Cutaneous T-cell lymphoproliferative disorders (CTCLs)

Classification of primary cutaneous T-cell lymphoproliferative disorders:

The malignant lymphomas are classified according to the EORTC : European Organization for Research and Treatment of Cancer classification

• Benign lymphoproliferative CTCL

  • cutaneous lymphoid hyperplasia

  • lymphomatoid drug eruptions

  • lymphomatoid contact dermatitis

  • actinic reticuloid

  • pseudolymphomatous angiokeratoma

  • small plaque parapsoriasis

• Indolent malignant disorders

  • mycosis fungoides

    • large plaque parapsoriasis

    • mycosis fungoides-associated follicular mucinosis

    • Pagetoid reticulosis

  • CD30-positive lymphoproliferative disorders

    • primary cutaneous CD30-positive large cell lymphoma

      • anaplastic

      • immunoblastic

      • pleomorphic

    • lymphomatoid papulosis

    • borderline cases

• Aggressive malignant CTCLs

  • Sezary syndrome

  • Large cell, CD30-negative CTCLs

    • immunoblastic

    • pleomorphic

• provisional

  • granulomatous slack skin

  • pleomorphic small/medium size CTCLs

  • subcutaneous panniculitis-like T-cell lymphoma

• not included in EORTC classification

  • gd cutaneous lymphoma

  • primary cutaneous CD8-positive epidermotropic cytotoxic T-cell lymphoma

  • hydroa vacciniforme-like lymphoma

Benign lymphoproliferative CTCLs can be differentiated from lymphomas by:

• clinicopathological correlation

• lack of an aberrant immunophenotype : 0/11 cases, no loss of CD2, CD3 or CD5 ¹. Rare cases of psoriasis have shown an aberrant immunophenotype. Mycosis fungoides shows an aberrant immunophenotype in the majority of cases.

• lack of clonal T cell receptor gene rearrangements. Rare cases of contact dermatitis have shown clonal TCR gene rearrangements.

cutaneous lymphoid hyperplasia

lymphomatoid drug eruptions Causative drugs include anticonvulsants (phenytoin, hydantoin, carbamazepine), cardiac drugs (atenolol, ACE inhibitors, mexiletine) , antihistamines, cyclosporine and allopurinol. Patients may present with a solitary plaque, multiple plaques or erythroderma. There is a lichenoid or nodular lymphohistiocytic dermal infiltrate. There may be atypia of lymphocytes but epidermotropism, Pautrier microabscesses and mitoses are lacking. The features indicating a benign infiltrate are:

• paucity of lesions
  

• no predilection for sun-shielded sites
  

• absence of a classical arcuate infiltrated plaque morphology
  

• resolution on cessation of the medication

The differential diagnosis includes adult adult T-cell leukaemia/lymphoma; numerous histiocytes forming granulomata and eosinophils favour a benign diagnosis.

lymphomatoid contact dermatitis may be caused by rubber, chromate, nickel or chromate. The differential includes mycosis fungoides. Spongiosis and eosinophils favour a benign diagnosis.

actinic reticuloid (chronic actinic dermatitis): is a disease of the middle-aged, especially males. It is exquisitely photosensitive. Scaly eczematous plaques and papules occur over sun-exposed areas. There is acanthosis, spongiosis and a superficial dermal perivascular lymphocytic infiltrate. Severe cases show Pautrier-like microabscesses and epidermotropism, resembling mycosis fungoides . The presence of plasma cells and eosinophils favours a benign diagnosis.

acral pseudolymphomatous angiokeratoma of children shows papules of acral sites. There is a dense upper dermal infiltrate of T-cells with scattered plasma cells.

small plaque parapsoriasis (SPP, parapsoriasis small patch, parapsoriasis en plaques small plaque variety, erythrodermies pityriasiques en plaque disseminées, xanthoerythrodermia perstand, digitate dermatosis, chronic superficial scaly dermatitis). The patients are usually middle-aged. The scaly patches are less than 5 cm in diameter. The scales are delicate, cigarette-paper like. There is focal parakeratosis, acanthosis and sometimes a psoriasiform epidermis. There may be slight spongiosis and lymphocytic exocytosis. There is a mild superficial perivascular lymphocytic infiltrate. The lymphocytes do not show atypia.

Pagetoid reticulosis. The generalised from is probably variant of mycosis fungoides. The localised form should probably be classified separately.

Lymphomatoid papulosis: this usually behaves as a benign condition, although some cases progress to lymphoma (ALCL, Mycosis fungoides or Hodgkin lymphoma). Skin lesions are small (<2.5 cm) and regress within 3 to 6 weeks. They may resemble arthropod bites. Extracutaneous disease indicates that it has progressed to lymphoma. There is pseudoepitheliomatous hyperplasia with an underlying wedge-shaped infiltrate. The cutaneous infiltrates consist of atypical T-cells admixed with inflammatory cells (neutrophils, eosinophils, macrophages and small lymphocytes).

• Type A lesions contain many Reed-Sternberg-like CD30+ cells, along with many inflammatory cells.

• Type B lesions more closely resemble Mycosis fungoides, containing cells with small to medium size lymphoid cells with cerebriform nuclei, but few inflammatory cells. The infiltrate may be perivascular or band-like. The cells are CD3+, CD4+ but CD30-.

• Type C lesions (borderline lesions). Those showing the clinical behavior of regression but the histology of lymphoma. There are large atypical CD30+ T-cells arranged in clusters and sheets, resembling ALCL. However, they are restricted to the dermis and superficial subcutis.

• When clinically malignant but showing the histology of lymphomatoid papulosis, they are referred to as anaplastic lymphoma, lymphomatoid papulosis-like.

granulomatous slack skin is best regarded as a specific entity. There are slowly developing folds of atrophic skin in the axilla and groin which eventually become pendulous. It is a disease of white females with an age of onset varying from 10 to 50 years. There is a granulomatous infiltrate of atypical T-cell mixed with macrophages and multinucleate giant cells, the latter showing lymphophagocytosis. There is a loss of elastic fibres with elastophagocytosis by macrophages. A granulomatous vasculitis has also been documented. The giant cells are positive for CD68 and sometimes for S-100. There is an association with mycosis fungoides, which includes a granulomatous variant, Hodgkin lymphoma, non-Hodgkin lymphoma and Langerhans cell histiocytosis.

hydroa vacciniforme-like lymphoma² The is a cutaneous lymphoproliferative disorder of children seen in Asia and Central/South America. It is usually of NK-cell, rarely T--cell type. The lymphoid infiltrate is positive for EBV. There is a papulovesicular eruption on sun-exposed skin, with ulceration. Systemic symptoms may include fever, weight loss, lymphadenopathy and hepatosplenomegaly. There may be haemophagocytosis. Episodic eruptions may be precipitated by insect bites. The condition overlaps with NK/T cell lymphoma, nasal type. Prognosis is poor, with poor response to chemotherapy.

The lymphoid infiltrate extends from epidermis to subcutis, with necrosis, angiocentricity and angioinvasion. There is CD56 positivity.

The differential is benign hydroa vacciniforme of childhood, in which there is a vesicular eruption with scarring in response to ultraviolet light.

Differential diagnosis

• B-cell pseudolymphomas:

  • lymphocytoma cutis

  • Spiegler-Fendt sarcoid

  • lymphadenosis benigna cutis

  • cutaneous lymphoplasia

• B-cell lymphomas of skin

  • lymphomatoid granulomatosis

  • primary cutaneous follicular lymphoma

References

Liu, V. and McKee, P.H. Cutaneous T-cell lymphoproliferative disorders: approach for the surgical pathologist: recent advances and clarification of confused issues. Adv Anat Pathol 2002;9:79-100.

¹ Bakels, V., van Oostveen, J.W., van der Putte, S.C., Meijer, C.J. and Willemze, R. Immunophenotyping and gene rearrangement analysis provide additional criteria to differentiate between cutaneous T-cell lymphomas and pseudo- T-cell lymphomas. Am J Pathol 1997;150:1941-9.

² VE Nava and ES Jaffe. The pathology of NK-cell lymphomas and leukamias. Adv Anat Pathol 2005;12:27-34.

This page last revised 24.3.2005.

©SMUHT/PW Bishop