d cell lymphoma | Hodgkin lymphoma (Hodgkin's disease)

Hodgkin lymphoma
(Hodgkin's disease)




by Carol S. Portlock, MD, professor of clinical medicine, Weill Cornell University Medical College; Treating physician, lymphoma service, Memorial Sloan-Kettering Cancer Center


Hodgkin's lymphoma is a malignant, localized or disseminated proliferation of lymphoreticular system cells, mainly affecting the lymph nodes, spleen, liver, and bone marrow. Symptomatology includes the presence of a painless lymphadenopathy, sometimes associated with fever, night sweats, unintentional weight loss, pruritus, splenomegaly and hepatomegaly. The diagnosis is based on ganglionic biopsy. Treatment, curative in nearly 75% of cases consists of chemotherapy with or without radiation therapy.

In the United States, about 9000 new cases of Hodgkin's lymphoma are diagnosed annually. The male: female ratio is 1.4:1. Hodgkin's lymphoma, rare before 10 years, is most common between 15 and 40 years; With a 2nd pic > 50 to 60 years.

Pathophysiology
Hodgkin's lymphoma results from the clonal transformation of lymphoid cells belonging to the B line, giving rise to the binucleate cells of Reed-Sternberg, pathognomiques of the disease. The cause is unknown, but there is a genetic predisposition and environmental associations play a role (e.g., professional, such as woodworking; History of treatment with phénylhydantoïne, radiotherapy, Chemotherapy Epstein-Barr virus infection, by Mycobacterium tuberculosis, herpesvirus 6, HIV). The risk is slightly increased in people with certain acquired immune deficiency (e.g., transplanted patients receiving immunosuppressants); In people with congenital immune deficiency (e.g., ataxia-telangiectasia, Klinefelter syndrome, Chédiak-Higashi, Wiskott-Aldrich); And in people with certain autoimmune diseases (rheumatoid arthritis, celiac disease, syndrome, lupus erythematosus).

Most patients also develop a slowly progressive deficit of cellular immunity (T lymphocyte function), which contributes to the common germ bacterial infections and unusual fungal, viral or parasitic infections Observed in the advanced stages of the disease. Humoral Immunity (production of Ac) is also altered at these advanced stages. Death is often caused by a sepsis.

Symptomatology
Most patients show up with a painless cervical lymphadenopathy. Although the mechanism is not clear, pain can occur in the territory reached immediately after the absorption of alcoholic beverages, orienting the diagnosis early.

Other manifestations occur as the disease is disseminated in the Reticulo-endothelial system, usually by adjacency. Intense pruritus can occur early. General symptoms combine fever, night sweats and unintentional weight loss (> 10% of body weight in the last 6 months) and may reflect the presence of deep adenopathies (mediastinal or metastasis), Visceral (liver) or medullary impairment. A splenomegaly is common; A hepatomegaly can be present. A Pel-Ebstein fever (a few days of high fever regularly alternating with a few days to a few weeks of normal temperature or below normal) is sometimes observed. Wasting occurs frequently with the progression of the disease.

Bone impairment is often asymptomatic, but can result in ostéocondensantes vertebral lesions (ivory vertebrae) or, more rarely, painful osteolytic lesions with a settlement fracture. Intracranial, gastric or cutaneous lesions are rare and orient to Hodgkin's lymphoma associated with HIV infection.

Tumor masses can be compressive and thus cause symptoms such as

Jaundice secondary to an obstruction of the bile ducts intra-or hepatic

Lower limb edema secondary to pelvic or femoral lymphatic obstruction

Severe dyspnea with wheezing secondary to tracheobronchial compression

Excavated lesions or secondary pulmonary abscesses with parenchymatous infiltration, which can simulate lobar condensation or bronchopneumonia

Epidural invasion of the spinal cord can lead to paraplegia. A syndrome of Claude Bernard-Horner and laryngeal paralysis can result from the cervical compression of the sympathetic or recurrent nerve by tumor lymph nodes. The compression of the nerve roots causes a very sensitive pain.

Diagnosis
Rx Thorax

CT of the thorax, and abdominal-pelvic

NFS, determination of alkaline phosphatases and LDH, hepatic balance, determination of albumin, Ca, urea, and serum creatinine

lymph node biopsy

PET for stage and MRI classification if neurological symptoms are present

Sometimes bone marrow biopsy

The diagnosis of Hodgkin's lymphoma is usually evoked in case of painless peripheral lymphadenopathy or lymphadenopathy mediastinal discovered on the occasion of a routine rx thorax. Such lymphadenopathy may be due to infectious mononucleosis, toxoplasmosis, cytomegalovirus infection, non-Hodgkin's lymphoma or leukemia. An aspect similar to the RX thorax may be due to lung cancer, sarcoidosis or tuberculosis (for the balance of a mediastinal mass, mediastinal Masses: Diagnosis).

Hodgkin lymphoma (lymphadenopathy mediastinal) Hodgkin's lymphoma (Lymphadenopathy mediastinal) Hodgkin's lymphoma (Lymphadenopathy mediastinal)

DR. P. Marazzi/SCIENCE PHOTO LIBRARY

If it has not already been performed, an RX thorax is performed. The RX is usually followed by a ganglionic biopsy if the results are confirmed by CT or the thorax's PET. If only the mediastinal ganglia are increased by volume, a mediastinoscopy or a Chamberlain intervention (anterior left needle thoracostomy Limited, allowing the biopsy of mediastinal ganglia inaccessible by cervical mediastinoscopy) are indicated. A CT-guided biopsy may also be considered, but the results of fine-needle cytoponctions are often inconclusive, and a ganglionic biopsy at the trocar is therefore necessary. An NFS, a dosage of alkaline phosphatases, a renal and hepatic balance are generally practiced. Additional examinations are carried out on the basis of signs (e.g., MRI in case of symptoms of medullary compression).

The biopsy shows cells of Reed-Sternberg (large binucleate cells) in a characteristic heterogeneous cell infiltration composed of histiocytes, lymphocytes, monocytes, plasma and eosinophils. Classical Hodgkin's lymphoma comprises 4 histopathological subtypes (see Histopathological types of Hodgkin's lymphomas (who classification)); There is also a predominantly lymphocytic nodular type. Some Ag present on Reed-Sternberg cells are used to differentiate between NHL Hodgkin lymphomas and classical Hodgkin lymphoma of the predominantly lymphocytic nodular type.

Under Histopathological types of Hodgkin's lymphomas (who classification)

Histological Type

Morphological Aspect

Immunophénotype of tumor cells

Impact

Classic

Nodular sclerosis

Dense fibrous tissue * cutting the ganglionic parenchyma into Hodgkin's tissue nodules

CD15 +, CD30 +, CD20 –

67%

Mixed cellularity

Within a polymorphic cell population, presence of a moderate number of Reed-Sternberg cells

CD15 +, CD30 +, CD20 –

25

Rich in lymphocytes

Few Reed-Sternberg cells

Many B lymphocytes

Fine Sclerosis

CD15 +, CD30 +, CD20 –

3

Lymphocyte depletion

Reed-Sternberg's many cells

Extensive fibrosis

CD15 +, CD30 +, CD20 –

Rare

Predominantly lymphocytic nodular

Few neoplastic cells (lymphocyte cells and/or histiocytic)

Many small B lymphocytes

Nodular appearance

CD15 –, CD30 –, CD20 +, EMA +

3

* shows a characteristic birefringence to polarized light.

EMA = Ag epithelial membrane (epithelial membrane antigen).

Reed-Sternberg cells Reed cells-Sternberg reed cells-Sternberg

Courtesy of the FDA.

Other tests may be abnormal but are not diagnostic. The NFS can reveal a slight leukocytosis to polynuclear neutrophils. A lymphopenia can appear early and worsen with the evolution of the disease. A eosinophilia is found in nearly 20% of patients, a thrombocytosis can also be present. Anemia, often microcytic, usually develops at the advanced stages of the disease. It then results from a defect in iron reuse, characterized by a decrease in serum iron and iron fixation capacity, while the medullary iron is increased. Medullary flooding, most often occurring in lymphocyte-depleted forms, can sometimes cause pancytopenia. A hypersplenism (hypersplenism) can be observed in case of significant splenomegaly. An increase in serum alkaline phosphatases may be observed, but does not necessarily indicate a medullary and/or hepatic impairment. The elevation of leucocyte alkaline phosphatases, serum haptoglobin, and other acute inflammatory markers are usually indicative of an active disease.

Stadium Classification

Once the diagnosis is established, the stage is determined to guide the treatment. The commonly used system is the not Ann Arbor stage classification (see Cotswold Modification of the Ann Arbor classification of Hodgkin and non-Hodgkin lymphomas) that incorporates symptoms; Signs of clinical examination Imaging, including RX thorax, thoracic ct, and abdominal and pelvic and PET; And more rarely the unilateral bone marrow biopsy. Laparotomy is not required for stage classification. Other elements of the stage evaluation are the cardiac and respiratory functional tests carried out with pre-therapeutic aim. The Cotswold changes in the ANN Arbor classification additionally incorporate the prognostic value of the tumour mass of the tumor and the sites of the disease.

Modification of Cotswold of the Ann Arbor stage classification of Hodgkin and non-Hodgkin lymphomas

Stage

Criteria

I

In one node area

Ii

In ≥ 2 ganglion areas on the same side of the diaphragm

Iii

In the lymph nodes and/or spleen, and on both sides of the diaphragm

Iv

Extraganglionnaire impairment (e.g., bone marrow, lungs, liver)

* Sub-classification E means a extraganglionnaire impairment in the continuity of an invaded ganglion (e.g., a disease associating adenopathies mediastinal and hilaires an adjacent pulmonary infiltration will be classified as IIE). The stages can be classified A if there are no general signs or B if there are general signs (weight loss, fever or night sweats). General signs are usually found in stages III and IV (20 – 30% of patients). The suffix X is used to refer to a large mass (bulky), that is to say, a maximum dimension of 10 cm or that comprises more than 1/3 of the thoracic diameter (at the RX thorax).

The denomination by the letter A means, whatever the stage, that there is no general sign. The denomination by the letter B means that at least one general sign is present. The evolution of the general signs is correlated with the response to the treatment.

Prognosis

In Hodgkin's lymphoma, disease-free survival 5 years after treatment is considered a cure. Relapse are very rare after five years. Chemotherapy with or without radiation therapy provides a cure for 70 to 80% of patients. A high risk of relapse depends on many factors, including male, an age of 45 years, a extraganglionnaires of several sites and the presence of general signs at the time of diagnosis. Failure to obtain a full remission or relapse within 12 months is a bad prognosis.

Clinical calculator: International prognostic Score in Hodgkin's lymphoma

Treatment

Chemotherapy

Radiotherapy

Surgery

Sometimes, hematopoietic stem cell transplantation

The choice of therapeutic modalities is complex and depends on the precise stage of the disease. Before treatment, men should be offered a cryopreservation of sperm, and women should discuss fertility options with their oncologist.

Stages IA, IIA, IB or IIB of the disease are generally treated with a limited number of polychemotherapy cycle including doxorubicin (Adriamycin), bleomycin, Vinblastine and Dacarbazine (ABVD) followed by radiotherapy. This treatment allows healing in about 80% of cases. In the case of large mediastinal mass, chemotherapy may be prolonged or of a different nature and radiotherapy is typically used.

Stages IIIA and IIIB are usually treated with ABVD association chemotherapy alone. Recovery rates of 75 to 80% were achieved in the patient at stage IIIA of the disease, and rates from 70 to 80% in the patient at stage IIIB.

For the IVA and IVB stages, a ABVD-type polychemotherapy has become the reference treatment, allowing a complete remission in 70 to 80% of patients; > 50% are in remission at 5 years. Other effective medications include nitroso-ureas, Ifosfamide, Procarbazine, cisplatin or carboplatin and etoposide. Other drug combinations are bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), Procarbazine and Prednisone (association known as BEACOPP), and Melchloréthamine, doxorubicin, Vinblastine, vincristine, etoposide, bleomycin and prednisone (association known as Stanford V). The Stanford V incorporates irradiation of areas initially invaded in consolidation.

Post-therapeutic Surveillance of Hodgkin lymphomas

Balance sheet

Table

Background and clinical examination, NFS, platelets, ionogram, urea, serum creatinine, hepatic balance

First 2 years, Q 3  u20124 months

Year 3 to 5, q 6 months

> 5 years, q 12 months

Rx thorax at each consultation when the CT of the thorax is not carried out

First 2 years, Q 3 months

Year 3 to 5, q 6 months

CT of the thorax

First 2 years, Q 6 to 8 months

Years 3 to 5 years, annually

Abdominal-Pelvic CT

Stages I and II: First 5 years, annually

At other stages: first 2 years, Q 6 months

Years 3 to 5, annually

TSH levels

Every 6 months after irradiation of the neck

Mammography

Annually starting at 7 years in the event of Diaphragmatic irradiation having started < 30 years

Each year from the age of 37 years in the case of diaphragmatic irradiation having started ≥ 30 years

Breast MRI

In high-risk patients (those with diaphragmatic irradiation before the age of 30) alternating Q 6 months with mammography (a 6-month Q test)

An autografting of peripheral cells should be considered in all eligible patients with relapsed or refractory Hodgkin's lymphoma, which respond to remedial chemotherapy.

Complications of treatment

Chemotherapy, especially by medications such as Mechlorethamine, vincristine, procarbazine and prednisone, increases the risk of leukemia, which typically develops after 3 years. Both chemotherapy and radiation both increase the risk of malignant solid tumours (e.g., breast, gastrointestinal tract, lung, soft tissue). Mediastinal irradiation increases the risk of coronary artery atherosclerosis. The risk of breast cancer is increased in women within a period of approximately 7 years after radiotherapy of adjacent ganglion areas.

Monitoring after treatment

Surveillance is intended to detect a relapse. For a planning of post-therapeutic surveillance, see post-therapeutic surveillance of Hodgkin lymphomas.

Key Points

Hodgkin's lymphoma is of cell Origin B.

It is often discovered a painless lymphadenopathy or a mediastinal lymphadenopathy on an rx thorax.

The biopsy shows pathognomonic cells, binucleate from Reed-Sternberg.

The cure rate is overall from 70 to 80% using a chemotherapy association and sometimes radiation therapy.