Lymphoproliferative and myeloproliferative disorders Flashcards
1
Q
Jessner’s epidemiology
A
- middle aged adults
- no gender predilection
2
Q
Jessner’s pathogenesis
A
- Controversial entity: some believe it is a variant of lupus or PMLE, versus pseudolymphoma
- Co-occurrences with: lupus, PMLE, Lyme disease
- Rarely: drug induced: ACEI, glatiramer acetat
3
Q
Jessner’s Clinical
A
- Distribution: head, neck, upper back (think acne)
- Asymptomatic erythematous papules, plaques and nodules. Can have annular plaques with central clearing
- No epidermal change
- Last several weeks to months
- No systemic involvement
- Spontaneous resolution occurs, but can recur
4
Q
Jessner’s Histology
A
- Grenz zone
- No, or very sparse, interface dermatitis
- Superficial and deep peri-vascular lymphocytic infiltrate that may be peri-appendageal
- Mildly increased mucin
- Immunohistochemistry:
- Mixed T-cell infiltrate with a predominance of CD8 lymphocytes
- Mixed with CD123 plasmacytoid denritic cells
- Distribution of the dendritic cells is identical to what is seen in LE tumidus
5
Q
Jessner’s ddx
A
- Infectious: borderline lepromatous leprosy
- Immune: PMLE, lupus tumidus, granuloma faciale
- Infiltrates: pseudolymphoma, REM
- Neoplastic: cutaneous lymphoma
6
Q
Jessner’s treatment
A
- PAGED:
- education: can resolve spontaneously within months to years, without scarring
- TOPICAL
- Topical steroids and calcineurin inhibitors
- Oral systemic:
- 50% improvement with plaquenil
- 76% improvement with thalidomide compared to 16% placebo (crossover study)
- Procedural:
- excision
- resistant to radiation therapy,
- cases of PDL and chemo and PDT
- Caution light as ??lupus/PMLE ddx
- Intra-lesional steroids –> limited success
- Camouflage and cosmetic
7
Q
Pseudolymphoma epidemiology
A
Children and adults
8
Q
Pseudolymphoma pathogenesis
A
- Exaggerated local immunologic reaction to stimulus (often underrecognised)
- Hapten driven immunologic response –> cells damaged by toxic effect of stimuli
9
Q
Pseudolymphoma causative agents
A
- Anything that externally compromises the skin barrier
- Arthropod bites
- Tattoos
- Vaccinations
- Contact allergens
- Contact allergens
- Metal implants
- Infections
- Lyme disease
- Herpes Zoster
- Medications - has a crossover with DRESS drugs. You can have DRESS patients who have atypical lymphocytes in the blood and skin
- Anti-convulstants
- Anti-arrhythmics
- Antibiotics
- Antidepressants
- Anti-histamines
- Antihypertensives
- Anti-psychotics
- Chemotherapy
- Lipid lowering drugs
- NSAIDs
- Allopurinol, dapsone, etc
- Benzos
- Steroid hormones
- Can also be unknown!
10
Q
Pseudolymphoma clinical
A
- Single, firm 1-3 cm erythematous to violaceous plaque or nodule
- Head, neck or upper extremities
- Can be multiple, clustered papules
- Can be large panniculitis like nodules
- Lacks scale
11
Q
B cell Pseudolymphoma histology
A
- Superficial and deep nodular or diffuse infiltrate of lymphocytes
- Admixed histiocytes, and occasional plasma cells and eosinophils
- When florid: germinal centres with prominent tingible body macrophages
12
Q
T cell Pseudolymphoma histology
A
- CD4 T helper lymphocytes are commonly observed within the dermis, admixed with a minority of CD8 cytotoxic/suppressor T cells
- Drug induced - may have an MF-like pattern
- May see: epidermotropism, spongiosis, vacuolar degeneration, papillary dermal oedema, red cell extravasation
- There is no prominent papillary dermal fibrosis (which you see in MF), but T cell clonality may be present
13
Q
B cell Pseudolymphoma immunohistochemistry and clonality analysis
A
Immunohistochemistry
- Distinct B and T cell compartments
- CD35 or CD21 visualize networks of follicular dendritic cells within reactive germinal centres
- Germinal centre cells have a normal CD20, CD10, BCL6, BCL2
- High proliferative rate: MIB-1
Clonality analysis
- Clonality of IgH gene rearrangement or restricted kappa or delta expression is not seen in pseudolymphoma
- Detection of monoclonal expression of immunoglobulin light chains kappa or delta is a key diagnostic feature for primary cutaneous marginal zone B cell lymphoma. Monoclonaltiy is >10:1 ratio
14
Q
How is Pseudolymphoma different to follicle centre B cell lymphoma?
A
- It has a mixed cellular infiltrate such as eosinophils and plasma cells. B cell lymphoma is predominantly lymphocyte
- It has a reactive germinal centre with a mantle zone and tingible body macrophages present
- It has polarization of follicles with light and dark areas. B cell lymphoma has monomorphous appearance of follicles without polarization
- Immunophenotypically it has:
- T and B lymphocytes. B cell has CD20 B lymphocytes
- Bcl-6 cells are restricted to lymph follicles. in B cell lymphoma the Bcl-6 cells are outside of lymph follicles
- Bcl-2 are only on T lymphocytes.
- High proliferation of germinal centres
- Mixed kappa and delta expression (restricted in B cell lymphoma)
15
Q
CD30 Pseudolymphoma histology
A
- persistent arthropod bite reactions, drug reactions, atypical lymphoid infiltrates associated with cutaneous poxvirus infections.
- Has polyclonal arrangement of TCR
16
Q
Pseudolymphoma ddx
A
External: Trauma: arthropod bites, tattoo reaction Infective: Lyme disease, Syphilis Drug: eruptions Internal: Papulosquamous: lichen sclerosus, PLEVA, PPD, contact dermatitis Immune: lupus Infiltrates: pseulymphomatous folliculitis
- Neoplastic:
- Primary cutaneous marginal zone lymphoma
- some argue that these are on the same spectrum
- PCMZL has plasma cells at the periphery of lymphocyte infiltrate
- Demonstration of monotypic palsma cells with either kappa or lambda light chains distinguishes PCMZL
- Primary cutaneous follicle centre lymphoma
- Presence of eosinophils favours pseudolymphoma
- Secondary cutaneous follicular lymphoma
- Primary cutaneous marginal zone lymphoma
Rare: APACHE, IgG4, plasmacytosis, hydroa vaccinforme, Kikuchi Fujimoto
17
Q
What is a tingible body macrophage
A
- Type of macrophage in germinal centres that contains phagocytosed, apoptotic cells which are degrading
- Tingible means: staining
- May play a role in downregulating germinal centre reaction .–> released prostaglandins, and hence a reduced B-cell induction of IL-2
18
Q
APACHE
A
- Acral pseudolymphomatous angiokeratoma of children
- Favours the extremities of children between 2-16 years
- Unilateral grouping of small, red-violet angiomatous papules
- Histologically: dermal infiltrates of lymphocytes, histiocytes and plasma cells with prominently thickened capillaries
19
Q
Kikuchi-Fujimoto: histiocytic necroziting lymphadenitis
A
- Idiopathic systemic inflammatory disease
- Young adult women
- Associations: viral (EBV, CMV), bacterial and autoimmune
- Systemic: fevers, weight loss, GIT symptoms, cervical lymphadenopathy
- Cutaneous: 40% of patients –> acneiform eruptions, urticaria, ulcers, indurated erythematous plaques
- Histo:
- Of skin: dense superficial and deep perivascular lymphohistiocytic infiltrates with nuclear debris (without neutrophils) and interface change
- Histology of nodes: necrosis and histiocytic infiltration of the paracortical areas of involved lymph nodes (without identifiable pathogen)
20
Q
Pseudolymphomatous folliculitis
A
- Solitary facial nodule
- Peri-follicular and peri-adnexal dermal infiltrate
- Infiltrate is mixed, with T or B dominating. There may be cellular atypia and granulomas
- Irregular hyperplasia and distortion of the follicular epithelium
- Blurring of DEJ, CD1a/S100 mononuclear cells surround and infiltrate these distorted follicles
- Needs to be distinguished from CD4 T cell lymphoproliferative disorder (has more pleomorphism, and has PD1 expresion)
21
Q
Cutaneous and systemic plasmacytosis
A
- Benign condition
- Aetiology unknown - ?reactive dysfunction of plasma cells triggered by various stimuli
- Similar to Castlemans: elevated IL-6 in blood and tissue, but no HHV-8 infection
- Seen in Asians (particularly Japanese)
- Multiple reddish-brown, infiltrated maculopapules and plaues
- Distribution: commonly the trunk
- Systemic: lymphadenopathy, hepatosplenomegaly, interstitial penumonia, mesangial proliferative GN
- +/- anaemia, B symptoms, hypergammaglobulinaemia
- Histology: dense superficial and deep peri-vascualr infiltrates of mature polyclonal plasma cells
- To demonstrate polyclonality: kappa and lambda immunohistochemistry or FISH
22
Q
Pseudolymphoma treatment
A
- Benign –> treat conservatively
- May resolve without scarring
- Persistent lesions:
- Topical steroids
- Oral systemic: thalidomide for recalcitrant, or treat Lyme disease
- Procedural:
- simple excision
- cryosurgery
- laser ablation
- radiation therapy
- Biopsy –> can stimulate regression
- Intra-lesional steroids
- Camouflage
- Monitor
23
Q
Extramedullary Haematopoiesis epidemiology
A
- Neonates
- Can occur in adults with myelofibrosis and less often myelodysplasia or after a splenectomy
24
Q
Extramedullary Haematopoiesis pathogenesis
A
- Reflects bone marrow dysfunction
- Occurs during early embryogenesis and usually stops prior to birth
- After that, it can occur as a secondary phenomenon when the bone marrow function is altered
25
Q
Extramedullary Haematopoiesis clinical
A
- Erythematous to violaceous papules and nodules, that may ulcerate
- Blueberry muffin baby: widely disseminated. Can be seen in associated with congenital viral infections and prenatal anaemias
- Dermal haematopoiesis is most commonly seen with:
- Rubella
- CMV
- Associated cutaneous neoplasms: PPHIS
- Pilomatricoma
- Pyogenic granuloma
- Haemangioma
- Sebaceous naevus
26
Q
Blueberry muffin baby syndrome Ddx
A
- External
- Infections:
- Pre-natal
- TORCH
- Coxsackie
- Parvovirus
- Infections:
- Internal
- Neoplastic
- Myelodysplasias
- Congenital Leukaemia
- Congenital alveolar rhabdomyosarcoma
- Congenital LCH
- Neonatal neuroblastoma
- Congenital leukaemia cutis
- Vascular
- Haemangiomatosis
- Glomuvenous
- Multifocal lymphangioendothleiomatosis
- Disseminated extramedullary haematopoiesis
- Metabolic
- Anaemias: pre-natal, haemolytic, twin-twin transfusion
- Haemorrhage
- Neoplastic
27
Q
Extramedullary Haematopoiesis histology
A
- Dermal infiltrate of immature red and white blood cell precursors and megakaryocytes, centred around vessels of the superficial vascular plexus
- Can extend into the deeper reticular dermis and exhibit a diffuse pattern
- All three haematopoietiic cell lines are present in varying ratios: erythrocytes, leukocytes, megakaryocytes
28
Q
Extramedullary Haematopoiesis ddx
A
- limited histologically
- Distinguishing it from congenital leukaemia cutis and neonatal neuroblastoma is important –> leukaemia cutis has just leukocytes and not the others
- Patients with overwhelming marrow involvement from leukaemia may have both EMH and leukaemic involvement of the skin which may make things confusion
