Disease Site

Lymphomas are divided into two main groups: Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Anaplastic large cell lymphoma is classified under non-Hodgkin’s lymphoma. In anaplastic large cell lymphoma, the cancer cells are mainly of T cell and null cell types. Some HIV-related cases involve B cells.

Incidence

ALCL was only added as a separate entity to the revised Kiel classification in 1988. In 1994, it was included in the Revised European-American Lymphoma (REAL) classification.
ALCL accounts for about 2% of lymphomas, but represents 12% of childhood lymphomas. Patients are often young at presentation, with the condition having a male predominance.

Predisposing Factors

The exact cause of ALCL is unknown; however, the following factors are known:

  • There is a male predominance;
  • A 2;5 translocation is present in most patients with the primary systemic subtype of ALCL. Overexpression of the anaplastic lymphatic kinase (ALK) protein confirms the diagnosis.

Macroscopic Features

Due to lymphatic tissue being found in many parts of the body – e.g. lymph nodes, lymph vessels, spleen, thymus, bone marrow – non-Hodgkin’s lymphoma can essentially begin anywhere in the body. When ALCL involves the lymph nodes, it can either involve the whole lymph node in a widespread manner, or it can involve just the outer edge and sinusoids (small passages for blood).

Microscopic Features


On histological examination, as seen to the right, the cells in ALCL are large with abundant cytoplasm. The nucleus is horseshoe-shaped, with prominent centres. The tumour cells may be multinucleated. Many of these abnormalities can be seen in the accompanying image.
Under specific immunological investigation, the tumour cells show a substance/antigen called CD30 or Ki-1 on the cell surface.

Natural History

The disease is rapidly progressive. Approximately half of the patients present at Stage I or II, with the remainder presenting at an advanced stage.

Staging

  • Stage I: Involvement of a single lymph node region or lymphatic structure;
  • Stage II: Involvement of 2 or more lymph node regions on the same side of the diaphragm;
  • Stage III: Involvement of lymph node regions or structures on both sides of the diaphragm;
  • Stage IV: Involvement of extra-nodal sites beyond that proximal to the nodal site involved in Stage I-III.

Clinical History

  • The median age of patients is about 34;
  • It is common in children, and about 65% of the patients are male;
  • It usually starts in the lymph nodes, but can also involve the skin and other organs;
  • There are two clinical subtypes: primary and secondary.

The primary subtype can be further divided into systemic, cutaneous, and HIV-related forms, of which the first two are more common.

Primary ALCL (divided into systemic, cutaneous and HIV-related):

  • The primary systemic subtype involves the bone marrow (leading to anaemia, recurrent infections, bleeding), skin, soft tissues (causing muscle aches), bone, lung, liver, gastrointestinal tract (causing diarrhoeanausea, vomiting etc) and, rarely, the central nervous system. Most patients will have fever as a common symptom;
  • The primary cutaneous subtype, as the name suggests, primarily involves the skin. Patients get reddish skin nodules which may form ulcers;
  • The HIV-related form involves B cells, another type of white blood cell which is responsible for producing antibodies.

Secondary:

  • Mainly from other lymphomas e.g. peripheral T cell lymphoma, mycosis fungoides etc.;
  • Normally, it does not express the protein ALK, and thus the disease outcome is worse;
  • Often in older patients.

A majority of patients have either primary systemic or primary cutaneous ALCL. B symptoms (fever, weight loss, night sweats) are present in more than half of the cases. Some patients have only one particular part of their body involved e.g. the bone or muscle.

Clinical Examination

The doctor will examine the patient focusing on lymph node enlargement, organ enlargement (e.g. the spleen, liver), presence of skin nodules or ulcers, and B symptoms (fever, weight loss).

General Investigation

  • Full blood picture, peripheral smear;
  • Urine and electrolytes, liver function tests, renal function tests.

Specific Investigations

  • Chest X-rays and CT scans of the chest, abdomen and pelvis will be performed;
  • In some cases, an ultrasound, bone marrow aspiration (taking a sample from the bone marrow), bone scan and MRI will be needed;
  • To confirm the diagnosis of ALCL, a biopsy of the lymph node is necessary. A small amount of tissue (cluster of cells) is taken from the lymph nodes, usually under anaesthesia, to be looked under the microscope for the cell characteristics;
  • For the purpose of predicting the disease outcome, the levels of a few substances in the blood may be useful: serum lactic dehydrogenase (LDH), beta2-microglobulin and albumin levels. These are done through blood tests.

Prognosis

The survival rate is high, with it being the best among those of all the aggressive lymphomas. The 5-year survival rate is more than 70%. The ALK oncogene is an important prognostic factor – overexpression carries a better treatment outcome. The secondary ALCL tends to be ALK-negative and thus carries a poorer prognosis.

References

  1. What is non-Hodgkin’s lymphoma? [online]. New York, NY: American Cancer Society; 2004 [cited 29 July 2005]. Available from: URL link
  2. Braunwald E, Fauci AS, Kasper DL, et al. Harrison’s Principles of Internal Medicine (15th edition). New York: McGraw-Hill Publishing; 2001. [Book]
  3. Krishnan K, Urbanski C. Lymphoma, malignant anaplastic (Ki 1+) [online]. Omaha, NE: eMedicine; 2004 [cited 29 July 2005]. Available from: URL link