• Information
  1. Introduction
  2. Hyaline-Vascular Type
  3. Plasma Cell Type
  4. Paraneoplastic Pemphigus

A. Introduction

1. Other Names
   1. Giant Lymph Node Hyperplasia
   2. Angiofollicular Lymphoid Hyperplasia
   3. Lymphoid Hamartoma
   4. Follicular Lymphoreticuloma
2. Lymphadenopathy present
3. Localized or Systemic
   1. Localized disease is curable with surgery
   2. Systemic disease responds better to multiagent chemotherapy than to single drugs
4. Histologic Subtypes
   1. Hyaline-Vascular Type (HV; 90% of cases)
   2. Plasma Cell Type
   3. Mixed Type - characteristics and treatment of combined HV and Plasma Cell types
   4. Mixed type strongly associated with human herpesvirus 8 (HHV-8) [2]
   5. Mixed type in HIV+ patients nearly always HHV-8+ and often with Kaposi's sarcoma [2]
5. Interleukin 6 (IL-6) overexpression in mice leads to disease similar to Castleman's [3]

B. Hyaline-Vascular Type

1. ~70% of patients present before age 30 years
2. Most are asymptomatic
3. Symptoms in minority of patients
   1. Usually due to compression of the tracheobronchial tree
   2. Cough, infection, shortness of breath
4. Diagnosis usually made accidently on chest radiograph (CXR) done for another reason
5. Differential of Thoracic Mass (on CXR)
   1. Lymphoma
   2. Sarcoidosis
   3. Thymoma
   4. Teratoma
   5. Thyroid Mass (Goiter, Neoplasm)
   6. Sarcoma
   7. Neurogenic Tumor
   8. Primary Lung Ca (unusual)
6. Pathology
   1. Highly vascular lesion
   2. 1.5-16cm mass, usually single LN
   3. Pathologic changes may be seen in adjacent LN
7. Diagnosis
   1. CT Scan - highly vascular lesion shows contrast enhancement
   2. Biopsy
8. Treatment
   1. Localized disease in all patients
   2. Surgical resection is curative
   3. Partial resection may be done with no risk of recurrence on followup

C. Plasma Cell Type

1. More common in elderly males
2. Localized, Systemic, or Mixed Types
   1. Most related to multiple myeloma
   2. Interleukin 6 overexpression is found in many cases of Castleman's Disease
3. Systemic Type usually has Symptoms and Signs:
   1. Fever, Sweats
   2. Fatigue
   3. Anemia - chronic disease type
   4. ~50% have elevated ESR and globulins, leukocytosis, thrombocytosis
4. Generally poorly vascular
   1. Localized form thought to represent inflammatory process with B cell hyperreactivity
   2. Systemic form thought of as lymphoproliferative disorder
   3. Poor contrast enhancement on CT
5. Treatment
   1. Surgical resection for localized disease (concern for progression)
   2. Ablative chemotherapy similar to lymphoma therapy
   3. CHOP or CVAD appears to be more effective than single agents for systemic disease [2]
   4. Survival for systemic Castelman Disease is 5-222 months (median 19 months)
   5. Murine anti-human IL-6 monoclonal antibody showed some benefit in two patients [4]

D. Paraneoplastic Pemphigus [5]

1. Autoimmune vesicular eruption usually associated with hematologic cancer
2. Autoantibodies specific for desmogleins 3 and 1, and bullous pemphigoid antigens 1 and 2
3. Additional autoantibodies to plakins and to 170K protein
4. Associated with some cases of Castleman's disease
5. Castleman's tumor cell antigens stimulate pathogenic IgG autoantibody formation
6. Oligoclonal activation of autoantibody producing B cells occurs
7. Painful mucous membrane ulcerations are often first manifestation
   1. Cutaneous lesions vary in shape and size, and may become confluent
   2. Erythematous maculopapular rash with bullous lesions developing
8. Tumor resection lead to clearing of cutaneous lesions in <11 weeks and mucosal lesions in <10 months

References

1. Herrada J, Cabanillas F, Rice L, et al. 1998. Ann Intern Med. 128(8):657
2. Scadden DT, Muse VV, Hasserjian RP. 2006. NEJM. 355(13):1358 (Case Record)
3. Brandt SJ, Bodine DM, Dunbar CE, Nienhuis AW. 1990. J Clin Invest. 86:592
4. Beck JT, Hsu SM, Wijdenes J, et al. 1994. NEJM. 330(9):602
5. Wang L, Bu D, Yang Y, et al. 2004. Lancet. 363(9408):525