CUTANEUS LYMPHOMA IN PATIENT WHO IS DIAGNOSED AS MORBUS

HANSEN AT BEGINNING

Hermawati AzikinA.Fachruddin Benyamin

Department of Internal MedicineMedical Faculty - Hasanuddin University

Case Report

BACKGROUND

Background

• Cutaneus lymphoma– Group of lymphoproliferative disorders: T & B

lymphocytes malignancy; part of extranodal NHL– In the US: CTCL incidence (1973-2002) 6.4/1

million people/yr– Adult & elderly people: average age 40-60 yr• Children & young people: sporadic case

– 80% manifested as CTCL

• Cutaneous T-cell lymphoma– In 1979, National Cancer Institute (NCI) introduced

CTCL: group of lymphoproliferative disorders characterized by the presence of neoplastic T cells in the skin

– Manifestations in the skin but in advanced stage can involved hematology, lymph nodes & visceral organs

– Etiology:• Unknown• Chromosome aberration, especially in advanced stage

CTCL

• WHO- EORTC classified CTCL into 2 subtypes : indolent & aggressive type

• Mycosis fungoides (MF)– Indolent subtype– The most common types of CTCL: 44%– Variant of MF (WHO/EORTC classification):• Sezary syndrome, folliculotropic MF, granulomatous

slack skin and pagetoid reticulosis (Woringer-Kolopp disease)

• The diagnosis of MF: history of the disease, clinical feature, histomorphologic & cytomorphologic feature, and cytogenetic examination

• Management of CTCL– Early stage: topical therapy w/wo interferon-α or

administration of oral agents– Advanced stage: chemotherapy

CASE REPORT

History Taking

• A male, 52 yo from Tual, admitted in Grestelina hospital with complaints patches on the skin all over the body

• First experienced 3 yrs ago, the patches & plaques raised on face, scalp, back, and chest initially, and then raised neck, body, and extremities

• In the course of illness:– fluid-filled lesions on the skin is reddish & fester– itchy patches & plaques especially when sweating– sometimes pain like puncture-pin

• Hair becomes brittle, pts had a hair loss and so did the eyebrows

• Subfebril fever during the disease but when admitted to Grestelina hospital no fever

• No cough, no history of contact with a cough person, no nausea, decreased of appetite, decreased of body weight. Defecation normal, micturation normal.

Previous Illness History

• 3 yrs ago: pts went to Dermatologist in Ambon & was diagnosed as Morbus Hansen wo any information about skin biopsy exam. He was given medication (drugs & topical) for 2 months

• History of contact with MH pts was denied, job was staff of PLN

• History drug user & free sex was denied. No DM, family history with the same disease was denied

• May 2013, the patient went to Ibnu Sina Dermatologist in Makassar– Skin biopsy results: skin malignancies– Therapy: methotrexate, oral and topical symptomatic therapy– Follow-up was carried out for 3 months with improved of

symptoms– No complete recovery, residence, & constraints to find time

for control discontinued methotrexate• Patches was recurred in all parts of the body especially

in chest, back & body fold• October 2013: pts was hospitalized in Grestelina with a

diagnosis of Cutaneous T-cell lymphoma/MF

Physical Exam

• Conscious/Adequate nutrition • Normal vital signs• Head– alopecia, red & black patches

on the scalp and face, side of the head look uneven shape, madarosis

• Neck : JVP R-2 cmH2O, no enlargement of lymph node, no tumor mass

• Thorax / Heart / Abdomen: Normal

• On the surface of the skin of all body & extremities: patches with hyperkeratosis plaque, excoriation & hypersquamation

• Fingernails especially the base of the finger was damaged & dull

Laboratory Exam

Oktober, 22nd 2013• WBC : 13.840 /µl• Hb : 11,1 gr/dl • PLT : 359.000 /µl• AST/ALT : 20/23 U/L• Ur/Cr : 5/0,60 mg/dl• ESR : 70 mm

Oktober, 31st 2013• WBC : 8.610 /µl• Hb : 11,4 g/dl• PLT : 207.000 /µl• Ur/Cr : 19,0/0,7 mg/dl• ESR : 40+/75+ mm

Abdominal US

Mei, 31st 2013 • Liver : enlarge with flat

surface, homogen echoparenchyme, no nodular lesion

• Impression : hepatomegaly

Histopathology

• Skin biopsy (July, 5th 2013)• Impression : cutaneus lymphoma (T-cell

lymphoma/mycosis fungoides)

• According to history taking, PE, & supporting exam, this pts was diagnosed as cutaneus T-cell lymphoma with mycosis fungoides type

DISCUSSION

DISCUSSION

• The pts was initially diagnosed as Morbus Hansen– skin lesion: patches & thickening of the skin as a plaques– damaged of hair follicles: alopecia– pain like punctured-pin: neuropathy– WITHOUT skin exam/biopsy

• In MH, skin manifestations: – diffuse erythema & thickening of the skin with infiltrates were

mainly found on the ears– face looks shiny & eyebrow usually be lost– hypopigmentation patches

• Granulomatous MF is a rare type of CTCL with a clinical picture that resembles lepromatous leprosy of MH

• Skin manifestations in early stage of MF– patchy hypopigmentation wo symptoms & lasts for several

years– no sensory defisit– skin lesions appear dry & dispigmentation multiple

ulcerated nodules– with anti-tuberculosis th/ in this pts no improvement,

which encourages further exam• After skin biopsy: CTCL• In the smear exam: no microorganisms• Histopathological exam: infiltrate of lymphocytes in

the dermis extending into the submucosa

WHO-EORTC Classification of Cutaneous Lymphoma

• CTCL:– Slow-growing cutaneus lymphoma– Psoriasiform or diffuse erythroderma lesions– Atypical lymphocytes in the circulation– Early stage: resemble other skin diseases so

difficult to enforce• There are 2 types: MF & Sezary syndrome• MF is the most common type of CTCL: 44%

Mycosis fungoides

• Malignant lymphoma characterized by the expansion of clon CD4 lymphocytes or T helper/T memory (CD45 + RO) which are normally present on the skin

• 1st introduced in 1806 by Alibert-Bazin, Dermatologist: severe disorder in the form of large tumors that undergo necrotic which resemble mushrooms

• The most common of CTCL (44%)– indolent type– 3 stages: patches (atrophic or non-atrophic), plaques sometimes

accompanied by lymphadenopathy, tumor that is susceptible to ulceration

– Lesion distribution: asymmetric & most often on the back, lower legs, groin, axilla & breast

Sezary syndrome

• Clinical symptoms & signs: skin edema, lymphadenopathy, hand & foot hyperkeratosis, alopecia, nail dystrophy, ectropion & organomegaly

• Skin lesions: hypopigmentation patch, erythematous with thickening of patches

• Aggressive type• 5% of all cases of MF

• In this pts also presented alopecia• Alopecia was experienced before pts got the

treatment– Alopecia was found in 2.5% of pts with CTCL– Folliculotropic MF– Infiltration of atypical lymphocytes in the epithelium

of hair that inhibits hair growth– May reversible or persistant: topical steroids and

interferon• Alopecia can also occur secondary to treatment

• Overall primary cutaneous lymphoma, 65% are T-cell type, the most common is positive of CD4 immunotype

• CTCL diagnosis is based on clinical symptoms and course of the disease based on cyto & histomorphologic feature– Blood tests (CBC) & blood smear– Liver function, uric acid & LDH– Flowcytometri– HIV & HTLV-1– Skin biopsy: atypical lymphocytes with lymph node biopsy

especially in pts with lymphadenopathy• Histopathological exam of MF pts seen a superficial bandlike

or lichenoid infiltrates, which is dominated by lymphocytes & histiocytes.

Sezary syndrome diagnosis: > 1 of the following criteria– Sezary cell count ≥ 1000 cells/uL– Abnormalities of the immune phenotype– T-cell clones in peripheral blood, as indicated by

molecular and cytogenetic methods• Flowcytometri also used to determine the differential

diagnosis of precursor T-cell & peripheral T-cell & NK-cell lymphoma

– Examination of the skin biopsy

Staging is based on skin manifestations & extra cutaneous manifestations:Stage IA: patches / plaques <10% of skin surface area (T1)Stage IB: patches / plaques> 10% of skin surface area (T2)Stage II B: visible tumor (T3)Stage III: thorough erythrodermaStage IVA A1: erythroderma and significant blood disorders A2: lymph node biopsy showing atypical cellsStage IVB: involvement of organs (liver, lung & bone marrow)

In this pts also conducted abdominal US hepatomegaly although in examination no organomegaly was foundPlan for further exam to ensure the staging of diseaseBased on physical examination & investigation in this pts, the patient is diagnosed as cutaneous T-cell lymphoma, mycosis fungoides staging IVB

• Management– Early stage: topical therapy w/wo interferon-α or other

oral medications– Advanced stage: chemotherapy & current therapy

• Some cytotoxic regimen had palliative function but survival benefit is still questionable

• In pts with advanced lesions, the choice of therapy is systemic therapy– 2nd line therapy for pts with skin lesions– Retinoids (bexarotene), IFN-α, low-dose MTX, histone

deacetylase inhibitors (HDACi), or denileukin diftiox– Effective in refractory disease

• Low-dose MTX– oral every week, initial dose 20-30 mg/wks 60-70 mg/wks

• HDACi: vorinostat– Can be well tolerated by the oral administration– Side effects: fatigue, light-moderate thrombocytopenia, elevated creatinine,

can be given together with PUVA, IFN-α, MTX or in combination with chemotherapy

• Monoclonal antibodies: alemtuzumab– Targeting therapy against lymphocyte Ag– Systemic therapy for the provision of etoposide, vincristine, SF & prednisone

oral reported to respond to 80% at the advanced stage CTCL or refractory MF• Transplantation is recommended for refractory younger pts or

advanced stage with the unresponsive to IFN-α, bexarotene, HDACi or denileukin diftitox

• In this pts is planned to administrate chemotherapy, but the patient is not willing to get this treatment– Pts received MTX with symptomatic th/ of oral & topical treatment

• In the early stages of MF lymphoma cells is largely limited to the skin and has a good response with only topical therapy

• In pts who only had partially respond especially at an advanced stage, it takes a systemic therapy

• Sandwich effect:– Rationalization of combination skin & systemic th/

even in pts with limited skin abnormality– Skin therapy works from the outside & systemic

therapy works from the inside– Mutually reinforce one another effect

• MF is a condition that can’t be cured in most pts except stage IA

• Mortality & prognosis according to the stage of disease at the time of first diagnosis

• The involvement of lymph nodes, organs & transformation to large T-cell lymphoma have an aggressive clinical forms & usually die

• Condition of this pts isn’t experienced significant improvement– Pts didn’t get optimal th/ like systemic chemotherapy

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