119: Cutaneous Lymphoma Flashcards
What are primary cutaneous lymphomas?
Primary cutaneous lymphomas are a heterogeneous group of extranodal non-Hodgkin lymphomas that arise from malignant clonal transformation of skin homing or resident T cells or B lymphocytes.
How do primary cutaneous lymphomas differ from nodal non-Hodgkin lymphomas?
They are defined entities with distinct clinical behavior and prognosis, requiring different treatment approaches compared to nodal non-Hodgkin lymphomas.
What is the incidence trend of cutaneous T-cell lymphomas (CTCLs) in the United States?
The incidence of CTCLs has increased significantly, with reports of 6.4 cases per million people between 1993 and 2002, and 7.7 cases per million people between 2001 and 2005.
What is the median age at diagnosis for cutaneous T-cell lymphomas (CTCLs)?
The median age at diagnosis is in the mid-50s, with a fourfold increase in incidence for individuals over 70 years of age.
What are the two main forms of cutaneous T-cell lymphoma (CTCL) and their prevalence?
The two most common forms of CTCL are Mycosis Fungoides (MF) and Sézary syndrome, which together account for 65% of CTCL cases.
What are the second most common forms of cutaneous T-cell lymphoma (CTCL)?
The second most common forms (27%) include primary cutaneous CD30+ lymphoproliferative disorders such as lymphomatoid papulosis and cutaneous anaplastic large-cell lymphoma.
What are the distinct populations of T cells involved in primary cutaneous T-cell lymphoma?
There are four functionally distinct populations of T cells involved: 1. Central memory T cells (T_CM) 2. Effector memory T cells (T_EM) 3. Tissue-resident memory T cells (T_RM) 4. Migratory memory T cells (T_MM).
What endogenous factors are associated with Mycosis Fungoides (MF) and Sézary syndrome?
Distinct HLA class II molecules, specifically HLA-DRB111 and DQB103, are significantly overrepresented in patients with Mycosis Fungoides and Sézary syndrome.
What exogenous factors are implicated in cutaneous lymphomas?
Viruses are considered etiologic factors in at least two cutaneous lymphomas, specifically Mycosis Fungoides (MF) and Sézary syndrome.
What does a T-cell clone derived from tissue-resident memory cells (TRM) indicate about Mycosis Fungoides?
It indicates a tendency of Mycosis Fungoides to form stable inflammatory skin lesions.
What role does Epstein-Barr virus (EBV) play in cutaneous T-cell lymphomas (CTCLs)?
EBV is associated with CD30 lymphoproliferation and immunosuppression, which is related to a poor prognosis.
How do bacterial infections, specifically Staphylococcus aureus, influence cutaneous T-cell lymphoma (CTCL)?
Staphylococcus aureus can cause chronic antigenic stimulation in CTCL patients, leading to disease exacerbation.
What are the common environmental and occupational risk factors associated with Mycosis Fungoides (MF)?
Common risk factors include exposure to carcinogens in the work environment, particularly for glass formers, potters, and paper and wood industry workers.
What are the key components shared by clinical entities encompassed by cutaneous T-cell lymphoma?
The key components include: 1. The epidermal and/or dermal microenvironment 2. A clonal T-cell population 3. A modulated antitumor response.
What distinguishes malignant T cells in Mycosis Fungoides (MF) from those in Sézary syndrome?
Malignant T cells in MF have the surface phenotype of nonrecirculating T RM, while Sézary syndrome T cells have a surface phenotype of T CM.
What is the significance of high-throughput TCR sequencing in the diagnosis of cutaneous T-cell lymphoma (CTCL)?
High-throughput TCR sequencing allows for the discrimination of malignant T-cell clones from benign inflammatory skin diseases.
What is the suspected role of occupational exposure to carcinogens in Mycosis Fungoides?
Carcinogens in the work environment are suspected to provide long-term antigenic stimulation, initiating clonal expansion of malignant T cells.
What are the molecular pathogenesis factors associated with Cutaneous T-Cell Lymphoma (CTCL)?
- Recurrent deletions of 10q and 17p
- Deletions of TP53 and CDKN2a
- Amplification of 8q and 17q, including MYC
- Somatic mutations in 17 genes in CTCL
- Frequent deletion and damaging somatic copy number variants in chromatin-modifying genes
- Mutations in TCR signaling pathway components.
How do cytokines influence the progression of Cutaneous T-Cell Lymphoma (CTCL)?
- Cytokines IL-2, IL-7, and IL-15 activate JAK1/JAK3, leading to the activation of STAT5 and STAT3.
- STAT5 activates IL-4 expression, fostering Th2 phenotype.
- Th2 responses are mechanisms of tumor-induced immunosuppression.
- Activation of STAT3 promotes survival of malignant T cells.
What is the significance of miRNA-21 in the context of Cutaneous T-Cell Lymphoma (CTCL)?
- miRNA-21 is involved in the survival of malignant T cells due to its antiapoptotic activities.
- Its expression is induced by STAT3 transcriptional activity.
What are the clinical findings associated with Mycosis Fungoides (MF)?
- MF is categorized as patch, plaque, or tumor stage.
- Patients may have multiple types of lesions simultaneously.
What is the definition and demographic information regarding Mycosis Fungoides (MF)?
- Mycosis Fungoides is the most common form of primary cutaneous lymphoma, accounting for approximately 40% of all cutaneous lymphomas.
- It typically arises in mid to late adulthood, with a median age at diagnosis of 55-60 years.
What is the most likely diagnosis for a 55-year-old patient with erythematous, scaly macules and patches?
The most likely diagnosis is Mycosis Fungoides (MF), specifically in the early patch stage.
What are the characteristics of the patch stage in Mycosis Fungoides?
The patch stage is characterized by sharply demarcated, scaly, elevated lesions that may regress spontaneously or coalesce.
What are the symptoms associated with erythrodermic Mycosis Fungoides?
Symptoms include involvement of 80% of body surface area, bright red appearance, and characteristic islands of uninvolved skin.
What histopathological features are observed in Mycosis Fungoides?
Histopathological features include band-like infiltrate in the upper dermis and hyperconvoluted cerebriform nuclei.
How does hypopigmented Mycosis Fungoides present in darker-skinned individuals?
Hypopigmented Mycosis Fungoides presents as lesions that develop in patients with dark skin and often responds to therapy with repigmentation.
What are the common symptoms experienced by patients with Mycosis Fungoides?
Common symptoms include fever, chills, weight loss, malaise, insomnia, and intense pruritus.
What does the reappearance of hypopigmented lesions indicate in Mycosis Fungoides?
The reappearance of hypopigmented lesions often indicates a relapse of Mycosis Fungoides.
What stage is characterized by sharply demarcated, scaly, elevated lesions in Mycosis Fungoides?
This is the plaque stage of Mycosis Fungoides.
What diagnostic approach should be taken for early-stage Mycosis Fungoides?
Multiple biopsy specimens should be taken to pursue a diagnosis.
What stage is indicated by nodules that ulcerate and become secondarily infected in Mycosis Fungoides?
This is the tumor stage of Mycosis Fungoides, indicating a more aggressive form of the disease.
What does the ‘deck chair’ sign indicate in erythrodermic Mycosis Fungoides?
The ‘deck chair’ sign indicates sparing of folded skin areas.
What histological finding is associated with intraepidermal Pautrier microabscesses in Mycosis Fungoides?
Intraepidermal Pautrier microabscesses are associated with the patch, plaque, and erythrodermic stages.
What histological feature characterizes neoplastic T cells in Mycosis Fungoides?
The neoplastic T cells are characterized by hyperconvoluted cerebriform nuclei.
What does partial loss of pan–T-cell antigens such as CD7 and CD3 indicate in Mycosis Fungoides?
Partial loss of pan–T-cell antigens may be a feature of Mycosis Fungoides but is not pathognomonic.
What does a T-cell clone found in only half the biopsies imply about early-stage Mycosis Fungoides?
Molecular tests for T-cell clonality are not of significant diagnostic value in early stages.
What is the role of TOX in the diagnosis of Mycosis Fungoides and Sézary syndrome?
TOX helps in distinguishing early MF lesions from inflammatory skin disorders and contributes to the diagnosis of CTCL.
What are the key factors influencing the prognosis of Mycosis Fungoides?
The prognosis depends on type and extent of skin involvement, presence of lymph node involvement, and visceral disease.
What are the survival rates for patients with different stages of Mycosis Fungoides?
Median overall survival was 63 months with 2-year and 5-year survival rates of 77% and 52%, respectively.
What treatment options are available for early-stage Mycosis Fungoides?
Treatment may include skin-directed therapies alone or combined with systemic biologic response modifiers.
What is the median overall survival for patients with Stage IIB disease?
The median overall survival for patients with Stage IIB disease was 86 months.
How does Stage III disease survival compare to Stage IIB disease?
Stage III disease has slightly improved survival compared to Stage IIB disease.
What is the survival rate for Stage IV disease?
Stage IV disease had significantly worse survival: 48 months for Stage IVA and 33 months for Stage IVB.
What treatment options are available for early-stage Mycosis Fungoides?
Treatment for early-stage Mycosis Fungoides may include skin-directed therapies alone or combined with systemic biologic response modifiers (e.g., interferon α or γ, retinoids) and targeted therapies.
What is the 5-year survival rate for a patient with early-stage Mycosis Fungoides?
A patient with Mycosis Fungoides has a 5-year survival rate of 80%-100%.
What stage is a patient likely in if they have a 5-year survival rate of 40%?
The patient is likely in an advanced stage with lymph node involvement.
What is the median overall survival for a patient with Sézary Syndrome?
A patient with Sézary Syndrome has a median overall survival of 33 months.
What are the characteristics of Folliculotropic MF?
Folliculotropic MF is characterized by folliculotropic T-cell infiltrates, predominantly affects adults, and presents with patches, plaques, and unusual hair loss.
What is the prognosis for Folliculotropic MF?
5-year survival rates are approximately 60% for follicular MF and 41% for folliculotropic MF by 15 years.
What are the clinical findings associated with Sézary Syndrome?
Clinical findings include diffuse erythroderma, generalized lymphadenopathy, and circulating malignant T cells with cerebriform nuclei.
What laboratory findings are typical for Sézary Syndrome?
Laboratory findings include histologic features similar to Mycosis Fungoides, clonal T cells generally CD3+, CD4+, and CD8−, and loss of CD7 expression in 2/3 of cases.
What is Granulomatous Slack Skin?
Granulomatous Slack Skin is a rare condition characterized by localized areas of bulky folding of skin, primarily affecting the axillae and groin.
What is the prognosis for Granulomatous Slack Skin?
The prognosis is generally poor, with neoplastic cells expressing a CD3+CD4+CD8− phenotype.
What are the clinical findings of Lymphomatoid Papulosis?
Clinical findings include chronic, recurrent, and self-healing papulonecrotic or papulonodular skin eruptions.
What histopathological features are seen in Lymphomatoid Papulosis?
Atypical cells express one or more T-cell antigens and the lymphoid activation antigen CD30.
What does a CD4-to-CD8 ratio of more than 10 indicate in Sézary Syndrome?
An expanded CD4+ T-cell population resulting in a CD4-to-CD8 ratio of more than 10 is a diagnostic criterion for Sézary Syndrome.
What is the primary cause of mortality in Sézary Syndrome?
The primary cause of mortality in Sézary Syndrome is infectious complications due to very little normal immunity left.
What is the diagnosis for a patient with diffuse erythroderma and circulating malignant T cells?
The diagnosis is Sézary Syndrome, with an unfavorable prognosis and a 5-year overall survival rate of 24% to 43%.
What does loss of CD7 and CD26 expression indicate in Sézary Syndrome?
Loss of CD7 and CD26 expression is frequently observed in Sézary Syndrome and is useful in identifying Sézary cells.
What is the prognosis for Folliculotropic Mycosis Fungoides?
Folliculotropic Mycosis Fungoides has a worse prognosis, with 5-year survival rates of approximately 41%.
What distinguishes Pagetoid Reticulosis from classic Mycosis Fungoides?
Pagetoid Reticulosis is distinguished by its solitary lesion, more prominent epidermotropism, and lack of extracutaneous dissemination.
What histological findings support a diagnosis of granulomatous slack skin?
Histology shows a dense granulomatous infiltrate in the dermis, macrophages, multinucleated giant cells, and loss of elastic fibers.
What is the significance of aberrant expression of CD158k/KIR3DL2 in Sézary Syndrome?
Aberrant expression of CD158k/KIR3DL2 is a useful marker for identifying Sézary cells.
What is the prognosis for primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma?
The prognosis is generally favorable with a 10-year survival rate of nearly 100%, but monitoring is required.
What are the treatment options for solitary or localized skin lesions in Cutaneous Anaplastic Large-Cell Lymphoma?
The treatment of choice is excision or radiotherapy, with other options including PUVA in combination with interferon-α.
What is the most common phenotype observed in Cutaneous Anaplastic Large-Cell Lymphoma?
The most common phenotype observed is CD4+ T-helper phenotype.
What are the clinical findings associated with Subcutaneous Panniculitis-Like T-Cell Lymphoma?
Clinical findings include subcutaneous nodules and plaques, predominantly affecting the legs and trunk.
What is the significance of TCR rearrangement in lymphomatoid papulosis?
Monoclonal TCR rearrangement may be prognostic for disease more likely to develop lymphomatoid papulosis-associated lymphomas.
What is the long-term management strategy for lymphomatoid papulosis?
Long-term follow-up without active treatment is recommended for patients with few, nonscarring lesions.
What is the treatment of choice for localized lesions in primary cutaneous anaplastic large-cell lymphoma?
Excision or radiotherapy is the treatment of choice for solitary or localized skin lesions.
What chromosomal rearrangement is associated with lymphomatoid papulosis?
The IRF4/DUSP locus on chromosome 6p25 is associated with this variant of lymphomatoid papulosis.
What does a tumor expressing CD30 but lacking ALK indicate?
This indicates that primary cutaneous anaplastic large-cell lymphomas are usually negative for ALK.
What are the histopathological features of subcutaneous infiltrates in T-cell lymphoma?
Features include a mixture of neoplastic pleomorphic cells and rimming of individual fat cells by neoplastic T cells.
What is the prognosis for α/β type of subcutaneous panniculitis-like T-cell lymphoma?
The α/β type responds well to systemic corticosteroids, leading to an excellent prognosis with a 5-year survival rate of 85%.
What are the clinical findings associated with Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type?
Clinical findings include destruction of the nasal region and skin lesions such as subcutaneous tumors and ulcers.
What are the histopathological characteristics of Primary Cutaneous Aggressive Epidermotropic CD8+ Cytotoxic T-Cell Lymphoma?
Characteristics include band-like infiltrates and high frequency of Ki67 antigen expression.
What is the prognosis for Primary Cutaneous Aggressive Epidermotropic CD8+ Cytotoxic T-Cell Lymphoma?
Even with multiagent chemotherapy, the course is aggressive with a median survival of approximately 32 months.
What defines Cutaneous γ/δ T-Cell Lymphoma?
It comprises peripheral T-cell lymphomas with a clonal proliferation of mature, activated γ/δ T cells.
What is the initial treatment approach for subcutaneous panniculitis-like T-cell lymphoma?
Systemic corticosteroids are the initial treatment approach for the α/β type.
What is the typical prognosis for extranodal NK/T-cell lymphoma, nasal type?
The prognosis is poor, as this aggressive disease is often lethal within months.
What is the median survival for primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma?
The median survival for this aggressive lymphoma is 32 months.
What does expression of βF1 indicate in subcutaneous panniculitis-like T-cell lymphoma?
Expression of βF1 indicates a TCR α/β phenotype.
What does the presence of EBV in tumor cells indicate in extranodal NK/T-cell lymphoma?
It indicates a viral association characteristic of extranodal NK/T-cell lymphoma, nasal type.
What is unusual about the metastasis pattern in primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma?
Metastatic spread to unusual sites like the CNS is common, but lymph node involvement is not typically observed.
What are the three major patterns of involvement in histopathology for cutaneous lymphomas?
The three major patterns are epidermotropic, dermal, and subcutaneous.
What is the prognosis for patients with Primary Cutaneous Acral CD8+ T-Cell Lymphoproliferation?
The prognosis is favorable.
What are the clinical features of indolent cutaneous, CD8+ lymphoid proliferation?
Features include solitary skin lesions on the face or acral sites.
What is the median survival for aggressive disease resistant to multiagent chemotherapy?
Median survival is 15 months.
What is a new discriminative marker for indolent CD8+ lymphoid proliferation?
CD68 could be a new discriminative marker.
What is the typical prognosis for cutaneous γ/δ T-cell lymphoma?
The prognosis is poor, with a median survival of 15 months.
What is the prognosis for primary cutaneous acral CD8+ T-cell lymphoproliferation?
The prognosis is excellent, with complete remission lasting for years.
What does strong positivity for TCR δ indicate in cutaneous γ/δ T-cell lymphoma?
It indicates a γ/δ origin of the lymphoma.
What marker can help distinguish indolent CD8+ lymphoid proliferation from other CD8+ cutaneous lymphomas?
CD68- could be a discriminative marker.
What are the key signaling pathways involved in cutaneous T-cell lymphoma?
Key pathways include JAK-STAT, NF-κB, TCR, Apoptosis, Cell Cycle, Genome Integrity, and Cytoskeletal Dynamics.
What is the role of epigenetic regulators in cutaneous T-cell lymphoma?
Epigenetic regulators influence gene expression without altering the DNA sequence.
What are the key regulators involved in apoptosis?
FAS and TNFRSF10A pathways trigger apoptotic signals.
These pathways are crucial in cutaneous T-cell lymphoma.
What role do epigenetic regulators play in cutaneous T-cell lymphoma?
Epigenetic regulators influence gene expression without altering the DNA sequence.
Key regulators include ARID1A (chromatin remodeling), DNMT3A (DNA methylation), and KMT2C (histone modification).
What is the function of ARID1A?
Chromatin remodeling.
ARID1A is a key epigenetic regulator in cutaneous T-cell lymphoma.
What is the function of DNMT3A?
DNA methylation.
DNMT3A is a key epigenetic regulator in cutaneous T-cell lymphoma.
What is the function of KMT2C?
Histone modification.
KMT2C is a key epigenetic regulator in cutaneous T-cell lymphoma.
How does the JAK-STAT pathway affect T-cells?
JAK-STAT pathway activation can lead to cell survival or apoptosis depending on the context.
This pathway’s role is crucial in the fate of T-cells in cutaneous T-cell lymphoma.
What role does NF-κB signaling play in T-cell survival?
NF-κB signaling can promote cell survival, counteracting apoptotic signals.
The balance between NF-κB and apoptotic signals determines T-cell fate in lymphoma.
What is the significance of the balance between apoptotic and survival pathways?
The balance determines the fate of T-cells in the lymphoma context.
This balance is crucial for understanding cutaneous T-cell lymphoma progression.
What are the main components of the cell cycle regulation?
Key regulators include Rb, p16, and CDKN2A.
These components are important in cell cycle control.
What is the role of TP53 and ATM in genome integrity?
TP53 and ATM are critical for maintaining genome integrity.
They help in DNA damage response and repair mechanisms.
What are the key players in cytoskeletal dynamics?
Key players include RhoA, ERK, and AKT.
These molecules are involved in regulating cytoskeletal structure and function.
