Cutaneous T-Cell Lymphoma Clinical Presentation

Updated: Jun 23, 2017
  • Author: Lauren C Pinter-Brown, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Presentation

History

The skin rash of mycosis fungoides may consist of patches, plaques, or tumors, which may have a long natural history. The median duration from the onset of skin symptoms to diagnosis is 6 years. Early in the course of mycosis fungoides, as well as in erythrodermic cases, the skin lesions may be nonspecific, with a nondiagnostic biopsy result, so that confusion with benign conditions is common (eg, eczema, neurodermatitis, pseudolymphoma syndrome). Obtain repeated biopsies in patients who have progressive chronic dermatosis or whose condition is refractory to topical treatments.

In patients who present with pruritus or erythroderma, the diagnosis of mycosis fungoides is often made possible through the examination of a noncutaneous site (eg, blood, lymph nodes).

Classic mycosis fungoides

Classic mycosis fungoides is divided into 3 stages: patch (atrophic or nonatrophic), plaque, and tumor. Often, the first stage goes on for many years and is characterized by a nonspecific dermatitis, which usually consists of patches and is often found on the lower trunk and buttocks. Sometimes, these patches have a thin, wrinkled quality, often with reticulated pigmentation. In this stage, pruritus is usually minimal or absent. [58]

Classic mycosis fungoides is usually preceded by a nonspecific, indolent inflammatory process manifesting as atopic dermatitis, nonspecific chronic dermatitis, or parapsoriasis (most commonly large-plaque parapsoriasis), which may progress over years to decades to early plaque-stage mycosis fungoides. Some regard large-plaque parapsoriasis as patch-stage mycosis fungoides. (See the images below.)

Plaque-stage parapsoriasis. Plaque-stage parapsoriasis.
Patch-stage mycosis fungoides progressing to plaqu Patch-stage mycosis fungoides progressing to plaque stage, with cutaneous cigarette-paper appearance evident.

In many cases, the disease never progresses beyond this stage, and the diagnosis of mycosis fungoides is never confirmed. In other cases, the disease appears from the beginning as rather well-defined, superficial plaques that range from 2 cm to more than 20 cm in greatest diameter. In children, early stage disease and unusual forms, such as the hypopigmented variant, tend to predominate. [59]

Stages IA and IB

While well-developed plaques that are clinically diagnostic for mycosis fungoides are usually intensely pruritic, less characteristic ones typically are not, and the development of pruritus in such lesions is a sign of progression towards mycosis fungoides. Depending on whether the lesions involve up to 10% of the body surface or involve 10% or more of the body surface, such cases are classified as stage IA or IB, respectively. Many cases remain at these stages for many years or decades without further progression.

Stages IIA and IIB

Clinical lymphadenopathy may develop (stage IIA), sometimes with progression of the plaques to form tumors (stage IIB), or tumors may form from plaques in the absence of lymphadenopathy (stage IIB). Either process usually takes years, or even decades, to develop. Once tumors form, they are prone to ulceration.

D'embleemycosis fungoides

The sudden multifocal development of tumors of apparent mycosis fungoides may rarely occur without preceding patches or plaques. Most, if not all, of such cases probably represent primary cutaneous CD30+ pleomorphic, medium or large cell T-cell lymphomas.

Stage III (erythrodermicmycosis fungoides)

Mycosis fungoides that is evident as an erythroderma but with too few circulating lymphocytes to warrant a diagnosis of Sézary syndrome is designated erythrodermic mycosis fungoides. Dermatopathic lymphadenopathy is present in these cases. Rarely, such patients may present with a nodulotumorous eruption. [60]

Stages IVA and IVB

Development of lymph nodes that are histologically positive for tumor (stage IVA) and/or visceral lesions (stage IVB) may occur rather rapidly after tumor-stage disease develops and/or clinical lymphadenopathy is detected. Alternatively, either or both may arise from erythrodermic disease (stage III) at a very variable rate. Both are associated with a poor prognosis.

Transformation ofmycosis fungoides

Mycosis fungoides in any stage may suddenly become much more aggressive, progressing rapidly to more advanced stages (see the images below). This is associated with the histologic appearance of large, atypical cells; often, these are CD30+, and the process is termed large cell transformation. It may be evident as a new, solitary nodule within a classic mycosis fungoides patch or plaque, as abrupt onset of multiple scattered papules and/or nodules without spontaneous resolution, or within new or enlarging tumors. [61]

Middle-aged woman with mycosis fungoides showing u Middle-aged woman with mycosis fungoides showing ulceration and marked depigmentation of advanced disease.
Middle-aged woman with mycosis fungoides showing u Middle-aged woman with mycosis fungoides showing ulceration and marked depigmentation of advanced disease.

Variants of mycosis fungoides

Pagetoid reticulosis

Pagetoid reticulosis arises preferentially on acral skin. The histologic hallmark of the disease is the pagetoid spread of haloed lymphoid cells in the epidermis.

Patients with localized pagetoid reticulosis are usually first seen with a solitary psoriasiform or hyperkeratotic patch or plaque, which is usually localized on the extremities; it is slowly progressive. In contrast to classic mycosis fungoides, extracutaneous dissemination and disease-related deaths rarely occur. (Ketron-Goodman disease, which is multilesional, has a clinical course similar to that of mycosis fungoides. Some cases may actually represent primary cutaneous epidermotropic CD8+ (cytotoxic) T-cell lymphoma.)

Folliculotropic mycosis fungoides

Folliculotropic mycosis fungoides is commonly first evident clinically with alopecia, follicular cysts, or comedolike lesions and is usually associated with follicular mucinosis and strong epidermotropism. [62] It is most commonly seen on the head and neck, often showing infiltrated plaques together with acneiform comedolike papules, epidermal cysts, and keratosis pilaris–like papules. [63] When mucin is present, the disease is also called alopecia mucinosa.

However, the benign form of alopecia mucinosa, which is not associated with mycosis fungoides, must be distinguished from mycosis fungoides associated with mucinosis. The most relevant feature, with and without associated follicular mucinosis, is the deep follicular and perifollicular localization of the neoplastic infiltrates, which makes them less accessible to skin-targeted therapies.

Hypopigmented mycosis fungoides

Hypopigmented mycosis fungoides tends to occur in young, slightly to moderately dark-skinned people of Indian, Latin American, or sub-Saharan African American heritage. It manifests as irregular, but fairly well-demarcated, hypopigmented or white patches. They are asymptomatic or are slightly pruritic and may appear with or without other lesions typical of mycosis fungoides. (See the images below.)

Hypopigmented cutaneous T-cell lymphoma. Courtesy Hypopigmented cutaneous T-cell lymphoma. Courtesy of Jeffrey Meffert, MD.
Hypopigmented cutaneous T-cell lymphoma. Courtesy Hypopigmented cutaneous T-cell lymphoma. Courtesy of Jeffrey Meffert, MD.

Pustular mycosis fungoides

A granulomatous reaction pattern occasionally is seen in mycosis fungoides and its variants. Pustular mycosis fungoides also can occur; it is often limited to the palms, but the lesions may occur elsewhere.

Bullous mycosis fungoides

Bullous mycosis fungoides manifests with flaccid, tense, or ruptured bullae arising on normal skin or an erythematous base or within typical patch- or plaque-stage lesions of mycosis fungoides. It tends to arise on the trunk and extremities. Rarely, it may clinically resemble pemphigus vulgaris or even erythema multiforme.

Hyperpigmented mycosis fungoides

Hyperpigmented mycosis fungoides is diffuse macular hyperpigmentation accompanied by typical mycosis fungoides, although in rare cases the hyperpigmentation may be the only manifestation. These lesions may resemble ashy dermatosis or may appear as more or less well-defined macules. Ultrastructural studies have revealed atypical lymphocytes and keratinocytes, macrophages, and Langerhans cells that contain giant melanosomes within lysosomes.

Unilesional mycosis fungoides

Unilesional mycosis fungoides manifests as a single area of otherwise typical mycosis fungoides that, by definition, manifests as a single lesion. Histologic changes are identical to those that occur with multiple disseminated lesions of mycosis fungoides. The prognosis is excellent following treatment, although it may recur after surgical excision.

Syringotropic mycosis fungoides

In addition to hair follicles, atypical cells in mycosis fungoides may rarely be tropic to eccrine glands. In the even rarer syringotropic mycosis fungoides (syringolymphoid hyperplasia), these are the principal or only lesions observed. The eccrine duct and the eccrine gland are typically involved and eccrine epithelium may appear hyperchromatic and atypical, mimicking eccrine carcinoma. Lesions manifest as red to skin-colored papules, red to brown patches, or red scaly plaques. Hair loss without mucinous degeneration in the affected areas is common. Most reported cases have been in men; in one series, only 4 of 14 patients were female. [64]

Poikilodermic mycosis fungoides

Poikilodermic mycosis fungoides occurs when poikiloderma (ie, poikiloderma vasculare atrophicans, which is a combination of atrophic, dry, dyspigmented skin and telangiectasia) develops in cases of otherwise typical mycosis fungoides; this is not an infrequent occurrence. Occasionally, it may predominate or even be the only presenting manifestation of the disease. It may rarely involve skin over the entire body.

Granulomatous slack skin syndrome

Granulomatous slack skin syndrome is a distinct subtype of mycosis fungoides that is characterized by ponderous, more-or-less infiltrated folds of skin that arise slowly in intertriginous areas, especially the axillae and groin. Granulomatous slack skin syndrome may give rise to Hodgkin disease.

Additional variants and characteristics

Other variants of mycosis fungoides include hyperkeratotic/verrucous and vegetating/papillomatous mycosis fungoides, typically arising in the axillae, perineum, and cervical area (neck), as well as, sometimes, on the breasts near the areolae, resembling acanthosis nigricans or multiple seborrheic keratosis.

Persistent, pigmented, purpuralike to lichenoid processes also may be a manifestation of mycosis fungoides.

Mucosal involvement by mycosis fungoides is rare and may occur as part of generalized involvement in advanced cases, particularly those that have undergone large cell transformation; it is a poor prognostic sign.

Sézary syndrome

The combination of erythroderma and leukemia is defined as Sézary syndrome. However, different clinicians use different criteria regarding the number of circulating atypical lymphocytes sufficient to warrant this diagnosis. According to some, the diagnosis is established in an erythrodermic patient if more than 5% of peripheral lymphocytes are atypical. Others use the absolute number of atypical lymphocytes in the peripheral blood (>1000/µL). In obvious cases, some use a quick and easy criterion of greater than 10 CD4+ T cells for every CD8+ T cell.

Lymphadenopathy is usually present, and the skin itself is usually edematous. Other frequently observed changes include palmar and/or plantar hyperkeratosis, alopecia, nail dystrophy, and ectropion. Hepatosplenomegaly may be present. As in other forms of mycosis fungoides, a nonspecific dermatitis and/or pruritus may precede the disease. Transformation of the disease to a more aggressive form is common. It may occur in lymph nodes even as skin lesions are showing improvement or a response to treatment.

Next:

Physical Examination

The following signs of cutaneous T-cell lymphoma are discussed in this section:

  • Patches and plaques
  • Skin tumors
  • Erythroderma (exfolliative dermatitis)
  • Lymphadenopathy

Ocular involvement may be evident in advanced cutaneous T-cell lymphoma. [2] Direct tumor infiltration may produce or contribute to corneal ulceration in such patients.

Cutaneous patches and plaques

The patch stage of mycosis fungoides is characterized by usually erythematous macules that may have a fine scale, may be single or multiple, and may be pruritic (see the image below). In dark-skinned individuals, the patches may appear as hypopigmented or hyperpigmented areas. As the patches become infiltrative, they evolve into palpable plaques.

Patch-stage mycosis fungoides. Patch-stage mycosis fungoides.

The plaques tend to be raised, demonstrating fine-scale, well-demarcated, erythematous shapes with irregular borders. Annular or serpiginous patterns with central clearing and pruritus are common. (See the images below.)

Plaque-stage mycosis fungoides. Plaque-stage mycosis fungoides.
Partially confluent, erythematous plaques in advan Partially confluent, erythematous plaques in advancing mycosis fungoides.
Close-up view of advancing plaque-stage mycosis fu Close-up view of advancing plaque-stage mycosis fungoides with partially confluent, erythematous plaques.

Patches and plaques may affect any area of the skin, but they are often distributed asymmetrically in the sun-protected areas that a bathing suit would cover (ie, hips, buttocks, groin, lower trunk, axillae, breasts). When mycosis fungoides affects the scalp, it is often accompanied by alopecia.

Skin tumors

Patients with evidence or a history of patchy or plaquelike skin lesions can also have tumors, which are red-violet nodules that may be dome-shaped, exophytic, or ulcerated. However, if only tumors are present, without preceding or concurrent patches or plaques, a diagnosis of mycosis fungoides is highly unlikely and another type of cutaneous T-cell lymphoma should be considered. [30, 1] (See the images below.)

Tumor-stage cutaneous T-cell lymphoma. Tumor-stage cutaneous T-cell lymphoma.
Tumor-stage mycosis fungoides. Tumor-stage mycosis fungoides.

Skin erythroderma

Sézary syndrome is characterized by erythroderma, which is often associated with marked pruritus and exfoliation, edema, and lichenification. Lymphadenopathy, onychodystrophy, and palmoplantar hyperkeratosis are also commonly associated. In addition, patients experience thickening of the facial skin folds (leonine facies) and ectropion of the eyelids. Sun exposure may be painful, as well as pruritic. (See the image below.)

Erythroderma of Sézary syndrome. Erythroderma of Sézary syndrome.

A few patients with Sézary syndrome have patchy, total-scalp, or universal alopecia. Follicular mycosis fungoides may present with alopecia; total-body hair loss may be evident in some patients with generalized erythroderma and Sézary syndrome. [65] The alopecia may also appear clinically identical to alopecia areata. However, skin biopsy specimens may reveal atypical T lymphocytes within the follicular epithelium or epidermis, sometimes with follicular mucinosis.

Lymphadenopathy

Extracutaneous involvement in mycosis fungoides becomes more clinically evident as the stages and extent of the disease progress. Peripheral lymphadenopathy is the most frequent site of extracutaneous involvement in mycosis fungoides.

Evaluate palpable lymphadenopathy by obtaining a biopsy, because the result influences the patient's stage, prognosis, and treatment.

Other signs of cutaneous T-cell lymphoma

Granulomatous slack skin syndrome shows circumscribed areas of pendulous, lax skin with a predilection for the axillae and groin. An association with Hodgkin lymphoma or with classic mycosis fungoides may be apparent. [66] Most patients have an indolent clinical course.

Acute adult T-cell leukemia/lymphoma is characterized by the presence of leukemia, lymphadenopathy, organomegaly, hypercalcemia, and, in approximately 50% of cases, skin lesions. Skin lesions most commonly include nodules or tumors (33%), generalized papules (22%), or plaques (19%). [42] Chronic and smoldering variants frequently manifest as skin lesions that closely resemble mycosis fungoides, whereas circulating neoplastic T cells are few or absent.

Subcutaneous panniculitis-like T-cell lymphoma is a rare form of cutaneous T-cell lymphoma. Patients are usually first seen with solitary or multiple nodules and plaques; these mainly involve the legs, although they may be more generalized. Ulceration is uncommon, but systemic symptoms such as fever, fatigue, and weight loss may be present. A hemophagocytic syndrome may be present and is generally associated with a rapidly progressive course. [67] Dissemination to extracutaneous sites is unusual. Subcutaneous panniculitis-like T-cell lymphoma may be preceded for years or decades by a seemingly benign panniculitis suggestive of chronic erythema nodosum. Rarely, it may produce scalp alopecia. [68]

Primary cutaneous peripheral T-cell lymphomas, unspecified, are a heterogeneous group of diseases for which the common characteristic is a lack of typical features of mycosis fungoides. Cutaneous gamma/delta-positive T-cell lymphoma, [31] which belongs to this group, [1, 32] usually has an aggressive course and manifests with disseminated plaques and/or ulceronecrotic nodules or tumors, particularly on the extremities. [57]

Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma, a provisional entity, is characterized by localized or disseminated eruptive papules, nodules, and tumors that show central ulceration and necrosis or superficial, hyperkeratotic patches and plaques. [38, 69]

Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma tends to be first apparent as a solitary plaque or tumor, generally on the face, neck, or upper trunk, although it may less commonly appear as 1 or several papules, nodules, or tumors. [70, 53]

Nasal-type extranodal NK/T-cell lymphoma usually appears as a destructive midfacial tumor or as multiple plaques or tumors, often with ulceration, preferentially on the trunk and extremities. Systemic symptoms such as fever, malaise, and weight loss may be present, and some cases are accompanied by a hemophagocytic syndrome.

Nasal-type extranodal NK/T-cell lymphoma has a variant that clinically resembles hydroa vacciniforme in which children, mainly in Latin America and Asia, have a papulovesicular eruption that typically occurs on sun-exposed areas, such as the face and upper extremities. [71, 72]

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