err on the side of caution. In pursuit of our goal, from time to time we feel compelled to refuse to publish certain articles submitted to us. We know we are privately criticized from time to time because of our conservative, tight philosophy in this regard.

Our philosophy can be explained very simply: the Banner of Love is not a battleground. It is a parade ground for articles of inspiration and explanation of the fruits of the spirit.

With this first issue of the new year, we renew our pledge to three basic philosophies, two civic and one religious:

1. First Amendment. First, we strongly support the civic privileges guaranteed in the First Amendment to the Constitution of the United States. We thus enjoy civil rights that were not guaranteed in the days of Christ: freedom of religion, freedom of speech and press, and the right of assembly. We thus are “guaranteed” the right to enjoy our own religion — even in a time when we witness literally thousands of versions of religious philosophies. With this guaranteed personal civic right comes the corresponding civic duty to respect the rights of other Americans to enjoy the choice of their religious philosophies, or not have a religion at all.

Our rights of free speech protects our many wonderful writers who submit articles for publication to express their personal faith and philosophies. The right of assembly give us a guarantee that we can meet together in groups or in organized churches and worship without government prosecution. Our right of free press gives us the opportunity to present to our readers the Banner of Love without controls or censorship from government. This philosophy allows us to establish our policy of “good news” for our readers.

2. Church and State. To insure these rights are protected and prolonged, we also believe in the philosophy of separation of church and state. We are not all too disturbed by judicial rulings which enforce this concept.

While it may, on the surface, appear as an attack on religion, it is actually a guarantee of religious freedom to insure some unwanted religious philosophy is not forced upon me or my family. In this regard, there is nothing in any judicial ruling which prohibits or unduly limits my personal right to worship or believe as I choose. The only basic restriction is that teachers, or other government-employed individuals cannot require we participate in, or be subjected to, a specific religious event or activity.

No one in our government, has ever stopped any of us from praying to our God whenever and where ever we choose. We should teach this to our children. Each of us has prayed in some unusual places, at unusual times. I have prayed in classrooms, and I have prayed in courtrooms. Nothing stops us from teaching and giving examples of this to our children or to others.

3. Religious Philosophy. Exercising our religious freedom, we believe in the religious doctrine generally outlined in the “Articles of Faith” of the Primitive Baptist Church. We will not restate them today in this column, but are guided by these basic religious concepts in our attempts to write and edit The Banner of Love in accordance with our basic rights of free speech and press.

The most fundamental aspect of this religious philosophy is the doctrine of “sovereign grace” — that being that our Lord is the controller of our eternal fate according to His purpose. (Rom. 8:28). Our eternal destiny is subject to His unconditional love and grace, which was established before each of us was born, or the world formed. (Rom. 9:11; Eph 1:4, 2:8-10; II Tim. 1:7-10; Titus 3:3-8) No man, even ourselves, rises to a level in God’s eyes to be able to earn or justify our own eternal salvation.

Readers of The Banner of Love should expect to see these basic concepts followed in our editorial philosophies.

Finally, we are indebted to our generous writers. We would not have a newspaper without them. The inspiration in our writers is evident and we encourage and pray for their continued support.

We request your prayers that the will of the Lord will be displayed in all our efforts. It is all in His name; all glory to Him.

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Above Ourselves

February 2000