Anaplastic large cell lymphoma

December 31, 2014

Synonyms

Overview

Anaplastic large cell lymphoma is a rare type of non-Hodgkin lymphoma. It is made up of either malignant T-cells (type of cells in the immune system), or 'Null-lymphocytes' (lack both B or T-cell markers).

It is described in detail in the "Classification of Tumors of the Hematopoietic and Lymphoid Tissues" edited by experts of the World Health Organisation. The term anaplastic large cell lymphoma encompasses at least 4 different clinical entities, all sharing the same name, and histologically have also in common the presence of large pleomorphic cells that express CD30 and T-cell markers. Two types of ALCL present as systemic disease and are considered as aggressive lymphomas, while two types present as localized disease and may progress locally. Its name derives from anaplasia and large-cell lymphoma.

It is accounting for about one in 50 of all cases. It can occur at any time between childhood and old age, but is most common in children and young adults. It is about twice as common in men as in women.

Symptoms

Patients usually present with solitary or ulcerating nodules or tumors (Enlarged lymph nodes in multiple regions of the body, or with tumors outside the lymph nodes (extranodal) such as bone, intestine, muscle, liver, or spleen)
Lesions are typically reddish brown and indurated
Involvement of the draining regional lymph nodes occurs in approximately 25% of patients (This does not appear to be associated with a worse prognosis)
Weight loss
Fevers and night sweats

Causes

The causes are unknown. It is not due to infection and cannot be passed on to others.

Diagnosis

The diagnosis of ALCL requires the examination by a pathologist of any enlarged lymph node, or any affected extranodal tissue where there the tumor is found, such as the intestine, the liver or bone in the case of systemic ALCL. For the case of cutaneous ALCL, a skin excision is recommended, and for the diagnosis of ALCL associated with breast implants, a cytologic specimen of the effusion around the breast implant or complete examination of the breast capsule surrounding the implant is required.

To make this diagnosis under its present system of classification, the WHO emphasizes the identification of "hallmark" cells and immunopositivity for CD30. Integration of this information with clinical presentation is crucial for final classification and management of patients.

The classification acknowledges the recognition of large cells with pleomorphic nuclei and abundant cytoplasm. The morphologic features require to complement with immunophenotypic evidence that cells are T lymphocytes, such as the expression of immunologic markers CD3 or CD4, but always it is required the expression of CD30 in all neoplastic cells. Out of the 4 types of ALCL, one subtype of systemic ALCL expresses the protein anaplastic lymphoma kinase (ALK), and the other types of ALCL do not express ALK.

The hallmark cells are of medium size and feature abundant cytoplasm (which may be clear, amphophilic or eosinophilic), kidney shaped nuclei, and a paranuclear eosinophilic region. Occasional cells may be identified in which the plane of section passes through the nucleus in such a way that it appears to enclose a region of cytoplasm within a ring; such cells are called "doughnut" cells.

By definition, on histological examination, hallmark cells are always present. Where they are not present in large numbers, they are usually located around blood vessels. Morphologic variants include the following types:

Common (featuring a predominance of hallmark cells)
Small-cell (featuring smaller cells with the same immunophenotype as the hallmark cells)
Lymphohistiocytic
Sarcomatoid
Signet ring

Prognosis

The prognosis varies according with the type of ALCL. During treatment, relapses may occur but these typically remain sensitive to chemotherapy.

Those with ALK positivity have better prognosis than ALK negative ALCL. It has been suggested that ALK-negative anaplastic large-cell lymphomas derive from other T-cell lymphomas that are morphologic mimics of ALCL in a final common pathway of disease progression. Whereas ALK-positive ALCLs are molecularly characterized and can be readily diagnosed, specific immunophenotypic or genetic features to define ALK-negative ALCL are missing and their distinction from other T-cell non-Hodgkin lymphomas (T-NHLs) remains controversial, although promising diagnostic tools for their recognition have been developed and might be helpful to drive appropriate therapeutic protocols.

Systemic ALK+ ALCL 5-year survival: 70–80%. Systemic ALK- ALCL 5-year survival: 15–45%. Primary Cutaneous ALCL: Prognosis is good if there is not extensive involvement regardless of whether or not ALK is positive with an approximately 90% 5-year survival rate. Breast implant-associated ALCL has an excellent prognosis when the lymphoma is confined to the fluid or to the capsule surrounding the breast implant. This tumor can be recurrent and grow as a mass around the implant capsule or can extend to regional lymph nodes if not properly treated.

Treatment

Systemic ALCL is treated with the chemotherapy regimen CHOP (cyclophosphamide, doxorubin, vincristine and prednisolone). Other therapies include radiotherapy, stem cell transplants and steroid therapy. People with ALK-positive ALCL generally respond well to chemotherapy. Primary cutaneous ALCL may go into spontaneous remission (the disease goes away without treatment). However this is inevitably followed by a relapse. If no spontaneous remission occurs, or if the lymphoma relapses, the most common treatments for this type of ALCL include radiation therapy and/or surgery to remove the affected area of skin. When there is extensive involvement that cannot be treated with these localised therapies, systemic chemotherapy may be required.

Approved therapy:
Brentuximub Vedotin (Adcetris) - FDA-approved indication: The treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen