eMedicine Specialties > Dermatology > Lymphoma and Related Processes

Cutaneous T-Cell Lymphoma: Differential Diagnoses & Workup

Author: Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Coauthor(s): W Clark Lambert, MD, PhD, Professor and Head, Dermatopathology, Departments of Pathology and Dermatology, UMDNJ-New Jersey Medical School
Contributor Information and Disclosures

Updated: Nov 10, 2009

Differential Diagnoses

Atopic Dermatitis
Pemphigus Foliaceus
Contact Dermatitis, Allergic
Psoriasis, Plaque
Contact Dermatitis, Irritant
Psoriasis, Pustular
Lichen Planus
Tinea Corporis
Parapsoriasis

Other Problems to Be Considered

Erythroderma, nonlymphomatous
Erythema neurolyticum migrans

At times, disseminated infections such as leishmaniasis, leprosy, South American blastomycosis, coccidioidomycosis, and other deep fungal infections may mimic and require distinction from CTCL. Acne vulgaris, epidermal inclusion cysts, and insect bites may resemble FMF.

Workup

Laboratory Studies

  • For cutaneous T-cell lymphomas (CTCLs) or mycosis fungoides (MF), clinical features, the history of the disease, and histomorphology and cytomorphology findings yield clues that lead to a diagnosis in most cases. However, demonstration of a dominant T-cell clone in skin biopsy specimens by a molecular assay (ie, Southern blot, polymerase chain reaction) constitutes an additional diagnostic criterion to distinguish CTCLs from inflammatory dermatoses.
  • The diagnosis of SS should include one or more of the following7 :
    • An absolute Sézary cell count of least 1000 cells/µL
    • Demonstration of immunophenotypical abnormalities (an expanded CD4+ T-cell population resulting in a CD4/CD8 ratio of more than 10; loss of any or all of the T-cell antigens CD2, CD3, CD4, CD5; or loss of both CD4 and CD5)
    • Demonstration of a T-cell clone in the peripheral blood by molecular or cytogenetic methods: Flow cytometry may be useful for differential diagnosis of precursor and peripheral T-cell and NK-cell lymphomas.28
  • Following a diagnostic algorithm for the evaluation and diagnosis of erythroderma due to CTCL versus "reactive" causes of erythroderma may be helpful.29
  • See Histologic Findings.1

Other Tests

  • Neoplastic MF cells have a mature CD3+, CD4+, CD45RO+, CD8- memory T-cell phenotype. Rarely, otherwise-classic MF may have a CD4-, CD8+ mature T-cell phenotype.30 An aberrant phenotype, such as loss of pan–T cell antigens (eg, CD2, CD3, CD5), is not unusual.
  • An identical phenotype is seen in GSS syndrome and SS. Clonal T-cell receptor gene rearrangements are detected in most MF cases.31 Many structural and numerical chromosomal abnormalities have been described in the advanced stages of MF, but recurrent, MF-specific chromosomal translocations have not been identified. Chromosomal loss at 10q and abnormalities in P15, P16, and TP53 tumor suppressor genes are often evident with MF.
  • The neoplastic T cells in pagetoid reticulosis may have either a CD3+, CD4+, CD8- phenotype or a CD3+, CD4-, CD8+ phenotype, with CD30 often being expressed.32
  • Genetic features show T-cell receptor genes to be clonally rearranged in persons with MF, GSS syndrome, or SS. Demonstration of clonal T cells in the peripheral blood is an important diagnostic criterion that allows differentiation between SS and benign forms of erythroderma.7 Recurrent chromosomal translocations are not detected in persons with SS, but complex karyotypes are common, as is a consistent pattern of identical chromosomal abnormalities in SS as seen in MF.33
  • The neoplastic T cells in ATLL express a CD3+, CD4+, CD8- phenotype, with CD25 being highly expressed.8 T-cell receptor genes (TCR) are clonally rearranged; clonally integrated HTLV-1 genes are present and are useful in differentiating between chronic or smoldering variants of ATLL and classic MF or SS.
  • Panniculitislike T-cell lymphoma shows an alpha/beta+, CD3+, CD4-, CD8+ T-cell phenotype, with expression of cytotoxic proteins.11 CD30 and CD56 are not expressed. Neoplastic T cells do show clonal TCR gene rearrangements, although neither specific genetic abnormalities nor EBV has been identified.
  • Extranodal NK/T-cell lymphoma, nasal type, has neoplastic cells that express CD2, CD56, and cytoplasmic CD3.

Histologic Findings

In the early stages of MF, the histopathology is nonspecific,34,35,36,37  and the condition is often misdiagnosed as an inflammatory disorder. Early-patch MF shows superficial bandlike or lichenoid infiltrates, mainly consisting of lymphocytes and histiocytes. A few atypical cells with small-to-medium, highly indented (cerebriform), and sometimes hyperchromatic nuclei are present and are mostly confined to the epidermis (epidermotropism). They tend to colonize the basal layer of the epidermis either as single, often-haloed cells or in a linear configuration,31  especially at the tips of the rete ridges.

In MF plaques, the histologic changes are diagnostic; epidermotropism is generally more pronounced than in MF patches. The presence of intraepidermal collections of atypical cells (Pautrier microabscesses) is a highly characteristic feature observed in only a minority of cases (10%). In the tumor stage, the dermal infiltrates become more diffuse and epidermotropism may be lost. The tumor cells increase in number and size, demonstrating variable proportions of small, medium, and large cerebriform blast cells with prominent nuclei and intermediate forms. Transformation to a diffuse large cell lymphoma of either CD30- or CD30+ phenotype may occur, portending a poor prognosis. Eosinophils, plasma cells, and histiocytes are frequent companions.

Folliculocentric MF shows a primarily perivascular and periadnexal localization of the dermal infiltrate with variable involvement of the follicular epithelium by small, medium, or sometimes large hyperchromatic cells with cerebriform nuclei and sparing of the epidermis (folliculotropism instead of epidermotropism).1 Most have mucinous degeneration of the follicular epithelium (follicular mucinosis), best demonstrated with Alcian blue staining, and an admixture of eosinophils and sometimes plasma cells. Prominent infiltration of both follicular epithelium and eccrine sweat glands is often observed. Similar cases with prominent infiltration of eccrine sweat glands, often seen with alopecia, have been called syringotropic MF.38 Basaloid folliculolymphoid hyperplasia is a distinctive finding in follicular MF.39

Granulomatous MF shows sarcoidal, granuloma annulare–like, or giant cell–rich reactions.

GSS syndrome shows a dermal infiltrate composed of atypical T cells with a dissemination of many multinucleated giant cells containing fragments of elastic fibers.

Pagetoid reticulosis (Woringer-Kolopp disease) shows a hyperplastic epidermis with marked pagetoid infiltration by atypical haloed lymphoid cells, singly or arranged in nests. The upper dermis has a mixed infiltrate of lymphocytes or histiocytes.

The histology of SS may be nonspecific, but it is often similar to MF, although the cellular infiltrates in SS are more often monotonous,40,41  and epidermotropism may sometimes be absent. Involved lymph nodes have a dense, monotonous infiltrate of Sézary cells with effacement of the normal lymph node architecture, whereas bone marrow infiltrates, when present, are often sparse and mainly interstitial.42

In ATLL, the cutaneous nodules show a superficial or more diffuse infiltration of medium-to-large T cells with pleomorphic or multilobated nuclei, often with marked epidermotropism. The histologic picture may be the same as is seen with MF. In the smoldering type of ATLL, dermal infiltrates may be sparse, with only slightly atypical cells.

In SPTL, subcutaneous infiltrates simulate a panniculitis and show small, medium, or sometimes large pleomorphic T cells with hyperchromatic nuclei and often many macrophages.12 The overlying epidermis and dermis are typically not involved.43 Rimming of individual fat cells by neoplastic T cells is a helpful, although not completely specific, diagnostic feature.11 Necrosis, karyorrhexis, and cytophagocytosis are common.

Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma, characterized by a proliferation of epidermotropic CD8+ cytotoxic T cells, has an acanthotic or atrophic epidermis, necrotic keratinocytes, ulceration, and variable spongiosis, sometimes with blister formation.5,24 Epidermotropism tends to be marked, ranging from a linear distribution to a pagetoid pattern throughout the epidermis.

CGD-TCL has 3 major histologic patterns of involvement that can be present in the skin: epidermotropic, dermal, and subcutaneous.12 More than 1 is often present in the same patient in different biopsy specimens or within a single biopsy specimen.23 The lymphoma cells are generally medium to large with coarsely clumped chromatin, with large blastic cells with vesicular nuclei and prominent nucleoli being infrequent and apoptosis and necrosis common, often with angioinvasion. The subcutaneous involvement may demonstrate rimming of fat cells.

Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma shows dense, diffuse, or nodular infiltrates within the dermis with a tendency to infiltrate the subcutis, and epidermotropism is often present focally. A predominance of small/medium-sized pleomorphic T cells may be seen, with a smaller proportion of large pleomorphic cells present.44

Extranodal NK/T-cell lymphoma, nasal type, has dense dermal and often subcutaneous infiltrates with prominent angiocentricity and angiodestruction, often accompanied by extensive necrosis.45,46

Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma has a beta-F1+, CD3+, CD8+, granzymes-B+, perforin+, TIA-1+, CD45RA+, CD45RO, CD2-, CD4-, CD5-, CD7+/- phenotype.17,24 It is usually associated with EBV seronegativity. The lymphoma cells show clonal TCR gene rearrangements, although specific genetic abnormalities have not been described.

CGD-TCL12 lymphoma cells are generally of beta-F1-, CD3+, CD2+, CD5-, CD7+/-, CD56+ phenotype with strong expression of cytotoxic proteins. Most lack both CD4 and CD8, although CD8 may be expressed in some cases.23,47 In frozen-section specimens, the lymphoma cells are strongly positive for TCR-delta. If only paraffin sections are available, the absence of beta-F1 may be used to infer a gamma/delta origin.48 The lymphoma cells show clonal rearrangement of the TCR -gamma gene, while TCR -beta may be rearranged or deleted, but it is not expressed. EBV test results are usually negative.23

Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, a CD3+, CD4+, CD8-, CD30- phenotypic lymphoma, sometimes has loss of pan–T-cell markers. Cytotoxic proteins are generally not expressed.17 The TCR genes are clonally rearranged.25

Primary cutaneous PTL, type unspecified, shows an aberrant CD4+ T-cell phenotype with variable loss of pan–T-cell antigens. CD30 staining is negative or restricted to a few scattered tumor cells. Rare cases may show coexpression of CD56. Expression of cytotoxic proteins is uncommon.17

Staging

The staging systems for CTCL have been primarily designed to describe cases of MF and SS, but they also apply to the other entities within the CTCLs. In MF and SS and in many of these other diseases, the stage of the disease largely determines the prognosis.

Clinical staging of CTCL is straightforward; if patches and/or plaques, but no erythroderma or involvement of lymph nodes or viscera is present, the disease is in stage IA.

If the cutaneous involvement is less than 10% of the total body surface, the stage is IA. It is stage IB if 10% or more of the body surface is involved. If enlarged lymph nodes, histologically uninvolved with lymphoma, are also present, the disease is in stage IIA regardless of the extent of cutaneous involvement.

If skin tumors of lymphoma are present but no histologically proven internal involvement or erythroderma is present, the disease is in stage IIB, regardless of whether lymphadenopathy, patches, and/or plaques are also present. If erythroderma (ie, whole-body erythema) is present but histologically proven involvement of lymph nodes or viscera is not, the disease is in stage III, regardless of whether lymphadenopathy is noted.

If lymph nodes are involved with histologically proven lymphoma, the disease is in stage IVA. If viscera are involved with histologically proven lymphoma, it is in stage IVB.

These definitions are denoted in Table 1. Table 2 lists the TNMB (tumor, node, metastasis, blood) stage definitions. Table 3 is a comparison of the 2 systems.

Table 1. Staging of CTCL

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Table
StageSkin LesionsLymphadenopathyErythrodermaHistological Lymphoma
Patches
<10%		Plaques
³ 10%		TumorsLymph NodesViscera
IA+------
IB+ or -
+-----
IIA+ or -
+ or -+ or -+---
IIB+ or -+ or -++ or ----
III+ or -
+ or -+ or -+ or -+--
IVA+ or -
+ or -+ or -+ or -+ or -+-
IVB+ or -
+ or -+ or -+ or -+ or -+ or -+
StageSkin LesionsLymphadenopathyErythrodermaHistological Lymphoma
Patches
<10%		Plaques
³ 10%		TumorsLymph NodesViscera
IA+------
IB+ or -
+-----
IIA+ or -
+ or -+ or -+---
IIB+ or -+ or -++ or ----
III+ or -
+ or -+ or -+ or -+--
IVA+ or -
+ or -+ or -+ or -+ or -+-
IVB+ or -
+ or -+ or -+ or -+ or -+ or -+

Table 2. TNMB Staging of CTCL

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Table
Stage ClassStageDefinition
T
(Tumor)		T1 Patches/plaques involving <10% of body surface
T2 Patches/plaques involving ³ 10% of body surface
T3 Tumor(s) present on skin
T4 Erythroderma
N
(Nodes)		N0 No enlarged lymph node present
N1 Enlarged lymph nodes, histologically uninvolved
N2 No enlarged lymph node; one or more nodes histologically involved*
N3 Enlarged lymph nodes, histologically involved
M
(Metastasis to viscera)		M0 No visceral lesion present
M1 Visceral involvement
B
(Blood involvement)		B0 Circulating atypical lymphocytes (Sézary cells) £ 5% of lymphocytes
B1 Circulating atypical lymphocytes ³ 5% of lymphocytes (Sézary syndrome)
Stage ClassStageDefinition
T
(Tumor)		T1 Patches/plaques involving <10% of body surface
T2 Patches/plaques involving ³ 10% of body surface
T3 Tumor(s) present on skin
T4 Erythroderma
N
(Nodes)		N0 No enlarged lymph node present
N1 Enlarged lymph nodes, histologically uninvolved
N2 No enlarged lymph node; one or more nodes histologically involved*
N3 Enlarged lymph nodes, histologically involved
M
(Metastasis to viscera)		M0 No visceral lesion present
M1 Visceral involvement
B
(Blood involvement)		B0 Circulating atypical lymphocytes (Sézary cells) £ 5% of lymphocytes
B1 Circulating atypical lymphocytes ³ 5% of lymphocytes (Sézary syndrome)
*Uncommon finding, usually not considered/investigated.
 
Table 3. Comparison of Staging Systems for CTCL

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Table
Clinical StageTNM (B) Stage
IAT1 N0 M0
IIBT2 N0 M0
IIAT1 N1 M0 T2 N1 M0  
IIBT3 N0 M0 T3 N1 M0   
IIIT4 N0 M0 T4 N1 M0   
IVAT1 N2 M0 T2 N2 M0 T3 N2 M0 T4 N2 M0
T1 N3 M0 T2 N3 M0 T3 N3 M0 T4 N3 M0
IVBT1 N0 M1 T2 N0 M1 T3 N0 M1 T4 N0 M1
T1 N1 M1 T2 N1 M1 T3 N1 M1 T4 N1 M1
T1 N2 M1 T2 N2 M1 T3 N2 M1 T4 N2 M1
T1 N3 M1 T2 N3 M1 T3 N3 M1 T4 N3 M1
Clinical StageTNM (B) Stage
IAT1 N0 M0
IIBT2 N0 M0
IIAT1 N1 M0 T2 N1 M0  
IIBT3 N0 M0 T3 N1 M0   
IIIT4 N0 M0 T4 N1 M0   
IVAT1 N2 M0 T2 N2 M0 T3 N2 M0 T4 N2 M0
T1 N3 M0 T2 N3 M0 T3 N3 M0 T4 N3 M0
IVBT1 N0 M1 T2 N0 M1 T3 N0 M1 T4 N0 M1
T1 N1 M1 T2 N1 M1 T3 N1 M1 T4 N1 M1
T1 N2 M1 T2 N2 M1 T3 N2 M1 T4 N2 M1
T1 N3 M1 T2 N3 M1 T3 N3 M1 T4 N3 M1


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References
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References

  1. Burg G, Kempf W. Etiology and pathogenesis of cutaneous lymphomas. In: Burg G, Kempf W. Cutaneous Lymphomas. London: Taylor & Francis; 2005.

  2. Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. May 15 2005;105(10):3768-85. [Medline].

  3. Burg G, Kempf W, Cozzio A, Dobbeling U, Feit J, Golling P, et al. Cutaneous malignant lymphomas: update 2006. J Dtsch Dermatol Ges. Nov 2006;4(11):914-33. [Medline].

  4. Khamaysi Z, Ben-Arieh Y, Izhak OB, Epelbaum R, Dann EJ, Bergman R. The Applicability of the New WHO-EORTC Classification of Primary Cutaneous Lymphomas to a Single Referral Center. Am J Dermatopathol. Feb 2008;30(1):37-44. [Medline].

  5. Berti E, Tomasini D, Vermeer MH, Meijer CJ, Alessi E, Willemze R. Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas. A distinct clinicopathological entity with an aggressive clinical behavior. Am J Pathol. Aug 1999;155(2):483-92. [Medline].

  6. Kempf W, Ostheeren-Michaelis S, Paulli M, Lucioni M, Wechsler J, Audring H, et al. Granulomatous mycosis fungoides and granulomatous slack skin: a multicenter study of the Cutaneous Lymphoma Histopathology Task Force Group of the European Organization For Research and Treatment of Cancer (EORTC). Arch Dermatol. Dec 2008;144(12):1609-17. [Medline].

  7. Vonderheid EC, Bernengo MG, Burg G, Duvic M, Heald P, Laroche L, et al. Update on erythrodermic cutaneous T-cell lymphoma: report of the International Society for Cutaneous Lymphomas. J Am Acad Dermatol. Jan 2002;46(1):95-106. [Medline].

  8. Setoyama M, Katahira Y, Kanzaki T. Clinicopathologic analysis of 124 cases of adult T-cell leukemia/lymphoma with cutaneous manifestations: the smouldering type with skin manifestations has a poorer prognosis than previously thought. J Dermatol. Dec 1999;26(12):785-90. [Medline].

  9. Weenig RH, Ng CS, Perniciaro C. Subcutaneous panniculitis-like T-cell lymphoma: an elusive case presenting as lipomembranous panniculitis and a review of 72 cases in the literature. Am J Dermatopathol. Jun 2001;23(3):206-15. [Medline].

  10. Hoque SR, Child FJ, Whittaker SJ, Ferreira S, Orchard G, Jenner K, et al. Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathological, immunophenotypic and molecular analysis of six patients. Br J Dermatol. Mar 2003;148(3):516-25. [Medline].

  11. Massone C, Chott A, Metze D, Kerl K, Citarella L, Vale E, et al. Subcutaneous, blastic natural killer (NK), NK/T-cell, and other cytotoxic lymphomas of the skin: a morphologic, immunophenotypic, and molecular study of 50 patients. Am J Surg Pathol. Jun 2004;28(6):719-35. [Medline].

  12. Burg G, Dummer R, Wilhelm M, Nestle F, Ott MM, Feller A, et al. A subcutaneous delta-positive T-cell lymphoma that produces interferon gamma. N Engl J Med. Oct 10 1991;325(15):1078-81. [Medline].

  13. El Shabrawi-Caelen L, Cerroni L, Kerl H. The clinicopathologic spectrum of cytotoxic lymphomas of the skin. Semin Cutan Med Surg. Jun 2000;19(2):118-23. [Medline].

  14. Miyamoto T, Yoshino T, Takehisa T, Hagari Y, Mihara M. Cutaneous presentation of nasal/nasal type T/NK cell lymphoma: clinicopathological findings of four cases. Br J Dermatol. Sep 1998;139(3):481-7. [Medline].

  15. Arnulf B, Copie-Bergman C, Delfau-Larue MH, Lavergne-Slove A, Bosq J, Wechsler J, et al. Nonhepatosplenic gammadelta T-cell lymphoma: a subset of cytotoxic lymphomas with mucosal or skin localization. Blood. Mar 1 1998;91(5):1723-31. [Medline].

  16. Jaffe ES, Krenacs L, Raffeld M. Classification of cytotoxic T-cell and natural killer cell lymphomas. Semin Hematol. Jul 2003;40(3):175-84. [Medline].

  17. Bekkenk MW, Vermeer MH, Jansen PM, van Marion AM, Canninga-van Dijk MR, Kluin PM, et al. Peripheral T-cell lymphomas unspecified presenting in the skin: analysis of prognostic factors in a group of 82 patients. Blood. Sep 15 2003;102(6):2213-9. [Medline].

  18. Roeschm A, Schleyer V, Landthaler M, Vogt T. Follicular mycosis fungoides: variability of a rare entity. Skinmed. Jan-Feb 2005;4(1):12-7. [Medline].

  19. Kohler S. Extranodal NK/T-cell lymphoma, nasal type. In: LeBoit P, Burg G, Weedon D, Lyon SA. WHO Books: Tumors of the Skin. Geneva: World Health Organization IARC. X. 2006:191-2.

  20. Clarijs M, Poot F, Laka A, Pirard C, Bourlond A. Granulomatous slack skin: treatment with extensive surgery and review of the literature. Dermatology. 2003;206(4):393-7. [Medline].

  21. Marzano AV, Berti E, Paulli M, Caputo R. Cytophagic histiocytic panniculitis and subcutaneous panniculitis-like T-cell lymphoma: report of 7 cases. Arch Dermatol. Jul 2000;136(7):889-96. [Medline].

  22. Torok L, Gurbity TP, Kirschner A, Krenacs L. Panniculitis-like T-cell lymphoma clinically manifested as alopecia. Br J Dermatol. Oct 2002;147(4):785-8. [Medline].

  23. Toro JR, Liewehr DJ, Pabby N, Sorbara L, Raffeld M, Steinberg SM, et al. Gamma-delta T-cell phenotype is associated with significantly decreased survival in cutaneous T-cell lymphoma. Blood. May 1 2003;101(9):3407-12. [Medline].

  24. Santucci M, Pimpinelli N, Massi D, Kadin ME, Meijer CJ, Muller-Hermelink HK, et al. Cytotoxic/natural killer cell cutaneous lymphomas. Report of EORTC Cutaneous Lymphoma Task Force Workshop. Cancer. Feb 1 2003;97(3):610-27. [Medline].

  25. von den Driesch P, Coors EA. Localized cutaneous small to medium-sized pleomorphic T-cell lymphoma: a report of 3 cases stable for years. J Am Acad Dermatol. Apr 2002;46(4):531-5. [Medline].

  26. Barrionuevo C, Anderson VM, Zevallos-Giampietri E, Zaharia M, Misad O, Bravo F, et al. Hydroa-like cutaneous T-cell lymphoma: a clinicopathologic and molecular genetic study of 16 pediatric cases from Peru. Appl Immunohistochem Mol Morphol. Mar 2002;10(1):7-14. [Medline].

  27. Chen HH, Hsiao CH, Chiu HC. Hydroa vacciniforme-like primary cutaneous CD8-positive T-cell lymphoma. Br J Dermatol. Sep 2002;147(3):587-91. [Medline].

  28. Karube K, Aoki R, Nomura Y, Yamamoto K, Shimizu K, Yoshida S, et al. Usefulness of flow cytometry for differential diagnosis of precursor and peripheral T-cell and NK-cell lymphomas: Analysis of 490 cases. Pathol Int. Feb 2008;58(2):89-97. [Medline].

  29. Russell-Jones R. Diagnosing erythrodermic cutaneous T-cell lymphoma. Br J Dermatol. Jul 2005;153(1):1-5. [Medline].

  30. Petrella T, Comeau MR, Maynadie M, Couillault G, De Muret A, Maliszewski CR, et al. 'Agranular CD4+ CD56+ hematodermic neoplasm' (blastic NK-cell lymphoma) originates from a population of CD56+ precursor cells related to plasmacytoid monocytes. Am J Surg Pathol. Jul 2002;26(7):852-62. [Medline].

  31. Smoller BR, Santucci M, Wood GS, Whittaker SJ. Histopathology and genetics of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. Dec 2003;17(6):1277-311. [Medline].

  32. Haghighi B, Smoller BR, LeBoit PE, Warnke RA, Sander CA, Kohler S. Pagetoid reticulosis (Woringer-Kolopp disease): an immunophenotypic, molecular, and clinicopathologic study. Mod Pathol. May 2000;13(5):502-10. [Medline].

  33. Mao X, Lillington D, Scarisbrick JJ, Mitchell T, Czepulkowski B, Russell-Jones R, et al. Molecular cytogenetic analysis of cutaneous T-cell lymphomas: identification of common genetic alterations in Sézary syndrome and mycosis fungoides. Br J Dermatol. Sep 2002;147(3):464-75. [Medline].

  34. Burg G, Zwingers T, Staegemeir E, Santucci M. Interrater and intrarater variabilities in the evaluation of cutaneous lymphoproliferative T-cell infiltrates. EORTC-Cutaneous Lymphoma Project Group. Dermatol Clin. Apr 1994;12(2):311-4. [Medline].

  35. Santucci M, Biggeri A, Feller AC, Massi D, Burg G. Efficacy of histologic criteria for diagnosing early mycosis fungoides: an EORTC cutaneous lymphoma study group investigation. European Organization for Research and Treatment of Cancer. Am J Surg Pathol. Jan 2000;24(1):40-50. [Medline].

  36. Santucci M, Smoller B. ISCL study on early diagnosis of mycosis fungoides. (in preparation).

  37. Pimpinelli N, Olsen EA, Santucci M, Vonderheid E, Haeffner AC, Stevens S, et al. Defining early mycosis fungoides. J Am Acad Dermatol. Dec 2005;53(6):1053-63. [Medline].

  38. Zelger B, Sepp N, Weyrer K, Grunewald K, Zelger B. Syringotropic cutaneous T-cell lymphoma: a variant of mycosis fungoides?. Br J Dermatol. Jun 1994;130(6):765-9. [Medline].

  39. Gerami P, Guitart J. Basaloid folliculolymphoid hyperplasia: a distinctive finding in follicular mycosis fungoides. J Cutan Pathol. Dec 2007;34 Suppl 1:29-32. [Medline].

  40. Imai S, Burg G, Braun-Falco O. Mycosis fungoides and Sezary's syndrome show distinct histomorphological features. Dermatologica. 1986;173(3):131-5. [Medline].

  41. Kamarashev J, Burg G, Kempf W, Hess Schmid M, Dummer R. Comparative analysis of histological and immunohistological features in mycosis fungoides and Sézary syndrome. J Cutan Pathol. Sep 1998;25(8):407-12. [Medline].

  42. Sibaud V, Beylot-Barry M, Thiebaut R, Parrens M, Vergier B, Delaunay M, et al. Bone marrow histopathologic and molecular staging in epidermotropic T-cell lymphomas. Am J Clin Pathol. Mar 2003;119(3):414-23. [Medline].

  43. Takeshita M, Okamura S, Oshiro Y, Imayama S, Okamoto S, Matsuki Y, et al. Clinicopathologic differences between 22 cases of CD56-negative and CD56-positive subcutaneous panniculitis-like lymphoma in Japan. Hum Pathol. Feb 2004;35(2):231-9. [Medline].

  44. Beljaards RC, Meijer CJ, Van der Putte SC, Hollema H, Geerts ML, Bezemer PD, et al. Primary cutaneous T-cell lymphoma: clinicopathological features and prognostic parameters of 35 cases other than mycosis fungoides and CD30-positive large cell lymphoma. J Pathol. Jan 1994;172(1):53-60. [Medline].

  45. Chan JK, Sin VC, Wong KF, Ng CS, Tsang WY, Chan CH, et al. Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm. Blood. Jun 15 1997;89(12):4501-13. [Medline].

  46. Natkunam Y, Smoller BR, Zehnder JL, Dorfman RF, Warnke RA. Aggressive cutaneous NK and NK-like T-cell lymphomas: clinicopathologic, immunohistochemical, and molecular analyses of 12 cases. Am J Surg Pathol. May 1999;23(5):571-81. [Medline].

  47. de Wolf-Peeters C, Achten R. gammadelta T-cell lymphomas: a homogeneous entity?. Histopathology. Apr 2000;36(4):294-305. [Medline].

  48. Jones D, Vega F, Sarris AH, Medeiros LJ. CD4-CD8-"Double-negative" cutaneous T-cell lymphomas share common histologic features and an aggressive clinical course. Am J Surg Pathol. Feb 2002;26(2):225-31. [Medline].

  49. Knobler E. Current management strategies for cutaneous T-cell lymphoma. Clin Dermatol. May-Jun 2004;22(3):197-208. [Medline].

  50. Ysebaert L, Truc G, Dalac S, Lambert D, Petrella T, Barillot I, et al. Ultimate results of radiation therapy for T1-T2 mycosis fungoides (including reirradiation). Int J Radiat Oncol Biol Phys. Mar 15 2004;58(4):1128-34. [Medline].

  51. Onozuka T, Yokota K, Kawashima T, Shimada H, Kodama K, Kobayashi H, et al. An elderly patient with mycosis fungoides successfully treated with chronic low-dose oral etoposide therapy. Clin Exp Dermatol. Jan 2004;29(1):91-2. [Medline].

  52. Dummer R, Urosevic M, Kempf W, Kazakov D, Burg G. Imiquimod induces complete clearance of a PUVA-resistant plaque in mycosis fungoides. Dermatology. 2003;207(1):116-8. [Medline].

  53. Apisarnthanarax N, Talpur R, Ward S, Ni X, Kim HW, Duvic M. Tazarotene 0.1% gel for refractory mycosis fungoides lesions: an open-label pilot study. J Am Acad Dermatol. Apr 2004;50(4):600-7. [Medline].

  54. Singh F, Lebwohl MG. Cutaneous T-cell lymphoma treatment using bexarotene and PUVA: a case series. J Am Acad Dermatol. Oct 2004;51(4):570-3. [Medline].

  55. Jones GW, Hoppe RT, Glatstein E. Electron beam treatment for cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. Oct 1995;9(5):1057-76. [Medline].

  56. Leverkus M, Rose C, Brocker EB, Goebeler M. Follicular cutaneous T-cell lymphoma: beneficial effect of isotretinoin for persisting cysts and comedones. Br J Dermatol. Jan 2005;152(1):193-4. [Medline].

  57. Jacob R, Scala M, Fung MA. A case of syringotropic cutaneous T-cell lymphoma treated with local radiotherapy. J Am Acad Dermatol. Jan 2009;60(1):152-4. [Medline].

  58. Russell-Jones R. Extracorporeal photopheresis in cutaneous T-cell lymphoma. Inconsistent data underline the need for randomized studies. Br J Dermatol. Jan 2000;142(1):16-21. [Medline].

  59. Lundin J, Hagberg H, Repp R, Cavallin-Stahl E, Freden S, Juliusson G, et al. Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome. Blood. Jun 1 2003;101(11):4267-72. [Medline].

  60. Fukushima T, Horio K, Matsuo E, Imanishi D, Yamasaki R, Tsushima H, et al. Successful cord blood transplantation for mycosis fungoides. Int J Hematol. Dec 2008;88(5):596-8. [Medline].

  61. Lambert WC, Cohen PJ, Schwartz RA. Surgical management of mycosis fungoides. J Med. 1997;28(3-4):211-22. [Medline].

  62. Foss F. Overview of cutaneous T-cell lymphoma: prognostic factors and novel therapeutic approaches. Leuk Lymphoma. 2003;44 Suppl 3:S55-61. [Medline].

  63. Kaye FJ, Bunn PA Jr, Steinberg SM, Stocker JL, Ihde DC, Fischmann AB, et al. A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides. N Engl J Med. Dec 28 1989;321(26):1784-90. [Medline].

  64. Tancrede-Bohin E, Ionescu MA, de La Salmoniere P, Dupuy A, Rivet J, Rybojad M, et al. Prognostic value of blood eosinophilia in primary cutaneous T-cell lymphomas. Arch Dermatol. Sep 2004;140(9):1057-61. [Medline].

  65. van Doorn R, Scheffer E, Willemze R. Follicular mycosis fungoides, a distinct disease entity with or without associated follicular mucinosis: a clinicopathologic and follow-up study of 51 patients. Arch Dermatol. Feb 2002;138(2):191-8. [Medline].

  66. Scarisbrick JJ, Whittaker S, Evans AV, Fraser-Andrews EA, Child FJ, Dean A, et al. Prognostic significance of tumor burden in the blood of patients with erythrodermic primary cutaneous T-cell lymphoma. Blood. Feb 1 2001;97(3):624-30. [Medline].

  67. Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). Br J Haematol. Nov 1991;79(3):428-37. [Medline].

  68. Fink-Puches R, Zenahlik P, Back B, Smolle J, Kerl H, Cerroni L. Primary cutaneous lymphomas: applicability of current classification schemes (European Organization for Research and Treatment of Cancer, World Health Organization) based on clinicopathologic features observed in a large group of patients. Blood. Feb 1 2002;99(3):800-5. [Medline].

  69. Bekkenk MW, Jansen PM, Meijer CJ, Willemze R. CD56+ hematological neoplasms presenting in the skin: a retrospective analysis of 23 new cases and 130 cases from the literature. Ann Oncol. Jul 2004;15(7):1097-108. [Medline].

  70. Mraz-Gernhard S, Natkunam Y, Hoppe RT, LeBoit P, Kohler S, Kim YH. Natural killer/natural killer-like T-cell lymphoma, CD56+, presenting in the skin: an increasingly recognized entity with an aggressive course. J Clin Oncol. Apr 15 2001;19(8):2179-88. [Medline].

  71. Burg G, Kempf W. Therapy of cutaneous lymphomas. In: Burg G, Kempf W. Cutaneous Lymphomas. London: Taylor & Francis; 2005:475-528.

  72. Burg G, Kempf W, Cozzio A, Feit J, Willemze R, S Jaffe E, et al. WHO/EORTC classification of cutaneous lymphomas 2005: histological and molecular aspects. J Cutan Pathol. Nov 2005;32(10):647-74. [Medline].

  73. Santucci M, Biggeri A, Feller AC, et al. Efficacy of histologic criteria for diagnosing early mycosis fungoides: an EORTC cutaneous lymphoma study group investigation. European Organization for Research and Treatment of Cancer. Am J Surg Pathol. Jan 2000;24(1):40-50. [Medline].

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Further Reading

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Keywords

CTCL, mycosis fungoides, patch stage mycosis fungoides, large plaque parapsoriasis, plaque stage mycosis fungoides, tumor stage mycosis fungoides, d'emblee mycosis fungoides, primary cutaneous pleomorphic mycosis fungoides, medium-sized T-cell lymphoma, large cell CD30+ T-cell lymphoma, large cell CD30- T-cell lymphomas, solitary mycosis fungoides, unilesional mycosis fungoides, unilesional pagetoid reticulosis, Woringer-Kolopp disease, follicular mycosis fungoides, Sézary syndrome, Sezary syndrome, Sezary's syndrome, erythrodermic mycosis fungoides, granulomatous slack skin, granulomatous CTCL, granulomatous mycosis fungoides, angiocentric CTCL, subcutaneous CTCL, panniculitis-like CTCL, panniculitislike CTCL, lipotropic CTCL, panniculotropic CTCL, subcutaneous mycosis fungoides, suppressor T-cell CTCL, CD8+ CTCL, delta/gamma CTCL, NK cell CTCL, natural killer CTCL, KI-1+ large cell CTCL

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Contributor Information and Disclosures

Author

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

W Clark Lambert, MD, PhD, Professor and Head, Dermatopathology, Departments of Pathology and Dermatology, UMDNJ-New Jersey Medical School
W Clark Lambert, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, American Dermatological Association, American Society of Dermatopathology, International Academy of Pathology, Medical Society of New Jersey, Sigma Xi, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Günter Burg, MD, Professor and Chairman Emeritus, Department of Dermatology, University of Zürich School of Medicine; Delegate of The Foundation for Modern Teaching and Learning in Medicine Faculty of Medicine, University of Zürich, Switzerland
Günter Burg, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, International Society for Dermatologic Surgery, North American Clinical Dermatologic Society, and Pacific Dermatologic Association
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey Meffert, MD, Assistant Clinical Professor of Dermatology, University of Texas Health Science Center-San Antonio
Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, and Texas Dermatological Society
Disclosure: Nothing to disclose.

CME Editor

Catherine M Quirk, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania
Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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