Skin Cancer 3

Question 1

What are 75% of most cutaneous lymphomas?

Answer 1

T cell

Question 2

What are cutaneous T cell lymphoma?

Answer 2

1. Heterogenous group of neoplasms of skin-homing T-cells

2. show considerable variation in clinical presentation, histological appearance, immunophenotype and prognosis

Question 3

What are the most common subtypes of cutaneous T cell lymphoma?

Answer 3

• Sezary syndrome

- Mycosis fungoides

Question 4

What is the underlying molecular pathogenesis of CTCL?

Answer 4

• unknown

- inactivation of genes controlling cell cycle and apoptosis has been identified

Question 5

What is the epidemiology of T cell lymphoma?

Answer 5

• Mycosis fungoides 0.4/100,000
• Typically older adults (median age of diagnosis 55-60)
• Sézary syndrome is rare - <5% of all CTCL

Question 6

What is mycosis fungoides?

Answer 6

Common variant of primary CTCL and accounts for 50% of all primary cutaneous lymphoma

Question 7

What does diagnosis of cutaneous T cell lymphoma require?

Answer 7

• Indolent clinical course

* Diagnosis requires skin biopsy

Question 8

How long can diagnosis of mycosis fungiodes take?

Answer 8

• Diagnosis may take years as skin lesions may be present that are neither clinically nor histologically diagnostic for many years
• Atypical T-cell infiltrates may also be found in lymphomatoid drug eruptions
• Patches or plaques

Question 9

What is the progression of mycosis fungiodes?

Answer 9

patch stage → plaque stage → (finally) tumour stage disease

years to decades

Question 10

What is the duration of mycosis fungoides?

Answer 10

• Generally many years of nonspecific eczematous or psoriasiform skin lesions
• Median duration of onset of skin lesions to diagnosis of MF is 4-6 years, but may vary from several months to more than 5 decades

Question 11

How is the early patch stage of mycosis fungoides characterised?

Answer 11

variably sized erythematous, finely scaling lesions which may be mildly pruritic

Question 12

What is the pathogenesis of mycosis fungoides?

Answer 12

stepwise accumulation of genetic abnormalities → clonal proliferation → malignant transformation → progressive and widely disseminated disease

Question 13

What are the molecular events in mycosis fungoides?

Answer 13

unidentified

Question 14

What are the genetic abnormalities of Mycosis fungoides?

Answer 14

• P53, CDKN2A, PTEN, STAT3 identified in advanced MF, but not early
  e. g. likely secondary genetic events
• Persistent antigenic stimulation plays a crucial role in various lymphomas but no antigens known in MF

Question 15

What evaluation and investigation is needed in mycosis fungoides?

Answer 15

1. Type and extent of skin lesions
2. Presence of palpable lymph nodes
3. Skin biopsies
4. Complete blood counts and serum chemistries

Question 16

How do you treat the mycosis fungoides plaque/patch stage?

Answer 16

• topical corticosteroids
• phototherapy
• radiotherapy

Question 17

When do you give systemic chemotherapy in mycosis fungoides?

Answer 17

-advanced stage when there is nodal or visceral involvement or in patients with rapidly progressive tumours unresponsive to less aggressive therapies
•Brentuximab vedotin (anti-30)

Question 18

What are the 10 year survival rates in mycosis fungoides?

Answer 18

1. > 95% in limited patch / plaque disease
2. 85% in generalised patch / plaque disease
3. 42% in tumour stage disease
4. 20% in those with histological lymph node involvement

Question 19

What are the differential diagnosis for mycosis fungoides?

Answer 19

• psoriasis
• eczema (discoid)
• parapsoriasis

Question 20

What is the triad in sezary syndrome?

Answer 20

1. Erythroderma
2. Generalised lymphadenopathy
3. Presence of neoplastic T-cells (Sézary cells) in the skin, lymph nodes and peripheral blood

Question 21

What is sezary syndrome?

Answer 21

cutaneous T cell lymphoma

Question 22

What is the criteria for diangosis of sezary syndrome?

Answer 22

1. Demonstration of a T-cell clone in peripheral blood (eventhough skin) by molecular or cytogenetic methods
2. Demonstration of immunophenotypical abnormalities an expanded CD4+ T-cell population – resulting in a CD4/ CD8 ratio of greater than 10 and / or aberrant expression of pan-T-cell antigens)
3. An absolute Sézary cell count of at least 1000 cells per microlitre

Question 23

What is the treatment of sezary syndrome?

Answer 23

1. Systemic treatment is required
2. Extracorporeal photophoresis
3. Skin-directed therapies like PUVA or potent topical corticosteroids may be used as adjuvant therapy

Question 24

What is kaposi sarcoma?

Answer 24

• HHV8

* Multifocal systemic disease

Question 25

What can kaposi sarcoma look like?

Answer 25

• May be endemic or related to immunosuppression

* Cutaneous lesions can vary from pink patches to dark violet plaques, nodules or polyps

Question 26

What is the treatment of kaposi sarcoma?

Answer 26

1. chemotherapy (vincristine, doxorubicin, etoposide, bleomycin)
2. and / or radiation is favoured over surgery

Question 27

What is merkel cell carcinoma?

Answer 27

malignant proliferation of highly anaplastic cells which share structural and immunohistochemical features with various neuroectodermally derived cells, including Merkel cells

Question 28

What is merkel cell carcinoma associated with?

Answer 28

80% are associated with polyomavirus

Question 29

What is an aetiological factor for merkel cell carcinoma?

Answer 29

UV exposure

Question 30

Where is merkel cell carcinoma?

Answer 30

predilection for the head and neck region of older adults

Question 31

What does merkel cell carcinoma look like?

Answer 31

• solitary, rapidly growing nodule
• pink-red to violaceous, firm, dome shaped
• Ulceration can occur

Question 32

Is merkel cell carcinoma aggressive?

Answer 32

• Aggressive, malignant behaviour

* >40% develop advanced disease

Question 33

What is the treatment of merkel cell carcinoma?

Answer 33

1. Treated with surgery, radiation therapy
2. anti-PD1 (Pembrolizumab) / anti-PDL1 (Avelumab)
   - checkpoint inhibitors when metastasis present