Mycosis Fungoides and Sezary Syndrome

Slide 1 · Mycosis Fungoidesand Sézary Syndrome

Clinical evolution · skin pathology · extracutaneous disease

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Define the two cutaneous mature T-cell neoplasms and their skin-homing biology.

Relate clinical phases of mycosis fungoides to histologic architecture.

Recognize the characteristic skin–blood–node presentation of Sézary syndrome.

Explain the principal course, prognostic and therapy distinctions.

Slide 3 · Two related neoplasms, two clinical patterns

Mycosis fungoides

Typically evolves from patches to plaques and tumors

May remain skin-localized for years

Blood circulation may be molecularly detectable without overt dissemination

Sézary syndrome

Generalized exfoliative erythroderma

Leukemia of atypical cerebriform T cells

Generalized lymphadenopathy

Slide 4 · Position within lymphoid neoplasia

Both are neoplasms of mature helper T lymphocytes.

Their shared biology is cutaneous tropism rather than a common clinical presentation.

They belong to the peripheral T-cell neoplasm discussion.

MF is also covered as a cutaneous T-cell lymphoma in the skin chapter.

Slide 5 · The neoplastic cell: A skin-homing CD4+ T cell

Clonal CD4+ T cell

CLA / CCR4 phenotype

Skin localization

The lymphoid lineage is helper T cell (CD4+).

The cells express molecules associated with cutaneous trafficking.

Clonal expansion produces the malignant infiltrate, not merely a reactive T-cell influx.

Slide 6 · Skin-homing biology explains cutaneous presentation

CLA + CCR4

Skin homing

Cutaneous infiltrate

Skin-directed trafficking is an integral property of these malignant T cells.

Cutaneous lymphocyte antigen (CLA) and CCR4.

The same kinds of homing molecules also operate in normal CD4+ T cells.

Slide 7 · Cutaneous lymphocyte antigen (CLA)

CLA is an adhesion-related surface determinant associated with skin homing.

Expression provides a biologic explanation for preferential cutaneous involvement.

CLA expression alone does not establish a malignant process.

Teaching distinction

Skin tropism is a biological property.

Malignancy requires additional morphologic and clonal evidence.

Slide 8 · CCR4 and the skin-tropic phenotype

CCR4 expression

Skin-directed trafficking

T-cell accumulation

CCR4 is a chemokine receptor identified by Robbins in these neoplasms.

Its presence accompanies other molecules that contribute to cutaneous localization.

The excerpt does not define a unique oncogenic CCR4 mutation or a specific ligand pathway.

Slide 9 · Homing is not equivalent to confinement

Cutaneous disease

Occult circulation

Possible late overt spread

A tumor can preferentially involve skin while its cells circulate through other compartments.

MF may show circulating cells by sensitive molecular methods early in its course.

Clinically evident extracutaneous disease in MF generally emerges late.

Slide 10 · A compartment-based framework

Skin-dominant phenotype

Patches, plaques, and cutaneous nodules

Superficial or deep dermal infiltration

MF often has an extended cutaneous phase

Multicompartment phenotype

Diffuse erythroderma

Peripheral blood leukemia

Generalized lymphadenopathy: Typical of Sézary syndrome

Slide 11 · Clonal T-cell receptor rearrangement

Atypical T cells

TCR gene analysis

Evidence of clonality

The neoplastic lymphocytes in MF harbor clonal T-cell receptor gene rearrangements.

T-cell receptor clonality provides molecular support for a T-cell clone.

Integrate a molecular result with lesion morphology and clinical context.

Slide 12 · No single specific driver mutation defines CTCL

A wide variety of altered oncogenes and tumor-suppressor genes.

None of these reported driver alterations is described as specific for CTCL.

The source therefore does not justify a single-mutation diagnostic algorithm.

Interpretive implication

Molecular heterogeneity ≠ a pathognomonic gene.

Preserve separation between clonality and a specific driver mutation.

Slide 13 · Phenotypic aberrancy can provide supportive evidence

Supported by Robbins

CD4+ helper T lineage

Possible aberrant T-cell antigen patterns

Clonal TCR rearrangements

Not established in this extract

A unique obligatory phenotype

A numerical immunophenotypic threshold

A pathognomonic mutation

Slide 14 · Integrated biological model of MF and Sézary syndrome

Clonal CD4+ T cells

CLA / CCR4 skin homing

Cutaneous disease ± extracutaneous involvement

Slide 15 · Mycosis fungoides: Essential definition

A cutaneous T-cell lymphoma of skin-homing helper T lymphocytes.

Typically presents with chronic evolving skin lesions.

In many patients it remains confined to skin clinically for years.

Central pathology concept

Atypical lymphocytes in superficial dermis + epidermis.

Clinical evolution and lesion architecture are connected.

Slide 16 · Clinical setting of mycosis fungoides

MF can develop at any age.

It most often affects adults older than 40 years.

Age is contextual—not a defining diagnostic requirement.

Slide 17 · Preferred distribution of skin lesions

Frequent: Trunk

Expanding skin involvement

Multiple body surfaces

Truncal skin is a usual location of early lesions.

Disease may eventually involve extremities, face and scalp.

The geographic distribution can broaden as cutaneous disease evolves.

Slide 18 · Three partially overlapping phases

Inflammatory / premycotic

Early patch-like eruption

Plaque

Indurated raised lesions

Tumor

Cutaneous nodules

Slide 19 · The premycotic phase resembles dermatitis

Observed appearance

Eczema-like lesions

Scaly, erythematous patches

Subtle or variable extent

Underlying process

Skin-homing neoplastic T-cell infiltrate

Potential epidermal invasion

Disease remains cutaneous clinically in many patients

Slide 20 · Patch lesions: Clinical morphology

Scaly red-brown patches are a typical form of MF.

Patches can resemble common inflammatory dermatoses.

Their appearance must be interpreted alongside clinical evolution and pathology.

Flat, red-brown scaly patch

Schematic illustration — not a clinical or histologic specimen

Slide 21 · Why patch disease is easily confused with eczema

The early cutaneous phenotype is as eczema-like.

Inflammatory clinical morphology can coexist with a clonal neoplastic infiltrate.

Clinical appearance and histology address different aspects of the same lesion.

Practical reasoning

Inflammatory appearance does not exclude lymphoma.

Anatomic infiltrate pattern helps explain the suspicion.

Slide 22 · Plaque lesions: The second recognizable pattern

Raised, indurated erythematous plaques may follow patches.

Plaques may have irregular outlines and scaling.

They indicate a more conspicuous cutaneous tumor burden.

Raised, indurated scaling plaque

Schematic illustration — not a clinical or histologic specimen

Slide 23 · A psoriasis-like appearance can mislead

Scaling plaques of MF can resemble psoriasis.

The clinical overlap does not mean their underlying mechanisms are the same.

Epidermal and superficial dermal lymphoid architecture becomes informative.

Compare the descriptions

Psoriasis-like: Raised, scaling plaque.

MF histology: Atypical T cells with epidermotropism.

Slide 24 · Tumor phase: Nodules become prominent

MF may develop multiple nodules or fungating tumors.

Nodules represent a change in the depth and distribution of tumor growth.

Progression to this phase correlates with greater systemic risk.

Protruding nodule / tumor

Schematic illustration — not a clinical or histologic specimen

Slide 25 · Ulceration and advanced cutaneous lesions

Plaques and tumor nodules can ulcerate.

An ulcerated lesion is a clinically important destructive cutaneous manifestation.

The presence of nodules or systemic spread is prognostically unfavorable.

Course relationship

Plaque or nodule → possible ulceration.

Tumor nodules → association with extracutaneous spread.

Slide 26 · Morphologic progression: External appearance

Patch

Flat and scaly

Plaque

Raised, indurated

Nodule / tumor

Expansile dermal lesion

Slide 27 · Histologic orientation: Epidermis and dermis

The epidermis is the superficial epithelial compartment.

The upper dermis lies immediately beneath it.

MF may involve both compartments, producing epidermotropism and a dermal infiltrate.

Layer-oriented schematic

Epidermis

Superficial dermis

Schematic illustration — not a clinical or histologic specimen

Slide 28 · Superficial dermal band-like aggregates

Atypical lymphocytes characteristically accumulate in the superficial dermis.

The infiltrate often forms a band-like distribution below the epidermis.

This arrangement must be considered alongside epidermal invasion.

Epidermis

Superficial dermis

Schematic illustration — not a clinical or histologic specimen

Slide 29 · Epidermotropism: Atypical lymphocytes in epidermis

Neoplastic lymphocytes move from their dermal distribution into epidermis.

Epidermal cells may be present singly or in small groups.

This epidermal invasion as a hallmark of patch/plaque MF.

Epidermis

Superficial dermis

Schematic illustration — not a clinical or histologic specimen

Slide 30 · Pautrier microabscesses are intraepidermal clusters

Groups of atypical T lymphocytes can form small epidermal collections.

These collections are termed Pautrier microabscesses.

Despite the name, they are clusters of lymphocytes—not ordinary neutrophilic abscesses.

Intraepidermal cluster

Epidermis

Superficial dermis

Schematic illustration — not a clinical or histologic specimen

Slide 31 · Cerebriform nuclear contours

Tumor T cells frequently possess markedly irregular nuclear membranes.

The nuclear membrane folds give a convoluted, cerebriform appearance.

This nuclear feature occurs in both cutaneous MF cells and Sézary blood cells.

Marked nuclear membrane infolding

Schematic illustration — not a clinical or histologic specimen

Slide 32 · Patch and plaque histology: A compartment pattern

Epidermotropism: Single atypical T cells within the epidermis.

Band-like infiltration beneath the epidermis.

Together, these encode the patch/plaque lesion pattern.

Epidermis

Superficial dermis

Schematic illustration — not a clinical or histologic specimen

Slide 33 · The tumor phase changes the architectural pattern

Advanced cutaneous nodules often show less conspicuous epidermotropism.

Malignant lymphocytes extend deeper into the dermis.

A nodular dermal growth pattern becomes clinically visible.

Deep dermal tumor mass

Epidermis

Superficial dermis

Schematic illustration — not a clinical or histologic specimen

Slide 34 · Loss of epidermotropism does not exclude advanced MF

Patch / plaque

Epidermal entry conspicuous

Upper dermal infiltrate

Small epidermal clusters may occur

Advanced tumor nodule

Epidermotropism may diminish

Deeper dermal growth prominent

Expansile nodular disease

Slide 35 · Why cutaneous nodules matter prognostically

Cutaneous tumor nodules

Higher-risk disease

Possible systemic spread

The presence of tumor nodules is associated with a worse course.

Tumor nodules correlate with the risk of systemic dissemination.

Surface area and extracutaneous involvement provide additional prognostic context.

Slide 36 · Subclinical blood and tissue circulation in MF

Molecularly detectable

Low-level tumor-cell circulation

May occur in apparently skin-limited disease

Requires interpretation of test sensitivity

Clinically overt

Nodal or visceral involvement becomes manifest

Typically later in MF course

Carries adverse clinical significance

Slide 37 · Histology and the clinical phase should agree logically

Clinical phase

Cutaneous finding

Pathologic pattern

Patch

Scaly erythematous patch

Epidermotropism + superficial infiltration

Plaque

Raised, indurated lesion

Epidermotropic atypical cells in skin

Tumor

Nodular or fungating mass

Deeper dermal tumor; epidermotropism may fade

Slide 38 · MF is not synonymous with every cutaneous T-cell lymphoma

CTCL includes several lymphoproliferative disorders affecting skin.

Robbins focuses here on MF as a distinctive skin-homing CD4+ neoplasm.

The clinicopathologic description should not be transferred to all CTCL entities.

Classification principle

Category: Cutaneous T-cell lymphomas.

Entity: Mycosis fungoides.

Slide 39 · A source-grounded evaluation sequence

Evolving skin morphology

Epidermal / dermal atypical T cells

Phenotype + TCR clonality

Slide 40 · What molecular testing contributes—and does not

Useful molecular evidence

Clonal TCR rearrangement

Possible aberrant antigen expression

Clonal nature of cutaneous infiltrate

Must also assess

Clinical presentation and evolution

Atypical cytomorphology

Epidermal versus dermal location

Slide 41 · Sézary syndrome: A distinct presentation

Erythroderma

Sézary-cell leukemia

Generalized nodes

Sézary syndrome is another tumor of skin-homing CD4+ T cells.

Its presentation combines generalized cutaneous and extracutaneous features.

It follows a more aggressive course than typical MF.

Slide 42 · Generalized exfoliative erythroderma

Mycosis fungoides

Patches / plaques / sometimes tumors

Often initially localized to skin

Stepwise but overlapping cutaneous phases

Sézary syndrome

Diffuse exfoliative erythroderma

Extensive skin involvement at presentation

Often accompanied by blood and nodal disease

Slide 43 · Generalized lymphadenopathy in Sézary syndrome

Skin erythroderma

Generalized nodes

Systemic phenotype

Generalized lymph node enlargement is part of the characteristic clinical syndrome.

This finding marks involvement beyond the skin compartment.

Consider the nodes together with erythroderma and leukemic cells.

Slide 44 · Leukemic peripheral blood involvement

Sézary syndrome includes circulating malignant T cells detectable in peripheral blood.

This as a leukemia of Sézary cells.

Overt blood involvement distinguishes its clinical phenotype from the indolent skin-dominant MF course.

Compartment distinction

MF: Subclinical circulation is possible.

Sézary syndrome: Leukemic blood disease is evident.

Slide 45 · Sézary cells have folded nuclear membranes

Circulating Sézary cells characteristically show cerebriform nuclei.

The convoluted nuclear contour parallels the morphology of cutaneous malignant T cells.

Blood morphology is one component of the characteristic clinical triad.

Marked nuclear membrane infolding

Schematic illustration — not a clinical or histologic specimen

Slide 46 · Tumefaction is unusual in Sézary syndrome

MF tumor progression

Cutaneous nodules can develop

Tumors may ulcerate

Deeper dermal growth

Sézary presentation

Diffuse erythroderma predominates

Tumefaction is uncommon

Blood/nodal disease prominent

Slide 47 · Three affected compartments in Sézary syndrome

Skin: Erythroderma

Blood: Leukemic T cells

Nodes: Generalized enlargement

Slide 48 · MF versus Sézary syndrome: Core discrimination

Dimension

Mycosis fungoides

Sézary syndrome

Presentation

Patches → plaques → tumors

Generalized exfoliative erythroderma

Tumor nodules

Can become prominent

Rarely develops tumefaction

Blood involvement

Occult circulation can occur

Overt Sézary-cell leukemia

Lymph nodes

Overt spread typically late

Generalized lymphadenopathy characteristic

Course

Usually relatively indolent

More aggressive

Slide 49 · Typical course of mycosis fungoides

MF generally develops over a long interval.

Cutaneous disease may remain the dominant problem for years.

A median survival of roughly 10 years (textbook-level estimate).

Do not overgeneralize

Prognosis is heterogeneous.

Skin extent and nodules alter risk.

Slide 50 · Skin surface area matters to prognosis

Affected surface area

Disease extent

Prognostic assessment

The percentage of body surface area affected contributes to prognosis.

Greater extent reflects more widespread cutaneous disease.

The supplied source does not provide stage cutoffs for body surface area.

Slide 51 · Tumor nodules indicate more aggressive disease

Development of cutaneous tumor nodules is linked with worse prognosis.

Nodular disease may coincide with more extensive lymphoid infiltration.

The presence of nodules is clinically meaningful beyond lesion count alone.

Morphology → prognosis

Patch / plaque predominant

Vs. Nodular tumor phase

Slide 52 · Systemic spread changes the clinical outlook

Skin disease

Clinically apparent spread

Higher-risk course

Nodal or visceral involvement is an adverse event during MF progression.

Tumor nodules and systemic spread are associated with aggressive disease.

The distinction between molecular circulation and overt spread remains important.

Slide 53 · Transformation to an aggressive T-cell lymphoma

Transformation of MF to an aggressive T-cell lymphoma can occur.

Robbins characterizes this as an occasional terminal event.

Do not equate every tumor-phase skin nodule with proven transformation.

Important distinction

Tumor-phase cutaneous progression

≠ necessarily aggressive transformation

Slide 54 · Sézary syndrome has a more guarded prognosis

MF: General course

Often prolonged skin-limited period

Median survival roughly 10 years

Prognosis worsens with extent/spread

Sézary: General course

Blood, nodes and erythroderma at presentation

More aggressive natural history

Fewer patients survive five years description

Slide 55 · Risk assessment is multidimensional

Dimension

Why it matters

Cutaneous extent

Percent of body surface involved correlates with prognosis

Cutaneous tumor nodules

Associated with greater aggressiveness

Clinically overt extracutaneous spread

Signals systemic progression

Syndromic presentation

Sézary syndrome differs from typical MF in course

Slide 56 · Early lesions: Skin-directed treatment

Early skin lesions

Skin-directed therapy

Steroids or UV light

Topical corticosteroids are used for early cutaneous lesions.

Ultraviolet light treatment is another described option.

These therapies in the context of early skin disease, not advanced systemic involvement.

Slide 57 · Advanced disease: Systemic treatment considerations

Advanced disease

Systemic approach

Chemotherapy (textbook)

Systemic chemotherapy for advanced CTCL disease.

The trigger for changing approach is disease advancement beyond early skin lesions.

Specific regimens and current guideline hierarchies are not covered in the supplied excerpt.

Slide 58 · Therapy follows anatomic and clinical burden

Earlier localized disease

Skin-dominant clinical pattern

Topical corticosteroids

Ultraviolet light

Advanced disease

Deep tumor / systemic involvement

More aggressive treatment approach

Systemic chemotherapy

Slide 59 · Case 1: A chronic erythematous patch

Illustrative patient: Persistent scaly, red-brown patch on the trunk.

Early eruption has an eczema-like clinical appearance.

Biopsy description: Atypical superficial dermal T-cell infiltrate with epidermal migration.

Question: Which disease and phase best fit?

Illustrative teaching vignette; Not a source patient record

Slide 60 · Case 1: Interpret clinical and microscopic clues

Mycosis fungoides—early patch / premycotic phase—is the most consistent pattern.

Clinical mimicry explains why initial appearance can be misleading.

Epidermotropism connects the lesion to the characteristic MF architecture.

Epidermis

Superficial dermis

Schematic illustration — not a clinical or histologic specimen

Slide 61 · Case 2: Plaques progress to a nodule

Illustrative patient: Longstanding scaly plaques become raised and indurated.

A cutaneous nodule subsequently develops.

Biopsy of the nodule shows deeper dermal lymphoid growth with less epidermotropism.

Question: Which feature indicates progression?

Illustrative teaching vignette; Not a source patient record

Slide 62 · Case 2: Progression does not require epidermotropism

Tumor-phase MF is favored by the nodular clinical lesion and deep dermal pattern.

Epidermotropism can decrease in advanced nodules.

Tumor nodules justify concern about more aggressive disease and spread.

Deep dermal tumor mass

Epidermis

Superficial dermis

Schematic illustration — not a clinical or histologic specimen

Slide 63 · Case 3: Erythroderma plus abnormal blood cells

Illustrative patient: Generalized exfoliative erythroderma.

Generalized lymphadenopathy accompanies the skin eruption.

Blood film reveals atypical T lymphocytes with markedly folded nuclear outlines.

Question: Which T-cell neoplasm unifies all three sites?

Illustrative teaching vignette; Not a source patient record

Slide 64 · Case 3: The defining triad identifies Sézary syndrome

Erythroderma

Lymphadenopathy

Sézary-cell leukemia

Diffuse erythroderma + generalized nodes + leukemic Sézary cells.

The presentation is systemic from the clinical standpoint.

It is not simply the ordinary plaque-to-tumor progression of MF.

Slide 65 · A clinicopathologic reasoning map

Cutaneous pattern

Skin histology + T-cell clonality

Blood / nodal assessment

Slide 66 · Summary: Morphology that carries diagnostic meaning

Patch and plaque MF: Epidermotropic atypical T cells + superficial dermal infiltrates.

Pautrier microabscesses: Intraepidermal groups of malignant lymphocytes.

Tumor-phase MF: Deep dermal growth; Epidermotropism may be lost.

Sézary syndrome: Cerebriform leukemic lymphocytes accompanying erythroderma.

Slide 67 · Summary: Two distinct clinical trajectories

Mycosis fungoides

Long cutaneous course

Patches → plaques → nodules

Clinical dissemination mainly later

Sézary syndrome

Diffuse exfoliative erythroderma

Blood and node involvement

Generally more aggressive

Slide 68 · Principal references

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. Elsevier; 2026. Chapter 13, pp. 551–552.

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. Elsevier; 2026. Chapter 25, pp. 1044–1045.

Clinical descriptions, molecular observations and prognosis are interpreted within the supplied textbook scope.