dermatology - ponzoni

• The skin being the primary site for tumors is equipped with various cells.
• Lymphocytes in the skin can degenerate and become neoplastic, leading to lymphomas.
• Lymphomas can originate from lymph nodes and extranodal sites, including the skin.
• Primary cutaneous lymphoproliferative disorders have different natural histories, prognoses, and implications based on their classification.

Pros and Cons of New Classifications

• New classifications offer better-reshaped entities and recognition of new entities.
• New classifications introduce different nomenclatures and concepts.
• Differing classifications can hinder large-scale comparative studies (e.g., drug efficacy).
• New classifications might not be universally applicable for molecular evaluations.
• New classifications can be challenging for patients and clinicians, beyond pathologists.

Classification Systems

• There are two main classification systems in use today.
• WHO5 is used globally, published as a preview with an online version, but the Blue books are not yet available.
• ICC is published in a definitive format and includes a major revision of plasma cell neoplasms.
• Provisional entities are now translated into a definitive entity in WHO5 classification.
• Transformation of indolent B cell lymphomas is introduced as an entity.
• Diagnostic criteria are subdivided into essential and desirable criteria.
• San Raffaele hospital specifies each tumor according to both classifications.

Types of Lymphoproliferations

• Two types of lymphoproliferations occur in the skin: T cell and B cell disorders.
• Clinicopathological correlations are essential for skin disorders, linking microscopic observations with dermatological examinations.
• Skin disorders are heterogeneous with no clear correlation between lymphoma type and microscopy, but each lymphoma type has specific abnormalities.
• Useful markers include CD3, CD2, CD7, and CD5, in addition to CD4 and CD8.
• CD4 and CD8 markers are often mutually exclusive and alternatively expressed.
• Functional markers relate to cytotoxic granules, important for natural immunity, leaking from T cells to attack target cells.
• Cytotoxic lymphocytes may undergo neoplastic transformation, and granzyme B, perforin, and TIA1 are useful staining markers.
• Antigen loss, where T cells express only a portion of molecules (e.g., CD3 but not CD2/CD7), can occur.
• Antigen loss can be linked to autoimmune disorders such as pemphigus, impetigo, lichen planus and SLE.

Cutaneous T-Cell Lymphomas

• Major T cell cutaneous lymphoproliferative disorders are classified into five classes.
• Mycosis fungoides, anaplastic large cell lymphoma, and panniculitis-like T cell lymphoma are the most frequent.
• Indolent lymphomas can take years to develop, while aggressive lymphomas take only a few months.

CD8 Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma

• Affected patients have a survival rate of only a few weeks, even with treatment.
• This tumor is epidermotropic, with neoplastic lymphocytes attacking the epidermis, causing ulceration of the skin.
• Lymphocytes are medium to large, with a proliferation index (Ki67) of 70%.
• Stainings include CD3, CD8, and TIA1, with TIA1 staining cytotoxic granules.

CD4+ Small/Medium T-Cell Lymphoproliferative Disorders

• Lymphoproliferative disorders feature a tumor but are not fully malignant.
• These disorders are indolent, self-limited, and localized, but may disseminate if untreated.
• Lesions typically affect the head and neck region, presenting as a single lesion.
• There is a separation zone between the epidermis and the involved dermis referred to as the Grenz zone.
• The population is polymorphic and heterogeneous.
• Cells are medium-sized, with few mitotic figures (Ki67 is <5%).
• Immunohistochemistry shows cells positive for CD3 and CD4.