Primary cutaneous anaplastic large cell lymphoma

by Jason Wasserman MD PhD FRCPC and Aleksandra Paliga MD FRCPC
December 16, 2024

This article is designed to help you understand your pathology report for primary cutaneous anaplastic large cell lymphoma. Each section explains an important aspect of the diagnosis and what it means for you.

What is primary cutaneous anaplastic large cell lymphoma?

Primary cutaneous anaplastic large cell lymphoma is a type of cancer that develops in the skin and belongs to a group of conditions called primary cutaneous CD30-positive T-cell lymphoproliferative disorders. It is made up of large cancer cells with an irregular, or anaplastic, appearance under the microscope. More than 75% of these cancer cells express a marker called CD30, which helps doctors identify the disease.

A lymphoma is a type of cancer that arises from white blood cells. In primary cutaneous anaplastic large cell lymphoma, the cancer cells originate from T cells, a type of white blood cell that normally plays a role in the immune system.

What are the symptoms of primary cutaneous anaplastic large cell lymphoma?

Primary cutaneous anaplastic large cell lymphoma usually presents as a tumour involving the skin, though less commonly, it can affect a mucous membrane, such as the lining of the mouth. The tumour often appears as a firm, raised red or purple lump that can vary in size. The surface of the tumour may break open and form an ulcer, causing discomfort or pain.

In most cases, the cancer involves a single tumour, but in about 20% of cases, people may develop multiple tumours in different areas of the skin. These additional tumours may appear at the same time or over weeks to months.

What causes primary cutaneous anaplastic large cell lymphoma?

The exact cause of this type of cancer is not well understood. Scientists believe it develops when genetic changes occur in T cells, a type of white blood cell responsible for regulating the immune system. These changes allow the cells to grow uncontrollably, forming cancer in the skin.

How is this diagnosis made?

The diagnosis begins with a thorough medical history and physical examination. If cancer is suspected, a small sample of the affected skin, called a biopsy, is taken and examined under a microscope by a pathologist. Additional tests, such as immunohistochemistry and genetic studies, may be performed on the biopsy sample to confirm the diagnosis.

It is important to note that primary cutaneous anaplastic large cell lymphoma is a clinical and pathologic diagnosis. In many instances, the pathologist will sign out a case as “primary cutaneous CD30-positive T-cell lymphoproliferative disorder” and provide a differential diagnosis of lymphomatoid granulomatosis, CD30-positive advanced mycosis fungoides, and cutaneous anaplastic large cell lymphoma versus peripheral anaplastic large cell lymphoma or another CD30 positive T cell lymphoma involving the skin. This long list of potential conditions is necessary because reaching a diagnosis through pathologic examination alone is often impossible. Additional imaging and clinical information about tumour progression is needed to establish a final diagnosis.

Microscopic features of this tumour

When pathologists examine the affected tissue under a microscope, they see large cancer cells with distinct features:

• The cancer cells often have large, irregularly shaped nuclei (the part of the cell that contains genetic material), prominent nucleoli (small structures inside the nucleus), and abundant cytoplasm (the substance surrounding the nucleus).
• These cancer cells usually form dense clusters or diffuse sheets in the skin or mucous membranes.
• In rare cases, the cancer cells are found in blood vessels or lymphatic channels (intravascular lymphoma).

Immunohistochemistry

Immunohistochemistry is a test that uses special stains to detect proteins in cancer cells. It helps pathologists identify the type of cancer and its unique features. In primary cutaneous anaplastic large cell lymphoma:

• The cancer cells typically have markers seen in activated T cells, such as CD4, but may lose markers like CD2, CD3, CD5, or CD7.
• More than 75% of the cancer cells are positive for CD30, a hallmark of this type of cancer.
• Some cancer cells also produce proteins associated with cytotoxic T cells, like TIA1 or granzyme B.
• Rarely, the cancer cells express other markers, like CD56 or CD8, but these findings do not usually affect the prognosis.

How is primary cutaneous anaplastic large cell lymphoma staged?

The pathologic staging of primary cutaneous anaplastic large cell lymphoma describes how far the cancer has spread in the skin and whether the cells have spread to lymph nodes or other parts of the body. This staging system guides doctors in planning the most effective treatment.

T stage: Skin involvement

• T1: A single lesion is present.
  • T1a: The lesion is smaller than 5 cm across.
  • T1b: The lesion is larger than 5 cm across.
• T2: Multiple lesions are found in one area or two connected regions of the body.
  • T2a: The lesions fit within a 15-cm circle.
  • T2b: The lesions fit within a 15 to 30-cm circle.
  • T2c: The lesions fit within a circle larger than 30 cm.
• T3: The lesions are widespread across the body.
  • T3a: Two non-connected areas of the body are involved.
  • T3b: Three or more body areas are involved.

N stage: Lymph node involvement

• N0: No lymph node involvement.
• N1: One lymph node group that drains an affected skin area is involved.
• N2: Two or more lymph node groups or lymph nodes not draining the affected area are involved.
• N3: The cancer has spread to central lymph nodes (such as those deep within the body).

This staging system helps doctors assess the extent of the disease and select the most appropriate treatment. Local therapies like radiation may be sufficient for early-stage cases, while advanced stages may require more intensive treatments.

Prognosis

The prognosis for primary cutaneous anaplastic large cell lymphoma is generally very good. About 90% of people are alive 10 years after their diagnosis, and the disease often remains limited to the skin. Even when the cancer spreads to nearby lymph nodes, it does not usually affect the overall outlook.

However, the prognosis may be less favourable in certain situations, such as:

• Extensive skin involvement, especially on the legs.
• Being over the age of 60 at the time of diagnosis.

Doctors use these factors and test results to develop a personalized treatment plan.