Classic MF

Classic MF, also known as Alibert–Bazin type of MF, is the most reported type of this CTCL¹,²,⁶. It represents about 90% of all MF cases and accounts for approximately 4% of all non-Hodgkin lymphomas²,⁶.

Males are more frequently affected⁹, typically adults in their 5th-6th decade⁹.

It is classified into three stages that include patch, plaque, and tumor stages⁶. Asymmetric telangiectasias and erythematous macules are the clinical manifestations of patch-stage MF⁶, which typically involves sun-protected areas like the breast (in female patients), buttocks, and trunk and extremities⁶. The plaque stage is usually characterized by erythematous, reddish- brown, or scaling lesions⁶. The last stage is characterized by nodules ≥ 1 cm⁶.

The stage of classic MF determines its prognosis⁹. Early-stage patients have an excellent prognosis and a survival rate comparable to that of age, sex, and race-matched individuals⁹, whereas advanced-stage patients over 60 years old are considered with a poor prognosis⁹. Anyway, most MF patients have a slow clinical progression over years or decades⁹.

The histopathological hallmark in the patch stage is the proliferation of large pleomorphic lymphocytes at the dermal-epidermal junction, focal parakeratosis, and papillary dermis fibrosis⁶. The plaque stage highly resembles the patch stage and reveals intersurface vascular changes like infiltration of the upper dermis by lymphocytes, which characteristically have hyperchromatic nuclei and nuclear membranes which are convoluted, in addition to Pautrier's microabscesses⁶. Neoplastic lymphocytes are widely distributed throughout the dermis in dense sheets at the tumor stage⁶.

Many disorders can be considered differential diagnoses of classic MF, such as perioral dermatitis, seborrheic eczema, palmoplantar eczema, dyshidrotic eczema, atopic eczema, contact dermatitis, tinea corporis, tinea pedis, psoriasis, and parapsoriasis¹⁰.

Hypopigmented MF

Hypopigmented MF is an uncommon clinical variant characterized by hypopigmented-to-achromic papules and macules without atrophy, sometimes with vitiligo-like lesions, in addition to patches ranging from small-size to large-size lesions⁸,¹¹.

Hypopigmented MF can be the only MF manifestation or coexist with classic MF lesions or other variants⁴. Lesions are mainly distributed on the trunk, extremities, and buttocks and may be associated with pruritus¹¹.

Hypopigmented MF is considered one of the commonly reported variants in children, although cases have been reported in adults too⁸. Dark-skinned individuals and Asians are commonly affected by hypopigmented MF⁴,⁸. Despite it is believed to have no gender predilection, some studies observed remarkable female predominance¹¹.

The prognosis is typically excellent, at least compared to classic MF¹¹.

Hypopigmented MF lesions are indistinguishable histopathologically from classic MF⁴. Some of the most common features include focal parakeratosis, lymphocytic infiltration in the upper dermis, slight or no spongiosis, and a variable number of lymphocytes at all levels of the viable epidermis disposed of as single units and episodically in small collections¹¹. Pautrier microabscesses are rarely observed¹¹. Other features involve slight psoriasiform epidermal hyperplasia, vacuolar alteration of the dermal-epidermal junction mimicking an interface dermatitis, scattered dyskeratotic keratinocytes, folliculotropism, and melanin incontinence associated with melanophages in the papillary dermis¹¹.

The differential diagnoses may include sarcoidosis, atopic dermatitis, leprosy, pityriasis alba, pityriasis versicolor, pityriasis lichenoides (PL) chronica, vitiligo, syphilis and other treponematoses, lichen sclerosus, postinflammatory hypopigmentation, idiophatic guttate hypomelanosis, onchocerciasis, hypomelanosis of Ito, and halo nevus¹¹.

Erythrodermic MF (EMF)

In erythrodermic MF (EMF), patients with the classic histopathologic findings of MF develop generalized erythroderma but with no diagnostic criteria of Sézary syndrome (SS), namely with the absence of blood involvement typical of SS²,⁸,¹². Additionally, they have a lower occurrence of lymphadenopathy¹². Anyway, SS is the main differential diagnosis of EMF⁸.

Generalized erythroderma is considered a progression of typical patch or plaque lesions of classic MF, but in some cases, erythroderma arises de novo²,¹². Pruritus is often present, and in rare cases, it may occur before the onset of the skin eruption¹².

Patients with EMF and Sézary syndrome had a poor overall prognosis¹², very particularly patients with erythroderma who have skin tumors¹².

Histopathological findings of EMF reveal classic features of MF with absent or a low amount of circulating neoplastic lymphocytes². However, epidermotropism is not present in some EMF cases¹².

Papular MF and pityriasis lichenoides-like MF

Pityriasis lichenoides-like MF (PL-like MF) is rare and occurs as a distinct variant of MF with a good prognosis presenting as localized or widespread erythematous scaly papules but without spontaneous regression of the lesions compared to PL⁴,¹³,¹⁴. PL-like MF is commonly reported in young patients and less in adults and children⁴,¹³.

Papular MF was primarily characterized in 2005 based on criteria including papules with histopathologic features of MF, spontaneous regression of lesions, and no additional evidence of lymphomatoid drug reaction or MF⁴. The prognosis is good in case there was no previous history of patches or any other clinical characteristics of MF; otherwise, the prognosis is bad if there is a previous history of patches or clinical features of MF¹³.

Papular MF lesions are presented as chronic and papular eruptions mainly located on the trunk and limbs with symmetric distribution¹³.

The histopathological findings of PL-like MF resemble both findings of MF (haloed lymphocytes, lymphocytes aligned along basal cells, Pautrier's microabscess, stuffed lymphocytes in the dermal papilla, coarse collagen bundles in the papillary dermis, and intraepidermal lymphocytes larger than dermal lymphocytes) and of PL (erythrocyte extravasation, spongiosis, necrotic keratinocytes, and exocytosis of lymphocytes and neutrophils)¹³. However, MF is distinguished from PL by the presence of epidermotropism and numerous atypical lymphocytes¹⁴.

The histopathological findings of papular MF do not comprise PL findings (such as necrotic keratinocytes or erythrocyte extravasation)¹³.

The differential diagnoses of PL-like MF include papular MF, PL, and lymphomatoid papulosis¹³, and the differential diagnoses of papular MF include, PL, lymphomatoid drug eruption, lymphomatoid papulosis type B, and persistent arthropod bite reactions⁴.

Unilesional MF

Unilesional MF, also known as solitary MF, presents as an isolated erythematous scaly patch or plaque generally located in sun-protected areas¹⁵,¹⁶. Lesions grow slowly and may be present for several years without confirming the diagnosis⁴,¹⁶. An excellent prognosis has been reported in previous studies⁷.

Unilesional MF is indiscernible histopathologically from the classic MF (patch and plaque-stage)⁷, but generally, atypia is more notable in the epidermotropic lymphocytes compared to those in the dermis⁷.

Unilesional follicular MF is a possibly curable form distinguished by neoplastic lymphocyte infiltration into the follicle¹⁷.

The main differential diagnosis of unilesional MF includes Bowen's disease, papulosquamous or eczematous lesions, and dermatophyte infection⁴.

Mycosis fungoides palmaris et plantaris (MFPP)

Mycosis fungoides palmaris et plantaris (MFPP) is a rare disorder expressed by erythematous hyperkeratotic patches or plaques with fissures and scales limited to palms or/and soles, often affected bilaterally, with or without itch, and without extracutaneous involvement⁴,¹⁸. This variant can occur in classical MF patients (about 10% of the cases)⁴.

MFPP commonly presents in middle-aged individuals (16–68 years; mean age 55 years)¹⁸, occasionally with pustular, vesicular, annular, verrucous, dyshidrotic, psoriasiform, hyperpigmented or ulcerative lesions, and nail dystrophy⁴.

Histopathological features are typical of MF, but spongiosis may be more distinct in MFPP, which makes it challenging to differentiate MFPP from spongiotic dermatitis⁴.

Differential diagnoses of MFPP may include palmoplantar psoriasis, hand eczema, contact dermatitis, hyperkeratotic lichen planus, secondary syphilis, dermatophytosis, and verrucae¹⁸.

Ichthyosiform MF

Ichthyosiform MF is uncommon and generally presents as dry, diffuse, and scaling skin with well-circumscribed scaly patches or flat plaques, with a pattern resembling ichthyosis vulgaris's cobblestones⁴,⁸. Lesions are typically located on the trunk and extremities and can be associated with other variants of MF, particularly FMF, or present only as ichthyosiform lesions⁴,¹⁹. It has an indolent course and a favorable prognosis, with a mean age of onset is around 32 years¹⁹.

Ichthyosiform MF reveals compact orthokeratosis, hypogranulosis, and a band-like epidermotropic infiltrate comprised of small cerebriform lymphocytes⁹.

Many differential diagnoses can be taken into account, including ichthyosis vulgaris, drug eruption, sarcoidosis, underlying malignancy (such as paraneoplastic eruption), and endocrinologic and autoimmune disorders⁴.

Vegetating/papillomatous MF

Vegetating/papillomatous MF, also known as acanthosis nigricans-like MF, is a rare variant of MF that presents as brownish or velvety hyperpigmented, polygonal plaques with varying patches of erythema between the lesions located on the neck, axillae, groin, popliteal fossae, intergluteal, nipple, areolae, and periumbilical areas⁴,⁹,²⁰. Some lesions may become more prominent and even nodular²⁰. Lesions may be itchy⁴,⁹,²⁰.

Histopathologic features of acanthosis nigricans-like MF include the typical features of MF in addition to acanthosis and papillomatosis together with a band-like infiltrate of atypical lymphocytes that may be epidermotropic or not⁴,²⁰. Interconnected rete pegs and horny pseudocysts with seborrheic keratosis-like features may be present⁴, which can mimic acanthosis nigricans or seborrheic keratosis based on their presentation, size, and color⁹.

Erythema annulare centrifugum (EAC) and erythema gyratum repens (EGR)-like MF

Many cases of MF with annular or polycyclic erythematous patches and/or plaques have been reported in the literature²¹. EAC-like MF is characterized by trailing scales and erythematous concentric rings, which expand outward without central clearing²¹, whereas EGR-like MF lesions are also characterized by symmetrically distributed red patches with erythematous concentric rings and trailing scales⁴,²¹, but no evident central clearing, as the whole patch is comprised of band-like rings⁴.

Histopathologically, EAC-like MF has typical features of MF⁴ without the perivascular lymphocytic “coat-sleeve-like” infiltration typical of EAC⁴.

EAC-like MF may simulate Lyme disease, superficial fungal infection, and tinea imbricata⁴,²¹.

Invisible MF

Invisible MF is an extremely rare variant that presents with persistent and occasionally generalized pruritus as the only clinical manifestation²²-²⁵ but has the histopathologic findings of classic MF²²-²⁵, including occasional Pautrier microabscesses²³,²⁵.

Systemic amyloidosis, pseudoxanthoma elasticum, and pretibial myxedema has been reported in normal-looking skin, and they are considered differential diagnoses of invisible MF²².

Folliculotropic MF (FMF)

Folliculotropic MF (FMF) is the most common atypical clinicopathologic variant¹,⁴. It is classified as a clinicopathological variant by WHO-EORTC classification that clarifies the existence of follicle-based lesions and folliculotropism as the predominant histopathological characteristics, with or without follicular mucinosis⁴.

FMF diagnosis comprises idiopathic follicular mucinosis, even though it is discussed whether this represents universal FMF or a distinct entity, and another entity that is amalgamated with CTCLs such as SS, MF, adult T-cell leukemia, and lymphomatoid papulosis²⁶.

The clinical presentation of FMF includes various morphologies such as erythematous plaques, follicular papules, acneiform lesions, prurigo-like lesions, cysts, and patches of alopecia that can associate with eyebrow involvement and maybe with scarring⁶,²⁷,²⁸, in addition to other unusual presentations that include pseudotumors, rosacea-like lesions, lupus tumidus-like, and lichen spinulosus-like lesions in association with alopecia and hypopigmentation²⁸. Alopecia is a common and typical featured finding of FMF which is observed in up to 81% of patients²⁸. Lesions are located mainly on the upper trunk and extremities (in up to 73% of patients), neck, and face²⁷, very often reported as predilection locations²⁶. Leonine appearance is a rare expression of MF, which is associated with stage-IV CTCL and with blood and folliculotropism involvement during the disease progression²⁶,²⁷.

Difficult-to-manage pruritus is a common symptom in adult patients, but in contrast, children with FMF complain of mild pruritus²⁶. FMF mainly affects adults but has also been reported in adolescents and children with a male predominance⁴,²⁶.

Erythroderma also may manifest in up to 6% of FMF cases²⁶. 92% of patients have skin-restricted involvement, while 8% of them have visceral or nodal involvement at their first presentation²⁸. Secondary bacterial infections are commonly noticed in FMF patients¹.

FMF is characterized histopathologically by infiltration of atypical lymphocytes surrounding the hair follicles and generally spares the interfollicular epidermis and is occasionally accompanied by the follicle's disruption⁴,²⁷. A mild perivascular inflammatory infiltrate occurs in the upper dermis without evident lymphocyte atypia in the early stage²⁷,²⁸, and apart from follicles, infiltration can also affect eccrine sweat glands (syringotropism): adnexotropic MF¹. In addition, mucin degeneration of the follicular epithelium was typically reported in many cases¹,²⁷.

The most paramount histopathological differential diagnoses of FMF include pseudolymphomatous folliculitis, follicular lymphomatoid papulosis, and follicular eczema²⁶.

FMF diagnosis may be delayed, 18–48 months on average, after the lesion onset due to its distinct clinical presentation of classic MF²⁶,²⁸.

Recent studies classified an early-stage FMF with a good prognosis and a more aggressive advanced-stage FMF subgroup²⁶, which has a poor prognosis with a 5-year surviving rate of 70–80%²⁷. The survival range of tumor FMF is similar to classical tumor-stage MF⁴. Reduced survival has been linked to large cell transformation, advanced age, and broad secondary bacterial infection¹.

Differential diagnoses depend upon the various clinical presentations of FMF⁴. Erythematous lesions on the scalp can be misdiagnosed as psoriasis capitis, atopic dermatitis, and seborrheic dermatitis⁴. Alopecia on the scalp can mimic trichotillomania, cicatricial alopecia, and alopecia areata⁴. Rosacea, adult-onset acne, follicular- comedogenic graft-versus-host disease, chloracne, and Favre-Racouchot syndrome have to differentiate from acneiform lesions⁴. Pityriasis rubra pilaris, lichen spinulosus, lichen planopilaris, and keratosis pilaris should be taken into account as differential diagnoses in follicular spiky papules⁴. In addition, alopecia mucinosa should be considered as a differential diagnosis in hairless patches and/or plaques⁴.

Bullous and vesicular MF

Bullous and vesicular MF, also known as vesiculobullous MF lesions, are rare and aggressive variants of MF that can occur on normal-appearing skin and/or on the affected skin with classic MF/SS⁴,²⁹. Vesiculobullous MF lesions usually manifest as multiple flaccid or tense bullae on the trunk and proximal limbs with a predisposition to form ulcers⁴,⁶,²⁹,³⁰. The lesions have a poor prognosis and mostly affect older people without gender predominance²⁹.

Has been reported; an association between bullous MF, bullous pemphigoid, former treatment with psoralen plus ultraviolet A, topical mechlorethamine, or/and systemic interferon⁴,²⁹. In addition, it is very probable that vesicular MF can onset on the affected skin with atopic diathesis⁵.

The histopathological mechanism underlying blister formation has not been demonstrated²⁹. The confluence of malignant lymphocytes within the epidermis causes the secession of the epidermis from the dermis⁵.

Vesiculobullous MF lesions are expressed by intraepidermal or subepidermal blisters combined with classic findings of MF like atypical lymphocytes, epidermotropism, and the aggregation of Pautrier's microabscesses⁵,⁸,²⁹.

Bullous MF can mimic many disorders, including autoimmune bullous disorders (bullous pemphigoid, bullous lichen planus, bullous lupus erythematosus, and pemphigus vulgaris), porphyria, drug eruptions, and viral infections⁴,⁶,²⁹. Besides, vesicular MF should be differentiated from autoimmune bullous disorders, eczematous dermatitis, bacterial or viral infections, and drug eruption⁴. However, vesiculobullous MF lesions are distinguished from blistering autoimmune diseases by their negative direct and indirect immunofluorescence results⁸.

Poikilodermatous MF

Poikilodermal MF, also known as poikiloderma vasculare atrophicans, is a variant of MF, that is characterized by cutaneous atrophy, macular pigmentary changes, mild scaling, and telangiectasia⁴,⁸,³¹. It is usually considered a clinicopathologic variant of patch-stage classic MF⁴.

Poikilodermal MF manifests as small plaques or papules, usually asymptomatic or mildly pruritic, ordered in a net-like pattern at the onset of the lesions, then the lesions usually develop into large plaques or affect the skin generally³¹. However, the lesions are typically either stable or slowly expanding³¹.

The most common locations of poikilodermatous MF are the breast (in women) and buttocks (in both women and men)⁸. The skin of the patient may resemble “cigarette paper” as a result of atrophy and thinning³¹.

Poikilodermatous MF has been reported in children with a higher percentage compared to adults¹⁵. Also, there have been reports of progression from poikilodermal MF in childhood to EMF in adulthood¹⁵. Anyhow, the prognosis of poikilodermal MF is favorable, and it responds to phototherapy⁸.

Histopathologically, poikilodermal MF shows an atypical T-cell infiltrate in the papillary dermis, often with obvious epidermotropism³¹. In addition, melanophages and melanin incontinence are present, associated with ectasia of the superficial dermal vessels and epidermal atrophy³¹. Pautrier microabscesses are not typically present⁸.

Morphea, lichen sclerosus, ashy dermatosis, and radiation dermatitis are considered differential diagnoses of poikilodermal MF⁴.

Pagetoid reticulosis (PR)

Pagetoid reticulosis (PR), also known as Woringer-Kolopp disease, is a rare variant of MF occurring both in children and adults⁴,⁶. It typically manifests as a slowly progressive, solitary, hyperkeratotic or psoriasiform patch or plaque with a well-defined elevated border and a central clearing that usually affects the limbs, especially the feet and hands¹,⁶. In some cases, ulceration and pain were also reported⁶.

PR has an excellent prognosis with no disease-related deaths or extracutaneous involvement¹.

However, PR may progress to a disseminated PR or Ketron-Goodman disease, which currently corresponds to a more aggressive form of cutaneous lymphoma (epidermotropic cytotoxic T-cell lymphoma in almost all reported cases)⁸.

Typical histopathologic findings of PR include epidermal hyperplasia and marked infiltration by small to medium-sized atypical pagetoid cells, ordered separately or in nests or clusters¹. Atypical cells consist of medium to large-sized cerebriform nuclei with abundant, vacuolated cytoplasm¹. Neoplastic T-cells are rarely observed in the superficial dermis, but an infiltration mostly of small lymphocytes can occur¹.

The differential diagnoses of PR may involve psoriasis, chronic dermatitis, verrucous squamous cell carcinoma, tuberculosis verrucosa cutis, and blastomycosis⁴.

Mycosis fungoides (MF) with eruptive infundibular (epidermoid) cysts

Some MF patients have reported having a localized or generalized follicular eruption with comedones and infundibular cysts, which appears to be a rare variant of MF⁸. This form combines MF with multiple, tiny, and eruptive epidermoid cysts and comedones³². Keratinous cysts can occur on uninvolved skin or on MF patches and plaques³². Some lesions have an acne-like or comedo-like manifestation³². Lesions may occasionally resemble tumor-stage lesions due to their size and inflammatory appearance⁸.

MF with eruptive infundibular cysts needs to be differentiated from FMF, although some authors consider these two variants are part of the same spectrum with follicular involvement in MF⁸. Also, Favre-Racouchot disease should be considered as a differential diagnosis if MF with eruptive infundibular cysts lesions are located on the face³².

Histopathology shows the characteristic features of an infundibular cyst encompassed by a dense infiltrate formed mainly by atypical lymphocytes in the cyst wall⁸. Infundibular cysts may be associated with the infiltration of follicular openings by neoplastic cells, causing expansion of the infundibula and subsequent blockage⁸.

Syringotropic MF (STMF)

Syringotropic MF (STMF) is a rare variant of MF characterized by eccrine sweat gland infiltration¹,⁴. It is also called syringotropic CTCL, syringolymphoid hyperplasia with alopecia, or adnexotropic T-cell lymphoma⁴. STMF features imbricate with FMF and, therefore, it was classified as a subtype of FMF within the WHO-EORTC classification⁴, but differences in survival between STMF and FMF in a recent study suggested they should be categorized separately³³. STMF is much less aggressive than FMF³⁴.

STMF is usually located in sun-protected areas with a tendency to affect males twice as often as females, with a mean age of 55⁴,³⁴. It presents as a solitary lesion or numerous erythematous patches, papules, or plaques with dotted follicular accentuation, in addition to overlying alopecia, which is reported commonly in STMF⁴,³⁴. Also, hypohidrosis is periodically observed in STMF³⁴.

STMF demonstrates histopathological features, including hyperplasia of eccrine glands and ducts encompassed and penetrated by dense infiltration of atypical lymphocytes in the dermis³⁴.

The differential diagnoses of STMF involve perniosis, neutrophilic eccrine hidradenitis, classic MF, and syringometaplasia without a significant lymphocytic infiltrate, as in post-chemotherapy, ischemia, and radiation dermatitis³⁵.

Granulomatous slack skin (GSS)

Granulomatous slack skin (GSS) is a very rare clinicopathologic variant of MF that shares histopathological characteristics with granulomatous MF (GMF), which makes it difficult to differentiate it from this variant¹,⁶. It is more common in younger people⁶.

Initial cutaneous lesions in GSS have a similar presentation to classic MF, including patches and plaques¹. Then GSS lesions develop into large and pendulous folds of atrophic skin, due to the loss of elastic fibers, in locations such as groins and axilla (flexural areas) resembling cutis laxa¹,². Extracutaneous involvement of GSS is uncommon⁶. Hodgkin lymphoma or nodal non-Hodgkin lymphoma has been reported as an associated disease in 30–50% of GSS cases².

GSS is manifested by a slow and indolent advanced clinical course¹. However, the complete recovery of GSS has never been reported¹.

Histopathology of GSS includes multinucleated giant cells (comprising > 10 nuclei for each cell) in addition to elastophagocytosis, emperipolesis (engulfment of lymphocytes), and loss of elastic tissue¹. The infiltration by small atypical T-cells with cerebriform nuclei in the epidermis may be observed, as in the classic MF¹.

It is necessary to take into account differential diagnoses such as infectious granulomas, sarcoidosis, granuloma annulare, and anetodermic MF (AMF)³⁶,³⁷.

Hyperpigmented MF

Hyperpigmented MF is a very rare variant of MF classified as an unusual clinical manifestation of palmaris et plantaris MF and presents clinically as hyperpigmented macules, patches, and/or plaques without the presence of poikilodermatous changes⁴,⁸,³⁸. Some cases manifest with indistinct borders and diverse degrees of skin atrophy and scaling⁴.

Although some patients may present with associated lesions of classic MF or other MF variants, hyperpigmented MF may be the only manifestation of MF⁴.

Hyperpigmented MF typically affects people with dark skin and younger ages (under 35 years old), and it has slowed clinical progression³⁸. Anyhow, it has a better prognosis compared to classic MF³⁸.

Histopathologically, in addition to findings of classic MF, diffuse vacuolar degeneration of basal keratinocytes imitating “interface dermatitis”, along with melanophages, have been observed in the most hyperpigmented MF cases⁴.

Many disorders should be considered as differential diagnoses of hyperpigmented MF, including pigmented contact dermatitis, cutaneous amyloidosis, fixed drug eruption, post-inflammatory hyperpigmentation, idiopathic eruptive macular hyperpigmentation, atrophoderma of Pasini and Pierini, and erythema dyschromicum perstans⁴.

Anetodermic MF (AMF)

Anetodermic MF (AMF) is a cutaneous disorder characterized by progressive loss of dermal elastic tissue, which results in atrophic plaques with a featured parchment-like surface⁸. The most involved locations are limbs, face, buttocks, and trunk³⁷.

Primary anetoderma occurs when there is no underlying associated disease, and it arises on clinically normal skin, whereas secondary anetoderma appears on the same site as a prior specific skin lesion³⁷. However, the appearance of AMF in classic MF lesions is extremely rare⁸.

Histopathologically, T-helper lymphocytes are infiltrated into the dermis with a few histiocytes and some multinucleate large cells engulfing deformed elastic fibers³⁷. In the dermis, elastic fibers are almost completely absent³⁷.

GSS is the main differential diagnosis of AMF³⁷.

Verrucous MF

Verrucous MF is a quite rare variant of MF which presents as warty, hyperkeratotic, pruritic plaques that can be located on the trunk, face, and limbs and can be associated with classic MF lesions⁴.

Verrucous MF lesions may manifest as single or many erythematous papules that progressively enlarge and become more raised with a verrucous surface³⁹. Apart from pruritus, most verrucous MF lesions are asymptomatic³⁹.

Location on the extremities was commonly reported in African-Americans with a history of long-standing MF³⁹. It has been noticed that African-American women are more likely to develop early-onset MF with a poor prognosis³⁹.

Histopathologic characteristics of verrucous MF involve classic MF findings along with hyperkeratosis and papillomatosis, inflammatory infiltration into the papillary dermis, and exocytosis and spongiosis in the epidermis⁸.

Many disorders can be assumed as differential diagnoses, such as verrucae vulgaris, keratoacanthoma, palmoplantar hyperkeratosis, seborrheic keratosis, porokeratosis of Mibelli, and inflammatory linear verrucous epidermal nevus⁴.

Psoriasiform MF

Psoriasiform MF is a rare variant of MF considered an unusual clinical manifestation of palmaris et plantaris⁴,⁴⁰.

The clinical presentation of psoriasiform MF involves scaly, well-defined, thick, erythematous psoriasiform plaques, which can mimic psoriasis⁴. Additional alopecia, induration, erosions, and ulcerative lesions may occur in some patients⁴. However, many cases reported generalized lesions⁴⁰,⁴¹.

The majority of reported cases were in males, with a mean age of 54 years⁴¹.

Histopathological findings are characterized by epidermotropism of atypical lymphocytes⁴⁰. Scant spongiosis and a lichenoid pattern have also been reported⁴. In addition, histopathologic findings of psoriasis, including elongation of the rete ridges with regular acanthosis, thinning, parakeratosis with hyperkeratosis, or Munro microabscesses and total effacement of the granular layer are present⁴².

The clinical differential diagnoses of psoriasiform MF include psoriasis vulgaris, lichen planus, lichen simplex chronicus, leprosy, and ashy dermatosis⁴⁰.

Dyshidrosis-like vesicular eruption (DLVE)

Dyshidrosis-like vesicular eruption (DLVE) is an extremely rare variant of MF³⁰. It presents as vesicles restricted to palms and soles with a possible expansion to the trunk and extremities, but there have been no reported cases of extracutaneous involvement³⁰. DLVE has been reported in association with adult T-cell lymphoma/leukemia³⁰.

The microscopic sections show typical features of MF, including cerebriform lymphocytes, epidermotropic lymphocytes, and Pautrier microabscesses³⁰. In addition, lymphokines released by neoplastic T-cells might obstruct normal keratinocyte adhesion³⁰. Immunofluorescence studies of DLVE are negative, but acantholysis may occur³⁰.

Contact dermatitis, atopic eczema, and palmoplantar eczema are considered differential diagnoses of DLVE⁶.

Pigmented purpuric dermatosis (PPD)-like MF

Pigmented purpuric dermatosis (PPD)-like MF is considered a rare variant of MF⁴. It is usually reported in children and adults with a male predilection⁴,⁴³. PPD-like MF is characterized by golden-brown discoloration and enduring purpuric lesions⁴. It can mimic chronic pigmented purpura clinically⁴. The most common location of PPD-like MF is the lower extremities, with a rare possibility of a generalized involvement⁴³. The histopathological examination of PPD-like MF reveals similar characteristics of MF, besides extravasation of erythrocytes in the papillary dermis with the presence of siderophages⁴.

Pustular MF

Pustular MF is a very rare variant of MF which is considered an unusual manifestation of palmaris et plantaris MF⁴. It is characterized as a persistent vesicular pustular eruption that gradually transforms into typical MF plaques⁸. Anyway, the pustular MF lesions can be generalized or restricted to the palmoplantar location⁸.

Histopathology reveals typical MF findings, such as epidermotropism, band-like infiltration of atypical lymphocytes, and Pautrier microabscesses, in amalgamation with neutrophils, eosinophils, subcorneal pustules containing atypical lymphocytes⁸.

Pustular psoriasis, drug reaction, and skin infections are considered differential diagnoses of pustular MF⁴.

Granulomatous MF (GMF)

Granulomatous MF (GMF) is a histopathological variant of MF that may be diagnosed at the time of its first onset or years later⁴. It may manifest clinically as papules, plaques, or ulcerated nodules, without the characteristics of a cutis laxa-like that are typical of GSS⁴,⁴⁴. GMF occurs more frequently in males in their 5th and 6th decades of life⁴⁴.

GMF progresses frequently and is associated with a high risk of developing a second lymphoma⁸. In addition, its prognosis is poorer than classic MF⁸.

The EORTC's histopathologic criteria for GMF involve a histiocyte-rich infiltrate with histiocytes accounting for > 25% of the whole infiltrate, prominent granuloma formation, or a large number of histiocytic giant cells⁴. GMF has a variety of histopathologic patterns, including epithelioid, sarcoidal, palisaded, periadnexal, tuberculoid, necrobiotic granuloma-like, granuloma annulare-like, and diffuse granulomatous infiltrate⁴.

Although GMF is clinically distinct from GSS, histopathologic examination reveals a decreased portion of multinucleated cells⁸. Epidermotropism is typically not a prominent feature². Also, elastophagocytosis is a rare finding, but the loss of elastic fibers is common⁴.

The differential diagnoses of GMF include lipoid necrobiosis, annular granuloma, granulomatous panniculitis, and granulomatous rosacea⁴⁴.

Interstitial MF

Interstitial MF lesions are a rare histopathologic manifestation of MF, with a persistent cytotoxic phenotype⁴⁵. Patches and plaques are the typical clinical exhibition of interstitial MF, which can arise at any location of the body, in addition to atrophy and lack of scales⁴,⁴⁵,⁴⁶. The lesions can also present as erythematous patches surrounding the nasolabial folds and small papules located on the chin, which are called perioral dermatitis-like lesions⁴⁷.

Histopathologically, distinguishing features of interstitial MF include lymphocytes infiltrating the dermis and dissecting the collagen bundles⁴. Epidermotropic lymphocytes present focally in many cases⁴. Additionally, mucin deposition may present in the dermis⁸. However, the histopathological features of interstitial MF correspond to the interstitial variant of granuloma annulare⁴⁸.

The main differential diagnoses of IMF include interstitial granuloma annulare, interstitial granulomatous dermatitis, and the inflammatory stage of morphea⁴,⁴⁵. Moreover, the differential diagnoses regarding perioral dermatitis-like lesions include contact dermatitis, seborrheic eczema, and atopic eczema⁶.

Mycosis fungoides (MF) with large-cell transformation (LCT)

The development of large T-cell lymphoma from MF is classified as a histopathologic variant of MF which is described as the exhibition of large cells (> 4 times the size of a small lymphocyte) in at least 25% of the dermal infiltrate or forming microscopic nodules in which large cells that are either CD30⁺ or CD30^−8,49.

Mycosis fungoides (MF) with large-cell transformation (MF-LCT) is commonly present with a poor prognosis and arises in 20-50% of advanced MF⁵⁰. However, it occurs more frequently in tumor-stage MF patients⁸.

MF-LCT must be differentiated from other essential cutaneous lymphomas with CD30⁺ large cells, like lymphomatoid papulosis and anaplastic large-cell lymphoma⁸. Anyway, the prognosis for MF-LCT is poor, while the prognosis for cutaneous anaplastic large-cell lymphoma is excellent⁴⁹.

Epidermal hyperplasia and dermal fibrosis at transformation were linked to longer survival⁵⁰. On the other hand, the shorter survival appears to be correlated with a clinically advanced stage at transformation, older age, and serum lactate dehydrogenase of > 220 U/L⁵⁰. A recent study suggests that patients with MF who have CD30⁺ large-cell tumors have a better prognosis than those with CD30⁻ large-cell tumors⁴⁹.

A summary of the most involved locations, clinical presentations, and differential diagnoses of MF variants are demonstrated in the following (Table 2)¹,²,⁴-¹³,¹⁵,¹⁶,¹⁸-⁴⁷.