View
223
Download
0
Category
Preview:
Citation preview
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 1/179
Clinicopathologic Conference
HMS Dermatopathology Course
October 20, 2006Vincent Liu, M.D.
Dermatology and DematopathologyUniversity of Iowa School of Medicine
Iowa City, IAAlison Z. Young, M.D., Ph.D.Dermatology
Virginia Mason Medical CenterSeattle, WA
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 2/179
HPI #1/11: Original Lesions,
2.3 years prior to admission• Erosions on scalpdeveloped soon after
beginning sumatriptin for headaches
• Subsequent diffuse scaly erythematouspapules and plaquesover the rest of the
body, resistant to topical steroid and
cephalexin
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 3/179
HPI #2/11: Outside
Dermatology Evaluation• Scarring alopeciaand multiple hyperkeratotic
erythematous plaqueson the trunk and arms
• Pathology of hyperkeratotic plaque: hypertrophic
lichenoid dermatitis with eosinophilia• Bloodwork: leukocytosis (13.6K) with negative ANA
• Topical and systemic corticosteroids andhydroxychloroquine-> some improvement
• Three months later, topical tacrolimusand cephalexin
course• Psoralen-UVA photochemotherapy
• 23 months prior to admission, erythematous lesionsaroseon face and left lower eyelid
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 4/179
HPI #3/11: Initial Presentation to
MGH Clinic (14 months PTA)• Tender 3-6 cm plaquesand nodulesover
face, trunk, and extremities, some eroded,
appearing lichenoid to hypertrophic toverrucous
• Bloodwork: rheumatologic serologiesnegative
• Treatment: topical tacrolimus andclobetasol cream
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 5/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 6/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 7/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 8/179
HPI #4/11: Squamous Cell
Carcinoma-like Lesions• Biopsy of verrucous lesion on right thigh: well-
differentiated invasive squamous cell carcinoma
• Left lower leg lesion removed by Mohs surgery
three weeks later, revealing well-differentiatedinvasive squamous cell carcinoma
• Treatment: isotretinoin (20 mg daily)
• On follow-up (10 months PTA) boggy,
erythematous, irregular thin plaquein the leftinframammary area and an oozing, crusted lesion over the left lateral deltoid seen, treated withtopical mupirocin
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 9/179
HPI #5/11: Hospital Admission #1
(8 months PTA)• Admitted through the ER for increased frequency of
palpitations and anxiety• CT scan: no PE or DVT, and bilateral axillary and
mediastinal lymph nodes at upper range of normal• Ophthalmology consult: left periorbital swelling anderythema, ectropion, lagophthalmos, and exposurekeratopathy, with positive Schirmer test bilaterally
• Rheumatology consult: no synovitis, myositis, or
acrosclerosis• Flow cytometry of peripheral blood: polyclonal B cells,normal T cells, normal CD4+:CD8+ ratio
• Isotretinoin increased to 40 mg daily
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 10/179
HPI #6/11: Evolution of Lesions
• New lesion on right lower abdomen: squamous cellcarcinoma
• New England Dermatological Society discussion: eruptive
keratoacanthomaversus squamous cell carcinomaversusverrucous carcinomaversus hypertrophic lichen planus versus lupus erythematosus
• Previous biopsy specimen testing: negativefor HPV
• Superinfection of lesions by Staphylococcus aureus,treated with cephalexin and tetracycline
• Mycophenolate mofetil begun (3 months PTA);isotretinoin discontinued
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 11/179
HPI #7/11: Hospitalization #2
(2-3 months PTA)• Some improvement noted two weeks after
mycophenolate begun, but then new
annular erythematous painful lesionswithnecrotic black central ulcerations developed
• Readmission to hospital
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 12/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 13/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 14/179
HPI #8/11: Evaluation on
Admission• Morphology: Painful erythematous targetand reniform
lesionswith central ulceration
• Distribution: chest, abdomen, back, bilateral arms, right
leg• Pleomorphism: varying stages of evolution – erythematous nodules
– lesions with central clearing – lesions with necrotic ulceration
• Distinction: from the original hyperkeratotic nodules onthe legs with minimal involvement of the scalp, palms, andsoles
• Associated finding: Left periorbital edema and erythema
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 15/179
HPI #9/11: Hospitalization #2
Work-up• CT scan chest/abdomen/pelvis: extensive bilateral axillary
and inguinal lymphadenopathy
• Skin biopsy, abdomen: acute spongiotic dermatitis with
numerous eosinophils, suggestive of a drug eruption • Cultures, skin: Staph aureus, Pseudomonas aeruginosa
• Treatment:
– Discontinuation of mycophenolate mofetil
– Levofloxacinbegun – Prednisonetaper
– Morphinepain control
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 16/179
HPI #10/11: Third rash
(1 month PTA)• Ten days later, new blanching erythematous
lesionsbetween target lesions on trunk andextremities: diagnosed as levofloxacin
hypersensitivity • Treatment: discontinued levofloxacin; started
topical mupirocin
• Response:
– Some of the ulcerated lesions flattened and crustedover, but most persisted
– Pain required narcotic analgesia
– Hair & nail testing negative for arsenic
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 17/179
HPI #11/11: Hospitalization #3
• Three weeks after discharge, fever (38
degrees F), purulent drainagefrom lesions
on the right foot and left axilla – Culture: S. aureus, P. aeruginosa
– Treatment: topical mupirocin
• Readmittedwith persistent fever
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 18/179
Past Medical History
• Eczemaat age 24, generalized but sparing
face, with winter exacerbation, treated with
topical steroids and tacrolimus• Migraineheadaches, treated with
sumatriptan
• History of one miscarriage
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 19/179
Social History
• Worked as secretary, currently on disability
• Married with children, lived with husband
• Smoked 1-1/2 packs daily; rare alcohol
• Traveled throughout Eastern U.S.
• Drank well water in childhood
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 20/179
Family History
• Mother died of lung cancer
• Father’s history unknown
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 21/179
Allergies and Medications
• Allergy to penicillin• Medications on Admission
– Prednisone
– Oxycodone – Morphine sulfate
– Lorazepam
– Zinc
– Citalopram
– Alendronate
– Gabapentin
– Erythromycin gel
– Mupirocin
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 22/179
Physical Examination
• General: awake, alert, tearful
• Vitals: febrile (T 38), tachycardic (105 bpm), bpWNL, resp WNL
• Skin:• Generalized, confluent annular ulcerated plaques, covering
>60-70% BSA
• Multiple 0.5-cm hyperkeratotic papules, predominantly onlegs
• Erosions and deep ulcerationson right neck, right breast, rightheel with green discharge
• Left periorbital swellingand erythema
• 2+ edemabilateral lower legs
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 23/179
Laboratory Tests
• CBC: anemia (Hct 31); leukocytosis (16.8) with left shift(93% neuts); thrombocytosis (733K)
• Chemistry panel: WNL
• LFTs: WNL
• ANA: positive at 14 months prior to admission (1:640speckled); positive anti-U1 sn-RNP
• T-cell subsets: normal CD4:CD8 ratio (4 mos PTA)
• SPEP: abnormal pattern- v. low conc’n bands in gammaregion, IgG kappa M components (4 mos PTA)
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 24/179
Clinical Summary
• 44 year old Caucasian woman – 2.3-year history of generalized hyperkeratotic verrucous
papulonodules – admitted for fever and purulent drainagefrom ulcerated annular
plaquesand tumorsfor the past 2 months – following an episode of presumed levofloxacin cutaneous
hypersensitivity – with work-up to date notable for skin pathology interpreted as
squamous cell carcinomaand laboratory tests showing a positiveANA, positive anti-U1 snRNP, anemia, leukocytosis with a left
shift, and thrombocytosis – and minimal improvement to treatment with topical and systemic
steroids, topical tacrolimus, systemic hydroxychloroquine, PUVA,oral antibiotics, isotretinoin, and mycophenolate
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 25/179
Questions: Challenge to
Differential Diagnosis• Do all the patient’s cutaneous manifestations reflect the
same process (Occam’s razor )?
• If there are multiple processes, is there causalityin the
association? (What is primary and what is secondary?)• What is the true nature of the biopsies interpreted as
squamous cell carcinoma? (Could there be an element of pseudoepitheliomatous hyperplasia?)
• What is the role of the patient’s history of “eczema”? • What is the role, if any, of medication-induced
immunosuppression in the pathogenesis?
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 26/179
Goals
• To review the remarkably varied clinical
differential diagnosisfor disseminated
ulcerated, verrucous, plaques• To use the clinical and reported pathologic
data to arrive at a most likely diagnosis
• To try to account for the apparentlyevolving morphologyof the lesions
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 27/179
Goals
• To review the remarkably varied clinical
differential diagnosisfor disseminated
ulcerated, verrucous, plaques• To use the clinical and reported pathologic
data to arrive at a most likely diagnosis
• To try to account for the apparentlyevolving morphologyof the lesions
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 28/179
Differential Diagnosis:
Disseminated verrucouspapulonodules
??????
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 29/179
Differential Diagnosis:
Disseminated verrucouspapulonodules
• Disseminated squamous cell carcinomas
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 30/179
Disseminated Squamous Cell
Carcinomas: Clinical Settings• Sun-exposed• Scars (Marjolin’s)
– Trauma
– Burns
– Frostbite – Vaccination scars
– Pyoderma gangrenosum
• Underlying conditions – Dystrophic epidermolysis bullosa
– Hailey-Hailey disease
– Porokeratosis
– Discoid lupus erythematosus
– Lichen planus
• Immunosuppression- organ transplant recipients
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 31/179
Squamous Cell Carcinomas:
Clinical
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 32/179
Squamous Cell Carcinomas:
Clinical
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 33/179
Disseminated Squamous Cell
Carcinomas: Pathology• Architecture:
– Nests of atypical squamous epithelium arising from the
epidermis and extending into the dermis
– Foci of keratinization
• Cytomorphology:
– Eosinophilic cytoplasm
– Nuclear pleomorphism and hyperchromasia
– Mitoses
– Dyskeratosis
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 34/179
Squamous Cell Carcinomas:
Pathology
Differential Diagnosis:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 35/179
Differential Diagnosis:
Disseminated verrucous
papulonodules• Disseminated squamous cell carcinomas – Multiple keratoacanthomas
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 36/179
Multiple Keratoacanthomas:
Clinical• Types
– Ferguson-Smith (hereditary, self-healing)
– Grzybowski (eruptive)
– Mixed (overlap features) – Localized (one side or area of body)
– Sites of trauma
– Sites of underlying dermatosis
– Muir-Torre syndrome• Associations – Visceral malignancy (GI tract) in Muir-Torre syndrome
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 37/179
Keratoacanthoma: Pathology
• Architecture:
– Crateriform, exoendophytic, keratinizing squamous
proliferation
– Central keratinous material
– Peripheral buttressing of edges
• Cytomorphology:
– Cellular enlargement
– Eosinophilic cytoplasm with “glassy” appearance
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 38/179
Keratoacanthoma: Clinical
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 39/179
Keratoacanthoma: Pathology
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 40/179
Multiple Keratoacanthomas as
Paraneoplastic Phenomenon?
Muir-Torre Syndrome• Familial cancer syndrome
• At least one sebaceous neoplasm – Adenoma
– Epithelioma
– Carcinoma
• At least one visceral malignancy – Gastrointestinal- hereditary nonpolyposis colorectal cancer syndrome
– Genitourinary tract tumors
– Breast carcinoma
– Lymphoma/leukemia• Other cutaneous neoplasms
– Keratoacanthomas – Squamous cell carcinomas – Multiple follicular cysts
• MSH2 gene mutation
Differential Diagnosis:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 41/179
Differential Diagnosis:
Disseminated verrucous
papulonodules• Disseminated squamous cell carcinomas – Multiple keratoacanthomas – Verrucous carcinomas
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 42/179
Verrucous Carcinomas: Clinical
• Location:
– Oral cavity
– Larynx – Esophagus
– Skin (plantar)
• Setting:
– Environmental carcinogen (tobacco, betel)
– HPV implicated (6, 11, 16, 18)
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 43/179
Verrucous Carcinoma: Clinical
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 44/179
Verrucous Carcinomas: Pathology
• Architecture:
– Exoendophytic papillomatous squamous proliferation
– Hyperparakeratosis
– Bulbous expansion of rete pegs (blunted, rather than jagged)
– Burrows and draining sinuses (epitheliomacuniculatum)
• Cytomorphology: – Well-differentiated squamous epithelial cells
– Low mitotic activity
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 45/179
Verrucous Carcinoma: Pathology
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 46/179
Pseudoepitheliomatous
Hyperplasia: Pathology
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 47/179
Pseudoepitheliomatous
Hyperplasia:
Pathologic Differential Diagnosis• Inflammatory
– Chronic irritation• Peristomal
• Trauma• Cryotherapy
• Chronic lymphedema
– Infections• Chromomycosis
• Sporotrichosis
• Aspergillosis
• Pyoderma
• Actinomycosis
• Chronic verrucous lesions inimmunocompromised patientswith HSV/VZV
– Dermal inflammatory processes• Halogenodermas
• Chondrodermatitis nodularishelicis
• Neoplastic – Spitz nevi
– Malignant melanoma
– Granular cell tumor – Cutaneous T-cell lymphoma
Differential Diagnosis:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 48/179
Differential Diagnosis:
Disseminated verrucous
papulonodules• Disseminated squamous cell carcinomas – Multiple keratoacanthomas – Verrucous carcinomas
• Variant of lupus erythematosus
– Hypertrophic variant – Lichen planus/lupus erythematosus overlap
• Disseminated infection – Mycoses
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 49/179
Mycoses: Clinical
• Systemic Mycoses – Coccidiodomycosis
– Blastomycosis
– Histoplasmosis – Cryptococcosis
– Paracoccidiodomycosis
• Dematiaceous Fungal Infections
– Chromomycosis – Phaeohyphomycosis
• Sporotrichosis
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 50/179
Systemic Mycoses:
Coccidiodomycosis• Clinical
– Acute self-limited pulmonary infection
– U.S. Southwest, Mexico, Central & South America
– Dissemination in immunocompromised – Verrucous plaques, subcutaneous abscesses, pustules, ulceration
– Erythema nodosum
• Pathological
– Pseudoepitheliomatous hyperplasia
– Non-caseating granulomas in the upper and mid dermis
– Thick-walled spherules (10-80 microns) within multinulceate giantcells
– Endospores within spherules (sporangia)
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 51/179
Systemic Mycoses: Blastomycosis
• Clinical – Three forms:
• Pulmonary
• Disseminated
• Primary cutaneous
– North America, Africa, India
– Crusted verrucous noduleor ulcerated plaque, widespread pustules, esp.face
• Pathological – Pseudoepitheliomatous hyperplasia
– Polymorphous dermal inflammatory infiltrate with giant cells
– Microabscesses
– Poorly formed granulomas
– Thick-walled yeasts (7-15 microns) with broad based budding within giantcells
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 52/179
Systemic Mycoses: Histoplasmosis
• Clinical – America, Africa, Asia
– Dimorphic soil fungus
– Lung is primary focus
– Immunosuppression predisposes to dissemination, with skin involved in5%
– Papules, ulcerated nodules, cellulitis-like areas, acneiform lesions, or erythroderma
– Erythema nodosum
• Pathological
– Pseudoepitheliomatous hyperplasia – Granulomatous inflammation of dermis into subcutis
– Parasitized macrophages
– Small ovoid yeast-like organisms (2-3 x 3-5 microns) with surroundingclear halo
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 53/179
Dematiaceous Mycoses:
Sporotrichosis• Clinical
– Inoculation into skin with trauma
– Ulcerative, verrucous, acneiform, erythematous lesions
• Pathological – Pseudoepitheliomatous hyperplasia
– Suppurative granulomas with concentric zones• Neutrophilic microabscess centrally
• Cuff of epithelioid and multinucleated histiocytes
• Outer cuff of lymphoplasmacytic infiltrate
– Round or oval (4-6 micron) organisms uncommon withasteroid bodies
Differential Diagnosis:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 54/179
Differential Diagnosis:
Disseminated verrucous
papulonodules• Disseminated squamous cell carcinomas – Multiple keratoacanthomas – Verrucous carcinomas
• Variant of lupus erythematosus
– Hypertrophic variant – Lichen planus/lupus erythematosus overlap
• Disseminated infection – Mycoses – Mycobacterial infection
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 55/179
Mycobacterial Infection: Clinical
Multiple Squamous Cell
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 56/179
p q
Carcinomas/Keratoacanthomas/
Verrucous Carcinomas: J udgment• Pros
– Pathology suggestive – Multiple lesions
documented
• Cons
– No clear underlyingassociation in this case
– No classic (GI/GU)malignancy
– No significant response
to systemic retinoids – Generalized
distribution
– Negative HPV testing
Differential Diagnosis:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 57/179
g
Disseminated verrucous
papulonodules• Disseminated squamous cell carcinomas – Multiple keratoacanthomas – Verrucous carcinomas
• Variant of lupus erythematosus
Differential Diagnosis:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 58/179
g
Disseminated verrucous
papulonodules• Disseminated squamous cell carcinomas – Multiple keratoacanthomas – Verrucous carcinomas
• Variant of lupus erythematosus
– Hypertrophic variant
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 59/179
Lupus Erythematosus,
Hypertrophic Variant: Pathology• Epidermis
– Hyperkeratosis
– Verruciform epidermal hyperplasia
– Follicular plugging
– Dermal-epidermal junction vacuolar interface dermatitis
– Thickened basement membrane zone
• Dermis:
– Superficial and deep perivascular and periadnexal lymphocyticinflammation
– Mucin deposition
– Transepidermal elimination of elastotic material
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 60/179
Lupus Erythematosus: Pathology
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 61/179
Lupus Erythematosus,
Hypertrophic Variant: Pathology
Differential Diagnosis:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 62/179
g
Disseminated verrucous
papulonodules• Disseminated squamous cell carcinomas – Multiple keratoacanthomas – Verrucous carcinomas
• Variant of lupus erythematosus
– Hypertrophic variant – Lichen planus/lupus erythematosus overlap
H pertrophic Lichen
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 63/179
Hypertrophic Lichen
Planus/Lupus Erythematosus
Overlap: Clinical• Generalized verrucous skin-colored to
erythematous plaques distributed in a
generalized fashion with photodistributed
predilection
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 64/179
Hypertrophic Lichen Planus:
Clinical
Hypertrophic Lichen
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 65/179
Hypertrophic Lichen
Planus/Lupus Erythematosus
Overlap: Pathology• Verruciform papillomatous hyperplasia with
brisk lichenoid lymphocytic inflammation
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 66/179
Lupus Erythematosus Variant:
J udgment• Pros
– Positive serologies
(ANA, anti-U1snRNP)
– Reports of squamous
cell carcinoma
development inhypertrophic lupus
erythematosus
• Cons
– Lacks other ARA
criteria for lupuserythematosus
– Generalized
distribution and density
of lesions unusual
Differential Diagnosis:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 67/179
g
Disseminated verrucous
papulonodules• Disseminated squamous cell carcinomas – Multiple keratoacanthomas – Verrucous carcinomas
• Variant of lupus erythematosus
– Hypertrophic variant – Lichen planus/lupus erythematosus overlap
• Disseminated infection
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 68/179
Infectious: Categories
• Mycoses – Systemic
• Coccidiodomycosis
• Blastomycosis
• Histoplasmosis
• Cryptococcosis
• Paracoccidiodomycosis (in AIDS)
– Dematiaceous• Chromomycosis
• Sporotrichosis
• Mycobacterial – Lepromatous leprosy
– Atypical mycobacterial• Treponemal
– Yaws
– Bejel
• Leishmanial
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 69/179
Lupus Erythematosus,
Hypertrophic Variant: Clinical• Discoid lupus erythematosus lesions with
verrucous, hypertrophicmorphology
• Disseminated lesions
– cutaneous LE
– systemic LE
• Photodistribution (face and arms)
• More recalcitrant to therapy
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 70/179
Lupus Erythematosus: Clinical
Differential Diagnosis:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 71/179
g
Disseminated verrucous
papulonodules• Disseminated squamous cell carcinomas – Multiple keratoacanthomas – Verrucous carcinomas
• Variant of lupus erythematosus
– Hypertrophic variant – Lichen planus/lupus erythematosus overlap
• Disseminated infection – Mycoses – Mycobacterial infection – Treponemal infection
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 72/179
Treponemal Infection, Yaws:
Clinical• Clinical – Primary: mother yaw enlarges, crusts, forms satellite pustules
– Secondary: systemic involvement of musculoskeletal and CNS withdaughter yaws and morbilliform eruption
– Tertiary: bone, joint, soft tissue deformity
• Pathological – Epidermis
• Acanthosis
• Papillomatosis
• Spongiosis
• Neutrophilic exocytosis – Dermis
• Diffuse infiltrate of plasma cells, lymphocytes, histiocytes, andgranulocytes
• No endothelial swelling
• Resemble condylomata lata
– Spirochetes between keratinocytes
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 73/179
Treponemal Infection, Yaws:
Pathology• Papillomatous epidermal hyperplasia,
spongiosis
• Intraepidermal microabscesses• Treponemes in epidermis
Differential Diagnosis:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 74/179
Disseminated verrucous
papulonodules• Disseminated squamous cell carcinomas – Multiple keratoacanthomas – Verrucous carcinomas
• Variant of lupus erythematosus
– Hypertrophic variant – Lichen planus/lupus erythematosus overlap
• Disseminated infection – Mycoses – Mycobacterial infection – Treponemal infection – Leishmanial infection
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 75/179
Leishmanial Infection: Clinical
• Protozoa transmitted by sandfly (“Baghdad boil”)
• Three types – Cutaneous
– Mucocutaneous
– Visceral (“kala azar”)
• Morphology: crusted, ulcerated papules;may have sporotrichoid spread
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 76/179
Leishmanial Infection: Pathology
• Irregular acanthosis
• Mixed infiltrate, vaguely granulomatous
• Intracellular organisms
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 77/179
Infectious:
J udgment• Pros
– Verrucous morphology
reflecting
pseudoepitheliomatous
hyperplasia
• Cons
– No clear exposure
– Chronic history
– No obvious underlying
immunosuppression
Differential Diagnosis:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 78/179
Disseminated verrucous
papulonodules• Disseminated squamous cell carcinomas – Multiple keratoacanthomas – Verrucous carcinomas
• Variant of lupus erythematosus
– Hypertrophic variant – Lichen planus/lupus erythematosus overlap
• Disseminated infection – Mycoses – Mycobacterial infection – Treponemal infection – Leishmanial infection
• Halogenoderma
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 79/179
Halogenoderma: Clinical
• Skin eruptions in response to exposure to
halides (bromide, iodide, fluoride)
• Acneiform papulonodular eruptions, pustular, vegetating plaques
• ?delayed hypersensitivity
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 80/179
Halogenoderma: Pathology
• Papillomatous epidermal hyperplasia
• Mixed inflammatory microabscesses with
ulceration
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 81/179
Halogenoderma:
J udgment
• Pros
– Morphology of
verrucous hyperplasia
could be consistent
• Cons
– No clear exposure
– Lacks acneiform or
pustular lesions
– Extensive distribution
of lesions atypical
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 82/179
Goals
• To review the remarkably varied clinical
differential diagnosisfor disseminated
ulcerated, verrucous, plaques• To use the clinical and reported pathologic
data to arrive at a most likely diagnosis
• To try to account for the apparentlyevolving morphologyof the lesions
Differential Diagnosis:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 83/179
Disseminated verrucous
papulonodules• Disseminated squamous cell carcinomas – Multiple keratoacanthomas – Verrucous carcinomas
• Variant of lupus erythematosus – Hypertrophic variant
– Lichen planus/lupus erythematosus overlap
• Disseminated infection – Mycoses – Mycobacterial infection – Treponemal infection – Leishmanial infection
• Halogenoderma• Cutaneous T-cell lymphoma
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 84/179
Cutaneous T-Cell Lymphomas:
WHO-EORTC Classification• Mycosis fungoides
• MF-variants – Pagetoid reticulosis
– Folliculotropic, syringotropic, granulomatous variants
• Subtype of MF – Granulomatous slack skin
• Sezary syndrome• CD30-positive lymphoproliferative disorders – Lymphomatoid papulosis
– Primary cutaneous anaplastic large cell lymphoma
• Subcutaneous panniculitis-like T-cell lymphoma
• Primary cutaneous peripheral T-cell lymphoma (PTL), unspecified
• Subtypes of PTL – Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma (provisional)
– Cutaneous gamma/delta-positive T-cell lymphoma (provisional)
– Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma (provisional)
• Adult T-cell lymphoma
• Angioimmunoblastic T-cell lymphoma
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 85/179
Cutaneous T-Cell Lymphomas:
WHO-EORTC Classification• Mycosis fungoides
• MF-variants – Pagetoid reticulosis
– Folliculotropic, syringotropic, granulomatous variants
• Subtype of MF – Granulomatous slack skin
• Sezary syndrome• CD30-positive lymphoproliferative disorders – Lymphomatoid papulosis
– Primary cutaneous anaplastic large cell lymphoma
• Subcutaneous panniculitis-like T-cell lymphoma
• Primary cutaneous peripheral T-cell lymphoma (PTL), unspecified
• Subtypes of PTL – Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma (provisional)
– Cutaneous gamma/delta-positive T-cell lymphoma (provisional)
– Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma (provisional)
• Adult T-cell lymphoma
• Angioimmunoblastic T-cell lymphoma
C
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 86/179
Cutaneous T-cell Lymphoma:
Clinical• Mycosis Fungoides
– Progression
• Patch
• Plaque• Tumor
• Erythroderma
– Sun-protected distribution
• CD30+ T-cell Lymphoproliferative Disorders – Lymphomatoid papulosis
– CD30+ anaplastic large cell lymphoma
M i F id
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 87/179
Mycosis Fungoides-
Background • History: Coined in 1806 by
Alibert for resemblance to
fungating tumors
• Epidemiology: Male:Female =2:1; Black > White; Median age
55 yo
• Incidence: 0.29/100,000/yr
• Etiology: ?HTLV-1; ?ionizingradiation; ?chronic antigen
stimulation (silicone breast
implants)
Cutaneous Lymphoma:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 88/179
Cutaneous Lymphoma:
Mycosis Fungoides, Patch Stage-
Clinical
Cutaneous Lymphoma:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 89/179
Cutaneous Lymphoma:
Mycosis Fungoides, Plaque Stage-
Clinical
Cutaneous Lymphoma:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 90/179
Cutaneous Lymphoma:
Mycosis Fungoides, Tumor Stage-
Clinical
C t L h M i
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 91/179
Cutaneous Lymphoma, Mycosis
Fungoides: Pathology
• Epidermis
– Epidermotropism of atypical lymphocytes
• Pautrier’s microabscesses
• Haloed lymphocytes along dermal-epidermal junction
– Relative paucity of spongiosis
• Dermis – Papillary dermal sclerosis
– Lymphocytic atypia
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 92/179
Mycosis Fungoides: Pathology
M i F id
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 93/179
Mycosis Fungoides:
Immunophenotype
• CD3 • CD20
M i F id
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 94/179
Mycosis Fungoides:
Immunophenotype
• CD4 • CD7
C t T C ll L h
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 95/179
Cutaneous T-Cell Lymphomas:
WHO-EORTC Classification• Mycosis fungoides
• MF-variants – Pagetoid reticulosis
– Folliculotropic, syringotropic, granulomatous variants
• Subtype of MF – Granulomatous slack skin
• Sezary syndrome
• CD30-positive lymphoproliferative disorders – Lymphomatoid papulosis
– Primary cutaneous anaplastic large cell lymphoma
• Subcutaneous panniculitis-like T-cell lymphoma
• Primary cutaneous peripheral T-cell lymphoma (PTL), unspecified
• Subtypes of PTL – Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma (provisional)
– Cutaneous gamma/delta-positive T-cell lymphoma (provisional)
– Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma (provisional)
• Adult T-cell lymphoma
• Angioimmunoblastic T-cell lymphoma
CD30+ P i C t
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 96/179
CD30+ Primary Cutaneous
Lymphoproliferative Disorders:
Clinical• Lymphomatoid papulosis
– Crops of red papulonodules, often localized – Remitting and recurring
• Primary cutaneous CD30+ T-cell
lymphoma – Larger, more persistent nodule
– Often ulcerated
CD30+ P i C t
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 97/179
CD30+ Primary Cutaneous
Lymphoproliferative Disorders:
Clinical
CD30+ Primar C taneo s
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 98/179
CD30+ Primary Cutaneous
Lymphoproliferative Disorders:
Clinical
CD30+ Primary Cutaneous
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 99/179
y
Lymphoproliferative Disorders:
Pathology• Epidermis
– Variable spongiosis, acanthosis
– Epidermotropism not characteristic
• Dermis
– Heavy mixed infiltrate of atypical lymphocytes
– Types
• A• B
• C
Differential Diagnosis:Disseminated verrucous
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 100/179
Disseminated verrucous
papulonodules• Disseminated squamous cell carcinomas
– Multiple keratoacanthomas – Verrucous carcinomas
• Variant of lupus erythematosus – Hypertrophic variant
– Lichen planus/lupus erythematosus overlap
• Disseminated infection – Mycoses – Mycobacterial infection – Treponemal infection – Leishmanial infection
• Halogenoderma• Cutaneous T-cell lymphoma
– Disseminated pagetoid reticulosis(Ketron-Goodman)
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 101/179
Pagetoid Reticulosis: Clinical
• History – Epidemiology
• Age: middle-aged to elderly
• Sex: M>F
– Course: acral hyperkeratotic plaques, slowly progressive
• Physical
– Morphology: verrucous, psoriasiform, hyperkeratotic patches, plaques, and nodules, usually on extremities
– Secondary Characteristics: hemorrhage and ulceration
– Distribution
• Localized: Woringer-Kolopp
• Disseminated: Ketron-Goodman
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 102/179
Pagetoid Reticulosis: Pathology
• Histology – Epidermal hyperplasia with hyperkeratosis
– Pattern• Lichenoid infiltrate
• Epidermotropism prominent, pagetoid and linear • Spongiosis variable
• Dyskeratosis variable
• Follicular, adnexal, and vascular involvement reported
– Cytomorphology• Medium/large pleomorphic T cells
• Hyperchromatic and cerebriform nuclei• Abundant vacuolated cytoplasm
• Dermal lymphocytic population normal
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 103/179
Pagetoid Reticulosis: Pathology
• Immunophenotype
– CD3+, CD4+, CD8- (majority)
– CD3+, CD4-, CD8+ (minority) – CD30+ (often)
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 104/179
Pagetoid Reticulosis: Pathology
Differential Diagnosis:Disseminated verrucous
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 105/179
Disseminated verrucous
papulonodules• Disseminated squamous cell carcinomas
– Multiple keratoacanthomas – Verrucous carcinomas
• Variant of lupus erythematosus – Hypertrophic variant
– Lichen planus/lupus erythematosus overlap
• Disseminated infection – Mycoses – Mycobacterial infection – Treponemal infection – Leishmanial infection
• Halogenoderma• Cutaneous T-cell lymphoma
– Disseminated pagetoid reticulosis(Ketron-Goodman)
– Aggressive epidermotropic cytotoxic CD8+ cutaneous lymphoma
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 106/179
Goals
• To review the remarkably varied clinicaldifferential diagnosis for disseminated ulcerated,verrucous, plaques
• To use the clinical and reported pathologic data toarrive at a most likely diagnosis• To review the entity of primary cutaneous
aggressive, epidermotropic, cytotoxic CD8-positive lymphoma
• To try to account for the apparently evolvingmorphologyof the lesions
Aggressive Epidermotropic CD8+
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 107/179
Aggressive Epidermotropic CD8+
CTCL: Evolution of Concept
Histologic Patterns
Immunophenotypic
Characterization
Clinical Observations
Cutaneous T-cell Lymphoma with
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 108/179
Suppressor/Cytotoxic (CD8)
Phenotype• Agnarsson BA et al. J AAD 1990;22:569-77.
Nine patients.
• CD8+ cutaneous T cell lymphoma can be rapidly progressive or chronic.
• Distinction cannot be made by histology alone.
• Rapid progression was associated with CD2-,
CD7+ phenotype.• Chronicity was associated with CD2+, CD7-
phenotype.
Clinical and Pathological
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 109/179
Spectrum of CD8-positive
Cutaneous T-cell Lymphomas• Lu E et al. J Cutan Pathol 2002;29:465-472.
• Four groups:
– Precedent history of rash progression similar to CD4+ MF (7)
– Long-standing localized plaques similar to PR (3)
– Erythroderma and peripheral blood involvement similar to SS (2)
– Cutaneous nodules (6)
• Histology: epidermotropism, prominent periadnexal
infiltration• Conclusion: Approximately half of CD8+ CTCL clinically
and histologically resemble CD4+ MF/SS
Primary Cutaneous Aggressive
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 110/179
Epidermotropic CD8+ Cytotoxic
T-cell Lymphoma: Clinical
• History
– Epidemiology
• Age: middle-aged to elderly
• Sex: M>F
– Symptoms: rapidly progressive ulcerated plaques
without antecedent patch-plaque evolution
– Associated Findings:
• Systemic involvement, including oral cavity, testis, lung, CNS,
soft tissues
• Lymph nodes spared
Primary Cutaneous Aggressive
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 111/179
Epidermotropic CD8+ Cytotoxic
T-cell Lymphoma: Clinical
• Physical
– Morphology: patches, plaques, and nodules – Secondary Characteristics: hemorrhage and
ulceration
– Distribution: generalized
– Other Findings: findings referable to systemic
involvement (oral cavity, lung, CNS, etc)
Primary Cutaneous Aggressive
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 112/179
Epidermotropic CD8+ Cytotoxic
T-cell Lymphoma: Pathology
• Histology
– Pattern
• Lichenoid infiltrate
• Epidermotropism prominent, pagetoid and linear
• Spongiosis variable
• Dyskeratosis variable
• Follicular, adnexal, and vascular involvement reported
– Cytomorphology
• Medium/large pleomorphic T cells
Primary Cutaneous Aggressive
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 113/179
Epidermotropic CD8+ Cytotoxic
T-cell Lymphoma: Pathology
• Immunohistochemistry
– CD3+, CD4-, CD8+, CD45RA+, CD45RO- – CD2-/+, CD5-/+, CD7+/-
– TIA-1+, bcl-2+, MIB-1+
– CD56+/- • Molecular Genetics
– TCR-gamma genes rearranged
Primary Cutaneous Aggressive
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 114/179
Epidermotropic CD8+ Cytotoxic
T-cell Lymphoma: Management
• Course
– Fatal outcome in most
– Mean survival 32 months
• Treatment
– Chemotherapy (purine analogs)
– Radiotherapy
– Allogeneic bone marrow transplant
– Avoid therapy (e.g. retinoids, IFN-alpha) thatenhances Th1-like cytokine profile
Cutaneous T-cell Lymphoma:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 115/179
Cutaneous T cell Lymphoma:
Specific Classification
• Pagetoid Reticulosis
– Hyperkeratotic, verrucous
plaques on hands and feet
– Woringer and Kolopp
(localized) vs. Ketron-
Goodman (disseminated)
– Prominent pagetoid spread
• Primary CutaneousAggressiveEpidermotropic CD8+ T-
cell Lymphoma – Eruptive papulonodules
with chronic patches and
psoriasiform plaques
– Papulonodules: prominent
acanthosis or even pseudoepitheliomatous
hyperplasia
Resolution: Disseminated PR versus
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 116/179
versus
Aggressive Epidermotropic CD8+CTCL
• “Generalized cases [of pagetoid reticulosis]
would currently likely be classified asaggressive epidermotropic CD8+ CTCL,
cutaneous gamma/delta-positive T-cell
lymphoma, or tumor-stage MF.” [WillemzeR, et al. Blood 2005;105:3768-3785.]
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 117/179
Perspective
Disseminated Hyperkeratotic Papulonodular Lesions
Primary Cutaneous Aggressive
Epidermotropic CD8+ CytotoxicT-cell Lymphoma
Disseminated Pagetoid Reticulosis
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 118/179
Goals
• To review the remarkably varied clinicaldifferential diagnosis for disseminated ulcerated,verrucous, plaques
• To use the clinical and reported pathologic data toarrive at a most likely diagnosis• To review the entity of primary cutaneous
aggressive, epidermotropic, cytotoxic CD8-positive lymphoma
• To try to account for the apparently evolvingmorphologyof the lesions
C i i S
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 119/179
Clinical Summary
• 44 year old Caucasian woman – 2.3-year history of generalized hyperkeratotic verrucous
papulonodules – admitted for fever and purulent drainagefrom ulcerated annular
plaquesand tumorsfor the past 2 months
– following an episode of presumed levofloxacin cutaneoushypersensitivity
– with work-up to date notable for skin pathology interpreted assquamous cell carcinomaand laboratory tests showing a positiveANA, positive anti-U1 snRNP, anemia, leukocytosis with a leftshift, and thrombocytosis
– and minimal improvement to treatment with topical and systemicsteroids, topical tacrolimus, systemic hydroxychloroquine, PUVA,oral antibiotics, isotretinoin, and mycophenolate
Synthesis:
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 120/179
Synthesis:
Two scenarios
• Separate processes
– Generalized keratoacanthomas/squamous cellcarcinomas as paraneoplastic phenomenon
– Drug rash
– Cutaneous T-cell lymphoma
• Unified process
– Possibly immunosuppression-associatedmanifestations of evolving lymphomatous
process
Scenario A
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 121/179
Exacerbation of
Primary Cutaneous Aggressive
Epidermotropic CD8+ Cytotoxic
T-cell Lymphoma
with Retinoid Use
Fully Evolved
Primary Cutaneous Aggressive
Epidermotropic CD8+ Cytotoxic
T-cell Lymphoma
Hyperkeratotic Papulonodules
As Early/SmolderingManifestation of Aggressive
Epidermotropic CD8+ Cytotoxic
T-cell Lymphoma
Scenario B
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 122/179
Exacerbation of
Primary Cutaneous Aggressive
Epidermotropic CD8+ Cytotoxic
T-cell Lymphoma
with Retinoid Use
Fully Evolved
Primary Cutaneous Aggressive
Epidermotropic CD8+ Cytotoxic
T-cell Lymphoma
Multiple
Keratoacanthomas
As
ParaneoplasticPhenomenon
Primary Cutaneous AggressiveEpidermotropic CD8+ T-cell
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 123/179
Epidermotropic CD8 T cell
Lymphoma:
J udgment• Pros
– Hyperkeratotic,
verrucous lesionscompatible with
reported morphology
– Ulcerated lesions
classic for morphology – Rapid downturn of
events compatible with
aggressive course
• Cons
– Somewhat uncertain
significance of evolving morphology
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 124/179
Diagnosis:Primary Cutaneous Aggressive
Epidermotropic CD8+ CytotoxicT-cell Lymphoma
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 125/179
Pathology
Alison Z. Young, M.D., Ph.D.
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 126/179
Skin Biopsy: Left elbow
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 127/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 128/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 129/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 130/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 131/179
CD3 CD20
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 132/179
CD4 CD8
Initial Diagnostic Consideration
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 133/179
Initial Diagnostic Consideration
• Mycosis Fungoides
• Note: The degree of atypia of the nuclei is
unusual.
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 134/179
Skin Biopsy: Right neck
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 135/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 136/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 137/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 138/179
Skin Biopsy: Right Abdomen
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 139/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 140/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 141/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 142/179
CD20 CD3
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 143/179
CD4
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 144/179
CD4
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 145/179
CD8
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 146/179
CD8
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 147/179
CD7
CD2
CD30CD25
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 148/179
Perforin
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 149/179
BF-1
Immunophenotype
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 150/179
Immunophenotype
• CD20-• CD3+
• CD8+
• CD4+ (scattered)
• CD7+
• CD2-
• CD30-
• CD25+
• Perforin+
• BF-1+
Molecular Diagnostics
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 151/179
Molecular Diagnostics
• Clonal rearrangement to V9 and V10 (TCR
gamma chain)
Final Pathologic Diagnosis
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 152/179
Final Pathologic Diagnosis
• Aggressive epidermotropic cytotoxic
CD8+ cutaneous T-cell lymphoma
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 153/179
Skin Biopsy: Right Thigh
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 154/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 155/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 156/179
Diagnosis
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 157/179
Diagnosis
• Atypical Squamous Proliferation suggestive
of Squamous Cell Carcinoma
• In retrospect: – No morphologic evidence of lymphoma
– No tissue available for immunophenotyping or
genetic studies
– Pseudoepitheliomatous hyperplasia as a
paraneoplastic phenomenon cannot be excluded
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 158/179
Skin Biopsy: Right Abdomen
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 159/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 160/179
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 161/179
Diagnosis
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 162/179
Diagnosis
• Acute Spongiotic Dermatitis with
Eosinophilia and Focal Interface Changes
• In retrospect – Atypical cells are present that likely represent
involvement by the patient’s lymphoma.
Epidermotropic CD8+ CTCL
• Aggressive clinical course (median survival 32
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 163/179
Aggressive clinical course (median survival 32months)
• Eruptive papules, plaques & tumors with centralulceration & necrosis
• Metastatic spread to spleen, lungs, liver, CNS, oralcavity & rarely to lymph nodes
• Band-like infiltrate of medium-sized pleomorphic Tcells with a CD3+, CD4-, CD8+ phenotype
• Prominent epidermotropism into an acanthoticepidermis with spongiosis and blistering in all stages
• Cases with fatal outcome are CD2- & CD7+• Rx: multi-agent chemotherapy, bone marrow
transplant
CD8+ CTCL vs Transformed MF
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 164/179
CD8+ CTCL vs PagetoidReticulosis
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 165/179
CD8+ CTCL vs CD30- CutaneousLarge T-cell Lymphoma
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 166/179
PEH in association with PrimaryCutaneous ALCL
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 167/179
AE1/AE3
CD30
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 168/179
Final Diagnosis
Aggressive CD8+ Epidermotropic
Cytotoxic CTCL with
Pseudoepitheliomatous Hyperplasia
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 169/179
Clinical Course
Corey Cutler, MD MPH FRCP(C)
Department of Hematologic Oncology andStem Cell Transplantation
Dana-Farber Cancer Institute
Clinical Course
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 170/179
• Received 8 courses of dose-intense
Cyclophosphamide, Adriamycin, Vincristine and
Prednisone (CHOP-14 x 8)
• Attains 1st Clinical Complete Remission
• Early Relapse – Responds to CHOP again
• Signs of early cutaneous recurrence within weeks
Clinical Course
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 171/179
• Undergoes Fully Ablative Allogeneic Stem
Cell Transplantation from a Matched,
Unrelated Donor
– Cyclophosphamide (1800 mg/m2 x 2)
– Total Body Irradiation (14 Gy in 7 fractions)
• Complete disappearance of all skin lesions
after near total desquamation
Clinical Course
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 172/179
• Day +24: New diffuse erythema – clinicallyand histologically consistent with acuteGraft-vs.-Host Disease (Stage 3 Skin,
Overall Grade IIC)• Responds to prednisone
• During prednisone taper (~day +150), new
plaque-like skin lesions noted over torso,limbs and scalp
Clinical Course
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 173/179
• Biopsy: Slight spongiosis with parakeratosis
and intracorneal pustules consistent with
early evolving psoriasis
• Responsive to topical high-potency
corticosteroid therapy
• Alive, with skin lesions of unknown
significance, day +165
Transplantation for CTCL
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 174/179
p
• Rarely performed;
• Heterogeneous literature – case reports,
case series(Molina et al , J Clin Onc 2005)
• Varying outcomes
• DFCI experience, n=3; All alive and
disease-free between 165-300 days; Allwith cutaneous GVHD
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 175/179
References: Disseminated Squamous
Cell Carcinomas
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 176/179
Cell Carcinomas
• Cruickshank AH, McConnell EM, Miller DG. Malignancy in scars,chronic ulcers, and sinuses. J Clin Pathol 1963;16:573-580.
• Lindelof B, Sigurgeirsson B, Gabel H, Stern RS. Incidence of skincancer in 5356 patients following organ transplantation. Br J Dermatol2000;143:513-519.
• Jayaraman M, Janaki VR, Yesudian P. Squamous cell carcinomaarising from hypertrophic lichen planus. Int J Dermatol 1995;34:70-71.
• Castano E, Lopez-Rios F, Alvare-Fernandez JG, et al. Verrucouscarcinoma in association with hypertrophic lichen planus. Clin Exp
Dermatol 1997;22P23-25.• Badell A, Marcoval J, Gallego I, et al. Keratoacanthoma arising in
hypertrophic lichen planus. Br J Dermatol 2000;142:380-382.
References: Lupus Erythematosus
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 177/179
• Santa Cruz DJ, Uitto J, Eisen AZ, Prioleau PG. Verrucous lupus erythematosus: Ultrastructuralstudies on a distinct variant of chronic discoid lupus erythematosus. J Am Acad Dermatol1983;9:82-90.
• Rubenstein DJ, Huntley AC. Keratotic lupus erythematosus: treatment with isotretinoin. J AmAcad Dermatol 1986;14:910-914.
• Van der Horst JC, Cirkel PKS, Nieboer C. Mixed lichen planus-lupus erythematosus disease: adistinct entity? Clinical, histopathological and immunopathological studies in six patients. Clin ExpDermatol 1983;8:631-640.
• Inaloz HS, Chowdhury MMU, Motley RJ. Lupus erythematosus/lichen planus overlap syndromewith scarring alopecia. J Eur Acad Dermatol Venereol 2001;15:171-174.
• Friss AB, Cohen PR, Bruce S, Duvic M. Chronic cutaneous lupus erythematosus mimickingmycosis fungoides. J Am Acad Dermatol 1995;33:891-895.
• Plotnick H, Burnham TK. Lichen planus and coexisting lupus erythematosus versus lichen planus-like lupus erythematosus. J Am Acad Dermatol 1986;14:931-938.
• Uitto J, Santa-Cruz DJ, Eisen AZ, Leone P. Verrucous lesions in patients with discoid lupus.Clinical, histopathological and immunofluorescence studies. Br J Dermatol 1978;98:507-520.
• Perniciaro C, Randle HW, Perry HO. Hypertrophic discoid lupus erythematosus resemblingsquamous cell carcinoma. Dermatol Surg 1995;21:255-257.
References: Infectious
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 178/179
• Quimby SR, Connolly SM, Winkelmann
RK, Smilack JD. Clinicopathologic
spectrum of specific cutaneous lesions of
disseminated coccidiodomycosis. J Am
Acad Dermatol 1992;26:79-82.
• Hobbs ER, Hempstead RW. Cutaneous
coccidiodomycosis simulating lepromatous
leprosy. Int J Dermatol 1984;23:334-336.
References: Cutaneous T-cell
Lymphoma
7/28/2019 Case 38, 2007-Gen Painful Ulcersted Lesions
http://slidepdf.com/reader/full/case-38-2007-gen-painful-ulcersted-lesions 179/179
Lymphoma• Burg G, Kempf W, Cozzio A, et al. WHO/EORTC classification of cutaneous lymphomas 2005:
histological and molecular aspects. J Cutan Pathol 2005;32:647-674.
• LeBoit PE. Variants of mycosis fungoides and related cutaneous T-cell lymphomas. Sem DiagPathol 1991;8:73-81.
• Agnarsson BA, Vonderheid EC, Kadin ME. Cutaneous T cell lymphoma with suppressor/cytotoxic(CD8) phenotypes: Identification of rapidly progressive and chronic subtypes. J Am Acad Dermatol1990;22:569-577.
• Price NM, Fuks ZY, Hoffman TE. Hyperkeratotic and verrucous features of mycosis fungoides.
Arch Dermatol 1977;113:57-60.• Tyring SK, Jones CS, Lee PC, et al. Development of verrucous plaques and gross hematuria in
advanced cutaneous T-cell lymphoma. Arch Dermatol 1988;124:655-656.
• Caputo R, Monti M, Berti E, et al. A verrucoid epidermotropic OKT8-positive lymphoma. Am JDermatopathol 1990;5:159-164.
• Courville P, Wechsler J, Thomine E, et al. Pseudoepitheliomatous hyperplasia in cutaneous T-celllymphoma. A clinical, histopathological and immunohistochemical study with particular interest inepithelial growth factor expression. Br J Dermatol 1999;140:421-426.
• Santucci M, Pimpinelli N, Massi D, et al. Cytotoxic/natural killer cell cutaneous lymphomas:Report of the EORTC cutaneous lymphoma task force workshop Cancer 2003;97:610 627
Recommended