Castleman disease

Anatomy and physiology of lymph nodes

Lymph nodes are essential peripheral lymphoid organs. Structurally, they consist of various cell types, predominantly of the immune system, which provide a barrier function. The angioarchitecture of a lymph node is closely linked to the circulatory system. In addition, the nodes are connected into a single network via afferent and efferent lymphatic vessels. This complex communication system allows them to effectively filter lymph and rapidly respond to any foreign antigens.

Main mechanisms of lymphadenopathy development

Enlargement of lymph nodes (lymphadenopathy) can develop through several fundamentally different pathogenetic scenarios. Understanding these mechanisms is critically important for differential diagnosis:

1. Reactive states. Occur as an adequate immune response to antigen invasion. Manifested by an increase in the pool of benign cells. This can be an increase in the number of lymphocytes (morphologically described as follicular hyperplasia or paracortical hyperplasia) or an increase in the number of macrophages (sinus histiocytosis).
2. Lymphadenitis. Represents classic inflammation. In infectious processes, the lymph node tissue is heavily infiltrated by inflammatory cells.
3. Storage diseases. In this case, lymph nodes enlarge due to massive macrophage infiltration. These cells become overloaded with specific metabolic products (a similar picture may also be observed in certain tumors).
4. Malignant proliferation in situ. Primary neoplastic transformation of the lymph node's own cells. Characteristic of leukemias, Hodgkin disease, and various types of non-Hodgkin lymphomas.
5. Metastasis. Secondary involvement where malignant tumor cells of various histogenesis from other organs are seeded into the lymph node.

Castleman disease: general characteristics and synonyms

Against the background of the mechanisms described above, Castleman disease (or angiofollicular lymph node hyperplasia) stands out as a distinct nosological entity. This is a fairly rare lymphoproliferative disorder of a strictly non-malignant nature. Clinically and morphologically, it manifests as a very significant, yet extremely uneven, enlargement of lymph nodes.

In medical practice, a number of synonyms are used to refer to this pathology: giant lymph node hyperplasia, Castleman pseudotumor, and lymphoamartoma. Despite the alarming size of the nodes, cytogenetic abnormalities that are markers of true malignant growth are extremely rarely detected in this disease.

Etiology and molecular pathogenesis

Although the exact causes of the disease continue to be studied, current data indicate a leading role for viral agents and cytokine regulation disorders.

• Process inducers: Human herpesvirus type 8 (HHV-8, or HHV-8) is considered the primary suspected culprit. This pathogen is capable of causing so-called slow infections. In addition to the herpesvirus, retroviral infections or other potent antigenic stimuli may act as inducers.
• Pathogenesis: In response to viral invasion or antigenic stimulation, a pathological cascade is triggered, the central link of which is the overproduction of interleukin-6 (IL-6). It is this cytokine that acts as the main driver of massive lymphoproliferation, leading to the formation of giant lymph nodes.
• Prognosis: The disease follows a benign course. Transformation of hyperplastic tissue into overtly malignant forms (lymphoma or plasmacytoma) occurs very rarely.

Localization of lesions and clinical types

The pathological process in Castleman disease may affect lymph nodes in various parts of the body, yet a certain pattern exists:

• Common localization: intrathoracic lymph nodes (within the lungs), neck region, supraclavicular spaces, and the mesentery of the small intestine.
• Rare localization: axillary vaults, pelvic lymph nodes, and the pancreas zone.
• Extremely rare localization: generalized (total) enlargement of lymph nodes in all parts of the body simultaneously.

Depending on the histological structure and clinical features, three main types of the disease are distinguished:

1. Hyaline-vascular type.
2. Plasma cell type.
3. Multicentric type.

Class and exam questions

What else to study on this topic

• Morphological differences between hyaline-vascular and plasma cell types.
• The role of HHV-8 in the pathogenesis of slow infections.
• Differential diagnosis with Hodgkin lymphoma and non-Hodgkin lymphomas.
• Mechanisms of reactive follicular hyperplasia and the paracortical zone.
• Sinus histiocytosis: causes and morphology.

Other topics in Hematopoietic System Diseases

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.