Hodgkin's lymphoma overview

# Overview
Hodgkin's lymphoma was first described by Thomas Hodgkin, a British physician, in 1832. Since then, the tremendous efforts of many researchers have continued to provide more precise and comprehensive information regarding the pathology, staging, and treatment of Hodgkin's lymphoma. Hodgkin's lymphoma is a potentially curable tumor, in which malignancy originates from lymphocytes. According to the World Health Organization (WHO), Hodgkin's lymphoma (HL) can be classified into two major subgroups: nodular lymphocyte predominant and classic Hodgkin's lymphoma. Classic Hodgkin's lymphoma is further divided into four subtypes: nodular sclerosis classic HL (NSHL), mixed cellularity classic HL (MCHL), lymphocyte rich classic HL (LRHL), and lymphocyte depleted classic HL (LDHL). According to the Lugano classification and Cotswolds modifications of the original Ann Arbor staging system, there are 4 stages of Hodgkin's Lymphoma based on clinical features gathered from history and physical examination and findings on positron emission tomography/computed tomography (PET/CT) scan of the chest, abdomen, and pelvis. Each stage is assigned one letter and one number that designate the number of  lymph node regions involved and the presence/absence of systematic symptoms or of bulky or extended disease. On gross pathology, white-grey, uniform, and enlarged lymph nodes are characteristic findings of Hodgkin's lymphoma. On microscopic histopathological analysis, Reed-Sternberg cells, reactive cell infiltrate, and complete or partial effacement of the lymph node architecture are characteristic findings of Hodgkin's lymphoma. Hodgkin's lymphoma must be differentiated from sarcoidosis, lymphocytic lymphoma, miliary tuberculosis, infectious mononucleosis, thoracic aortic aneurysm, substernal goiter, thymoma, actinomycosis, chronic lymphocytic leukemia, superior vena cava syndrome, unicentric castleman disease, adult still disease, small cell lung carcinoma, and malignant histiocytosis. Hodgkin's lymphoma has a bi-modal age distribution that differs geographically and ethnically in industrialized countries with the first peak occurring in the middle-to-late 20's and the second peak occurring after age 50. In developing countries, the early peak instead occurs before adolescence. In 2015, the incidence of Hodgkin's lymphoma was estimated to be 3 cases per 100,000 individuals in the United States with a higher incidence among patients with HIV/AIDS. However, in contrast to many other lymphomas associated with HIV infection, Hodgkin's lymphoma occurs most commonly in patients who do not have severe immunosupression. The most common risk factors in the development of Hodgkin's lymphoma are the Epstein-Barr virus, family history, and HIV infection. Other possible risk factors include genetics, infectious mononucleosis, autoimmune diseases, immunodeficiency, tobacco usage, and socio-economic status. The 5-year survival rate of patients with Hodgkin's lymphoma varies with the stage of the disease, however the early stage is associated with the most favorable prognosis. The most common symptoms of classic Hodgkin's lymphoma include painless localized peripheral lymphadenopathy, B symptoms (fever, night sweats, and weight loss), and pruritus. Less common symptoms of Hodgkin's lymphoma include cough, chest pain, breathing problems, pain or feeling of fullness below the ribs, pain in lymph nodes after drinking alcohol, skin blushing or flushing, bone pain, and leg swelling. Common physical examination findings of Hodgkin's lymphoma include fever, lymphadenopathy, petechiae, jaundice, chest tenderness, wheezing, superior vena cava syndrome, abdominal tenderness, hepatomegaly, splenomegaly, fracture, peripheral lymphadenopathy, and central lymphadenopathy. The diagnostic study of choice for Hodgkin's lymphoma is lymph node biopsy. The presence of Reed-Sternberg cell is diagnostic for classic Hodgkin's lymphoma. In addition to light microscopy evaluation of the biopsy samples, the immunophenotypic analysis with immunohistochemistry helps to determine Hodgkin's lymphoma subtypes and distinguish Hodgkin's lymphoma from T cell rich large B cell lymphoma and anaplastic large cell lymphoma.  Laboratory tests for Hodgkin's lymphoma include complete blood count (CBC), blood chemistry studies, HIV blood test, immuno histochemistry, erythrocyte sedimentation rate, and immunophenotyping. On ultrasound, Hodgkin's lymphoma is characterized by hepatomegaly and splenomegaly. The optimal therapy for Hodgkin's lymphoma depends on the stage at diagnosis, age, type, and size of tumor but the predominant therapy for Hodgkin's lymphoma is chemotherapy. Adjunctive radiation therapy and stem cell transplant may also be required.

# Historical perspective
Hodgkin's lymphoma was first described by Thomas Hodgkin, a British physician, in 1832. Since then, tremendous efforts of many scientists have been continuing to provide more precise and comprehensive with pathology, staging, and treatment of Hodgkin's lymphoma. Since 1997 the World Health Organisation (WHO) has been involved in a project with committees of international hematopathologists and oncologists, who have developed lists and definitions of disease entities to ensure that the classification will be helpful to clinicians. They proposed their first approach in 2000 and after that, the relevant Clinical Advisory Committee (CAC) updates its latest revision every few years.

# Classification
According to World Health Organization (WHO) Hodgkin's lymphoma (HL) may be classified  classification into two major subgroups: nodular lymphocyte predominant and classic Hodgkin's lymphoma. Classic Hodgkin's lymphoma is further divided into four subtypes: nodular sclerosis classic HL (NSHL), mixed cellularity classic HL (MCHL), lymphocyte rich classic HL (LRHL), and lymphocyte depleted classic HL (LDHL).
According to the Ann Arbor Staging System with Cotswolds modifications, there are 4 stages of Hodgkin's Lymphoma based on clinical features gathered from history and physical examination, and findings on positron emission tomography/computed tomography (PET/CT) scan of the chest, abdomen, and pelvis. Each stage is assigned one letter and one number that designate the number of involved lymph node regions and the presence/absence of systematic symptoms or of bulky or extended disease.

# Pathophysiology
On gross pathology, white-grey, uniform, and enlarged lymph nodes are characteristic findings of Hodgkin's lymphoma. On microscopic histopathological analysis, Reed-Sternberg cells, reactive cell infiltrate, and complete or partial effacement of the lymph node architecture are characteristic findings of Hodgkin's lymphoma.

# Causes
There are no established causes for Hodgkin's lymphoma.

# Differential diagnosis
Hodgkin's lymphoma must be differentiated from sarcoidosis, lymphocytic lymphoma, miliary tuberculosis, infectious mononucleosis, thoracic aortic aneurysm, substernal goiter, thymoma, actinomycosis, chronic lymphocytic leukemia, superior vena cava syndrome, unicentric castleman disease, adult still disease, small cell lung carcinoma, and malignant histiocytosis.

# Epidemiology and Demographics
Hodgkin's lymphoma has a bimodal age distribution that differs geographically and ethnically in industrialized countries where the early peak occurs in the middle-to-late 20's and the second peak after the age of 50. In developing countries, the early peak occurs before adolescence. In 2015, the incidence of Hodgkin's lymphoma was estimated to be 3 cases per 100,000 individuals in the United States with the incidence of Hodgkin's lymphoma being higher among patients with HIV/AIDS. However, in contrast to many other lymphomas associated with HIV infection, Hodgkin's lymphoma occurs most commonly in patients who do not have severe immunosupression.

# Risk Factors
The common risk factors in the development of Hodgkin's lymphoma are the Epstein-Barr virus, family history, and HIV infection. Other possible risk factors include genetics, infectious mononucleosis, autoimmune diseases, immunodeficiency, tobacco, socio-economic status and family features.

# Screening
Screening for Hodgkin's lymphoma is not recommended.

# Prognosis
Hodgkin's lymphoma has a bimodal age distribution and both children and adult may be affected. The early peak occurs in the middle-to-late 20's and the second peak after the age of 50. Treatment outcomes of Hodgkins lymphoma are excellent and five-year survival rates are more than 80%. Due to modern therapies, the natural history of untreated Hodgkins lymphoma is actually difficult to determine. Survivors are at risk for relapse, second primary malignancies, cardiovascular complications and other treatment-related toxicities. Prognosis is based on the stage of the disease and other prognostic factors but the early stage of the Hodgkin's lymphoma is associated with the most favorable prognosis. The 5-year survival rate of patients with Hodgkin's lymphoma varies with the stage of the disease.

# Diagnosis

## Staging
According to the Lugano classification and Cotswold's modification of the original Ann arbor staging system, there are four stages of Hodgkin's lymphoma based on the number of nodes and extra nodal involvement.

## Symptoms
The most common symptoms of Hodgkin's lymphoma include fatigue, fever and chills, itching, loss of appetite, soaking night sweats, weight loss, and painless swelling of the lymph nodes in the neck, axilla, or groin (swollen glands). Less common symptoms of Hodgkin's lymphoma include cough, chest pain, or breathing problems, pain or feeling of fullness in abdomen, pain in lymph nodes after drinking alcohol, skin blushing or flushing, bone pain, and leg swelling.

## Physical Examination
Common physical examination findings of Hodgkin's lymphoma include fever, pruritus, petechiae, jaundice, chest tenderness, wheezing, superior vena cava syndrome, abdominal tenderness, hepatomegaly, splenomegaly, fracture, peripheral lymphadenopathy, and central lymphadenopathy.

## Laboratory Tests
Laboratory tests for Hodgkin's lymphoma include complete blood count (CBC), blood chemistry studies, HIV blood test, immunohistochemistry, erythrocyte sedimentation rate, and immunophenotyping.

## X Ray
Chest, spine, pelvic, and long bone x ray may be helpful in the diagnosis of Hodgkin's lymphoma.

## CT
Chest, abdomen, and pelvis CT scan may be helpful in the diagnosis of Hodgkin's lymphoma.

## MRI
Chest, abdomen, and pelvic MRI scan may be helpful in the diagnosis of Hodgkin's lymphoma.

## Ultrasound
On ultrasound, Hodgkin's lymphoma is characterized by hepatomegaly and splenomegaly.

## Biopsy
Lymph node or extra nodal tissue biopsy is diagnostic of Hodgkin's lymphoma.

## Other Imaging Tests
Chest, abdomen, and pelvis PET scan may be helpful in the diagnosis of Hodgkin's lymphoma. In some cases a Gallium Scan may be used instead of a PET scan.

## Other Diagnostic Studies
Other diagnostic studies for the diagnosis of Hodgkin's lymphoma include bone marrow biopsy, bone scan, lymphangiogram, or laparotomy.

# Treatment

## Medical Therapy
Hodgkin lymphoma is considered a curable cancer, however, treatment-related toxicities for this disease can be associated with significant long-term complications. Selection of treatment protocol for Hodgkin's lymphoma depends on the type, the stage at diagnosis, age, and size of the tumor. Combined modality therapy including use of chemotherapy and radiation therapy (RT) is the treatment of choice in patients with early-stage classic Hodgkin's Lymphoma.

## Surgery
Surgical intervention is not recommended for the management of Hodgkin's lymphoma.