119: Cutaneous Lymphoma

Question 1

What are primary cutaneous lymphomas?

Answer 1

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.

Question 2

How do primary cutaneous lymphomas differ from nodal non-Hodgkin lymphomas?

Answer 2

They are defined entities with distinct clinical behavior and prognosis, requiring different treatment approaches compared to nodal non-Hodgkin lymphomas.

Question 3

What is the incidence trend of cutaneous T-cell lymphomas (CTCLs) in the United States?

Answer 3

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.

Question 4

What is the median age at diagnosis for cutaneous T-cell lymphomas (CTCLs)?

Answer 4

The median age at diagnosis is in the mid-50s, with a fourfold increase in incidence for individuals over 70 years of age.

Question 5

What are the two main forms of cutaneous T-cell lymphoma (CTCL) and their prevalence?

Answer 5

The two most common forms of CTCL are Mycosis Fungoides (MF) and Sézary syndrome, which together account for 65% of CTCL cases.

Question 6

What are the second most common forms of cutaneous T-cell lymphoma (CTCL)?

Answer 6

The second most common forms (27%) include primary cutaneous CD30+ lymphoproliferative disorders such as lymphomatoid papulosis and cutaneous anaplastic large-cell lymphoma.

Question 7

What are the distinct populations of T cells involved in primary cutaneous T-cell lymphoma?

Answer 7

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).

Question 8

What endogenous factors are associated with Mycosis Fungoides (MF) and Sézary syndrome?

Answer 8

Distinct HLA class II molecules, specifically HLA-DRB111 and DQB103, are significantly overrepresented in patients with Mycosis Fungoides and Sézary syndrome.

Question 9

What exogenous factors are implicated in cutaneous lymphomas?

Answer 9

Viruses are considered etiologic factors in at least two cutaneous lymphomas, specifically Mycosis Fungoides (MF) and Sézary syndrome.

Question 10

What does a T-cell clone derived from tissue-resident memory cells (TRM) indicate about Mycosis Fungoides?

Answer 10

It indicates a tendency of Mycosis Fungoides to form stable inflammatory skin lesions.

Question 11

What role does Epstein-Barr virus (EBV) play in cutaneous T-cell lymphomas (CTCLs)?

Answer 11

EBV is associated with CD30 lymphoproliferation and immunosuppression, which is related to a poor prognosis.

Question 12

How do bacterial infections, specifically Staphylococcus aureus, influence cutaneous T-cell lymphoma (CTCL)?

Answer 12

Staphylococcus aureus can cause chronic antigenic stimulation in CTCL patients, leading to disease exacerbation.

Question 13

What are the common environmental and occupational risk factors associated with Mycosis Fungoides (MF)?

Answer 13

Common risk factors include exposure to carcinogens in the work environment, particularly for glass formers, potters, and paper and wood industry workers.

Question 14

What are the key components shared by clinical entities encompassed by cutaneous T-cell lymphoma?

Answer 14

The key components include: 1. The epidermal and/or dermal microenvironment 2. A clonal T-cell population 3. A modulated antitumor response.

Question 15

What distinguishes malignant T cells in Mycosis Fungoides (MF) from those in Sézary syndrome?

Answer 15

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.

Question 16

What is the significance of high-throughput TCR sequencing in the diagnosis of cutaneous T-cell lymphoma (CTCL)?

Answer 16

High-throughput TCR sequencing allows for the discrimination of malignant T-cell clones from benign inflammatory skin diseases.

Question 17

What is the suspected role of occupational exposure to carcinogens in Mycosis Fungoides?

Answer 17

Carcinogens in the work environment are suspected to provide long-term antigenic stimulation, initiating clonal expansion of malignant T cells.

Question 18

What are the molecular pathogenesis factors associated with Cutaneous T-Cell Lymphoma (CTCL)?

Answer 18

• 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.

Question 19

How do cytokines influence the progression of Cutaneous T-Cell Lymphoma (CTCL)?

Answer 19

• 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.

Question 20

What is the significance of miRNA-21 in the context of Cutaneous T-Cell Lymphoma (CTCL)?

Answer 20

• miRNA-21 is involved in the survival of malignant T cells due to its antiapoptotic activities.
• Its expression is induced by STAT3 transcriptional activity.

Question 21

What are the clinical findings associated with Mycosis Fungoides (MF)?

Answer 21

• MF is categorized as patch, plaque, or tumor stage.
• Patients may have multiple types of lesions simultaneously.

Question 22

What is the definition and demographic information regarding Mycosis Fungoides (MF)?

Answer 22

• 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.

Question 23

What is the most likely diagnosis for a 55-year-old patient with erythematous, scaly macules and patches?

Answer 23

The most likely diagnosis is Mycosis Fungoides (MF), specifically in the early patch stage.

Question 24

What are the characteristics of the patch stage in Mycosis Fungoides?

Answer 24

The patch stage is characterized by sharply demarcated, scaly, elevated lesions that may regress spontaneously or coalesce.

Question 25

What are the symptoms associated with erythrodermic Mycosis Fungoides?

Answer 25

Symptoms include involvement of 80% of body surface area, bright red appearance, and characteristic islands of uninvolved skin.

Question 26

What histopathological features are observed in Mycosis Fungoides?

Answer 26

Histopathological features include band-like infiltrate in the upper dermis and hyperconvoluted cerebriform nuclei.

Question 27

How does hypopigmented Mycosis Fungoides present in darker-skinned individuals?

Answer 27

Hypopigmented Mycosis Fungoides presents as lesions that develop in patients with dark skin and often responds to therapy with repigmentation.

Question 28

What are the common symptoms experienced by patients with Mycosis Fungoides?

Answer 28

Common symptoms include fever, chills, weight loss, malaise, insomnia, and intense pruritus.

Question 29

What does the reappearance of hypopigmented lesions indicate in Mycosis Fungoides?

Answer 29

The reappearance of hypopigmented lesions often indicates a relapse of Mycosis Fungoides.

Question 30

What stage is characterized by sharply demarcated, scaly, elevated lesions in Mycosis Fungoides?

Answer 30

This is the plaque stage of Mycosis Fungoides.

Question 31

What diagnostic approach should be taken for early-stage Mycosis Fungoides?

Answer 31

Multiple biopsy specimens should be taken to pursue a diagnosis.

Question 32

What stage is indicated by nodules that ulcerate and become secondarily infected in Mycosis Fungoides?

Answer 32

This is the tumor stage of Mycosis Fungoides, indicating a more aggressive form of the disease.

Question 33

What does the 'deck chair' sign indicate in erythrodermic Mycosis Fungoides?

Answer 33

The 'deck chair' sign indicates sparing of folded skin areas.

Question 34

What histological finding is associated with intraepidermal Pautrier microabscesses in Mycosis Fungoides?

Answer 34

Intraepidermal Pautrier microabscesses are associated with the patch, plaque, and erythrodermic stages.

Question 35

What histological feature characterizes neoplastic T cells in Mycosis Fungoides?

Answer 35

The neoplastic T cells are characterized by hyperconvoluted cerebriform nuclei.

Question 36

What does partial loss of pan–T-cell antigens such as CD7 and CD3 indicate in Mycosis Fungoides?

Answer 36

Partial loss of pan–T-cell antigens may be a feature of Mycosis Fungoides but is not pathognomonic.

Question 37

What does a T-cell clone found in only half the biopsies imply about early-stage Mycosis Fungoides?

Answer 37

Molecular tests for T-cell clonality are not of significant diagnostic value in early stages.

Question 38

What is the role of TOX in the diagnosis of Mycosis Fungoides and Sézary syndrome?

Answer 38

TOX helps in distinguishing early MF lesions from inflammatory skin disorders and contributes to the diagnosis of CTCL.

Question 39

What are the key factors influencing the prognosis of Mycosis Fungoides?

Answer 39

The prognosis depends on type and extent of skin involvement, presence of lymph node involvement, and visceral disease.

Question 40

What are the survival rates for patients with different stages of Mycosis Fungoides?

Answer 40

Median overall survival was 63 months with 2-year and 5-year survival rates of 77% and 52%, respectively.

Question 41

What treatment options are available for early-stage Mycosis Fungoides?

Answer 41

Treatment may include skin-directed therapies alone or combined with systemic biologic response modifiers.

Question 42

What is the median overall survival for patients with Stage IIB disease?

Answer 42

The median overall survival for patients with Stage IIB disease was 86 months.

Question 43

How does Stage III disease survival compare to Stage IIB disease?

Answer 43

Stage III disease has slightly improved survival compared to Stage IIB disease.

Question 44

What is the survival rate for Stage IV disease?

Answer 44

Stage IV disease had significantly worse survival: 48 months for Stage IVA and 33 months for Stage IVB.

Question 45

What treatment options are available for early-stage Mycosis Fungoides?

Answer 45

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.

Question 46

What is the 5-year survival rate for a patient with early-stage Mycosis Fungoides?

Answer 46

A patient with Mycosis Fungoides has a 5-year survival rate of 80%-100%.

Question 47

What stage is a patient likely in if they have a 5-year survival rate of 40%?

Answer 47

The patient is likely in an advanced stage with lymph node involvement.

Question 48

What is the median overall survival for a patient with Sézary Syndrome?

Answer 48

A patient with Sézary Syndrome has a median overall survival of 33 months.

Question 49

What are the characteristics of Folliculotropic MF?

Answer 49

Folliculotropic MF is characterized by folliculotropic T-cell infiltrates, predominantly affects adults, and presents with patches, plaques, and unusual hair loss.

Question 50

What is the prognosis for Folliculotropic MF?

Answer 50

5-year survival rates are approximately 60% for follicular MF and 41% for folliculotropic MF by 15 years.

Question 51

What are the clinical findings associated with Sézary Syndrome?

Answer 51

Clinical findings include diffuse erythroderma, generalized lymphadenopathy, and circulating malignant T cells with cerebriform nuclei.

Question 52

What laboratory findings are typical for Sézary Syndrome?

Answer 52

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.

Question 53

What is Granulomatous Slack Skin?

Answer 53

Granulomatous Slack Skin is a rare condition characterized by localized areas of bulky folding of skin, primarily affecting the axillae and groin.

Question 54

What is the prognosis for Granulomatous Slack Skin?

Answer 54

The prognosis is generally poor, with neoplastic cells expressing a CD3+CD4+CD8− phenotype.

Question 55

What are the clinical findings of Lymphomatoid Papulosis?

Answer 55

Clinical findings include chronic, recurrent, and self-healing papulonecrotic or papulonodular skin eruptions.

Question 56

What histopathological features are seen in Lymphomatoid Papulosis?

Answer 56

Atypical cells express one or more T-cell antigens and the lymphoid activation antigen CD30.

Question 57

What does a CD4-to-CD8 ratio of more than 10 indicate in Sézary Syndrome?

Answer 57

An expanded CD4+ T-cell population resulting in a CD4-to-CD8 ratio of more than 10 is a diagnostic criterion for Sézary Syndrome.

Question 58

What is the primary cause of mortality in Sézary Syndrome?

Answer 58

The primary cause of mortality in Sézary Syndrome is infectious complications due to very little normal immunity left.

Question 59

What is the diagnosis for a patient with diffuse erythroderma and circulating malignant T cells?

Answer 59

The diagnosis is Sézary Syndrome, with an unfavorable prognosis and a 5-year overall survival rate of 24% to 43%.

Question 60

What does loss of CD7 and CD26 expression indicate in Sézary Syndrome?

Answer 60

Loss of CD7 and CD26 expression is frequently observed in Sézary Syndrome and is useful in identifying Sézary cells.

Question 61

What is the prognosis for Folliculotropic Mycosis Fungoides?

Answer 61

Folliculotropic Mycosis Fungoides has a worse prognosis, with 5-year survival rates of approximately 41%.

Question 62

What distinguishes Pagetoid Reticulosis from classic Mycosis Fungoides?

Answer 62

Pagetoid Reticulosis is distinguished by its solitary lesion, more prominent epidermotropism, and lack of extracutaneous dissemination.

Question 63

What histological findings support a diagnosis of granulomatous slack skin?

Answer 63

Histology shows a dense granulomatous infiltrate in the dermis, macrophages, multinucleated giant cells, and loss of elastic fibers.

Question 64

What is the significance of aberrant expression of CD158k/KIR3DL2 in Sézary Syndrome?

Answer 64

Aberrant expression of CD158k/KIR3DL2 is a useful marker for identifying Sézary cells.

Question 65

What is the prognosis for primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma?

Answer 65

The prognosis is generally favorable with a 10-year survival rate of nearly 100%, but monitoring is required.

Question 66

What are the treatment options for solitary or localized skin lesions in Cutaneous Anaplastic Large-Cell Lymphoma?

Answer 66

The treatment of choice is excision or radiotherapy, with other options including PUVA in combination with interferon-α.

Question 67

What is the most common phenotype observed in Cutaneous Anaplastic Large-Cell Lymphoma?

Answer 67

The most common phenotype observed is CD4+ T-helper phenotype.

Question 68

What are the clinical findings associated with Subcutaneous Panniculitis-Like T-Cell Lymphoma?

Answer 68

Clinical findings include subcutaneous nodules and plaques, predominantly affecting the legs and trunk.

Question 69

What is the significance of TCR rearrangement in lymphomatoid papulosis?

Answer 69

Monoclonal TCR rearrangement may be prognostic for disease more likely to develop lymphomatoid papulosis-associated lymphomas.

Question 70

What is the long-term management strategy for lymphomatoid papulosis?

Answer 70

Long-term follow-up without active treatment is recommended for patients with few, nonscarring lesions.

Question 71

What is the treatment of choice for localized lesions in primary cutaneous anaplastic large-cell lymphoma?

Answer 71

Excision or radiotherapy is the treatment of choice for solitary or localized skin lesions.

Question 72

What chromosomal rearrangement is associated with lymphomatoid papulosis?

Answer 72

The IRF4/DUSP locus on chromosome 6p25 is associated with this variant of lymphomatoid papulosis.

Question 73

What does a tumor expressing CD30 but lacking ALK indicate?

Answer 73

This indicates that primary cutaneous anaplastic large-cell lymphomas are usually negative for ALK.

Question 74

What are the histopathological features of subcutaneous infiltrates in T-cell lymphoma?

Answer 74

Features include a mixture of neoplastic pleomorphic cells and rimming of individual fat cells by neoplastic T cells.

Question 75

What is the prognosis for α/β type of subcutaneous panniculitis-like T-cell lymphoma?

Answer 75

The α/β type responds well to systemic corticosteroids, leading to an excellent prognosis with a 5-year survival rate of 85%.

Question 76

What are the clinical findings associated with Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type?

Answer 76

Clinical findings include destruction of the nasal region and skin lesions such as subcutaneous tumors and ulcers.

Question 77

What are the histopathological characteristics of Primary Cutaneous Aggressive Epidermotropic CD8+ Cytotoxic T-Cell Lymphoma?

Answer 77

Characteristics include band-like infiltrates and high frequency of Ki67 antigen expression.

Question 78

What is the prognosis for Primary Cutaneous Aggressive Epidermotropic CD8+ Cytotoxic T-Cell Lymphoma?

Answer 78

Even with multiagent chemotherapy, the course is aggressive with a median survival of approximately 32 months.

Question 79

What defines Cutaneous γ/δ T-Cell Lymphoma?

Answer 79

It comprises peripheral T-cell lymphomas with a clonal proliferation of mature, activated γ/δ T cells.

Question 80

What is the initial treatment approach for subcutaneous panniculitis-like T-cell lymphoma?

Answer 80

Systemic corticosteroids are the initial treatment approach for the α/β type.

Question 81

What is the typical prognosis for extranodal NK/T-cell lymphoma, nasal type?

Answer 81

The prognosis is poor, as this aggressive disease is often lethal within months.

Question 82

What is the median survival for primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma?

Answer 82

The median survival for this aggressive lymphoma is 32 months.

Question 83

What does expression of βF1 indicate in subcutaneous panniculitis-like T-cell lymphoma?

Answer 83

Expression of βF1 indicates a TCR α/β phenotype.

Question 84

What does the presence of EBV in tumor cells indicate in extranodal NK/T-cell lymphoma?

Answer 84

It indicates a viral association characteristic of extranodal NK/T-cell lymphoma, nasal type.

Question 85

What is unusual about the metastasis pattern in primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma?

Answer 85

Metastatic spread to unusual sites like the CNS is common, but lymph node involvement is not typically observed.

Question 86

What are the three major patterns of involvement in histopathology for cutaneous lymphomas?

Answer 86

The three major patterns are epidermotropic, dermal, and subcutaneous.

Question 87

What is the prognosis for patients with Primary Cutaneous Acral CD8+ T-Cell Lymphoproliferation?

Answer 87

The prognosis is favorable.

Question 88

What are the clinical features of indolent cutaneous, CD8+ lymphoid proliferation?

Answer 88

Features include solitary skin lesions on the face or acral sites.

Question 89

What is the median survival for aggressive disease resistant to multiagent chemotherapy?

Answer 89

Median survival is 15 months.

Question 90

What is a new discriminative marker for indolent CD8+ lymphoid proliferation?

Answer 90

CD68 could be a new discriminative marker.

Question 91

What is the typical prognosis for cutaneous γ/δ T-cell lymphoma?

Answer 91

The prognosis is poor, with a median survival of 15 months.

Question 92

What is the prognosis for primary cutaneous acral CD8+ T-cell lymphoproliferation?

Answer 92

The prognosis is excellent, with complete remission lasting for years.

Question 93

What does strong positivity for TCR δ indicate in cutaneous γ/δ T-cell lymphoma?

Answer 93

It indicates a γ/δ origin of the lymphoma.

Question 94

What marker can help distinguish indolent CD8+ lymphoid proliferation from other CD8+ cutaneous lymphomas?

Answer 94

CD68- could be a discriminative marker.

Question 95

What are the key signaling pathways involved in cutaneous T-cell lymphoma?

Answer 95

Key pathways include JAK-STAT, NF-κB, TCR, Apoptosis, Cell Cycle, Genome Integrity, and Cytoskeletal Dynamics.

Question 96

What is the role of epigenetic regulators in cutaneous T-cell lymphoma?

Answer 96

Epigenetic regulators influence gene expression without altering the DNA sequence.

Question 97

What are the key regulators involved in apoptosis?

Answer 97

FAS and TNFRSF10A pathways trigger apoptotic signals. ## Footnote These pathways are crucial in cutaneous T-cell lymphoma.

Question 98

What role do epigenetic regulators play in cutaneous T-cell lymphoma?

Answer 98

Epigenetic regulators influence gene expression without altering the DNA sequence. ## Footnote Key regulators include ARID1A (chromatin remodeling), DNMT3A (DNA methylation), and KMT2C (histone modification).

Question 99

What is the function of ARID1A?

Answer 99

Chromatin remodeling. ## Footnote ARID1A is a key epigenetic regulator in cutaneous T-cell lymphoma.

Question 100

What is the function of DNMT3A?

Answer 100

DNA methylation. ## Footnote DNMT3A is a key epigenetic regulator in cutaneous T-cell lymphoma.

Question 101

What is the function of KMT2C?

Answer 101

Histone modification. ## Footnote KMT2C is a key epigenetic regulator in cutaneous T-cell lymphoma.

Question 102

How does the JAK-STAT pathway affect T-cells?

Answer 102

JAK-STAT pathway activation can lead to cell survival or apoptosis depending on the context. ## Footnote This pathway's role is crucial in the fate of T-cells in cutaneous T-cell lymphoma.

Question 103

What role does NF-κB signaling play in T-cell survival?

Answer 103

NF-κB signaling can promote cell survival, counteracting apoptotic signals. ## Footnote The balance between NF-κB and apoptotic signals determines T-cell fate in lymphoma.

Question 104

What is the significance of the balance between apoptotic and survival pathways?

Answer 104

The balance determines the fate of T-cells in the lymphoma context. ## Footnote This balance is crucial for understanding cutaneous T-cell lymphoma progression.

Question 105

What are the main components of the cell cycle regulation?

Answer 105

Key regulators include Rb, p16, and CDKN2A. ## Footnote These components are important in cell cycle control.

Question 106

What is the role of TP53 and ATM in genome integrity?

Answer 106

TP53 and ATM are critical for maintaining genome integrity. ## Footnote They help in DNA damage response and repair mechanisms.

Question 107

What are the key players in cytoskeletal dynamics?

Answer 107

Key players include RhoA, ERK, and AKT. ## Footnote These molecules are involved in regulating cytoskeletal structure and function.