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Background

The understanding of skin lymphomas has followed the evolution of lymph node based lymphomas. There has been an explosive growth in the classification of these lymphomas with new insights gained from molecular biology, hematopathology, and immunohistochemistry. Ultimately, the utility of any classification system is to predict behavior of each cancer and help to direct therapy. The EORTC classification is one system that does a fine job of organizing the myriad of names of cutaneous lymphomas. Briefly, cutaneous lymphomas can be divided into T and B cell lineage, with T cell lymphomas the most common. Within these divisions, further distinctions based upon the clinical behavior can be gleaned.

It must be remembered that cutaneous lymphomas are relatively rare. Of these variants, mycosis fungoides is the most common and sometimes has been used indiscriminately to describe all cutaneous T cell lymphomas (CTCL). To further complicate matters, there are a few skin rashes which have been classified under CTCL which at best, have an unpredictable behavior with an increased risk of progression to lymphoma. These rashes called parapsoriasis have been broadly divided into small and large plaque parapsoriasis. The name derives from the clinical appearance of these scaly rashes which resemble psoriasis. These rashes were chronic conditions and relatively resistant to therapy. Within recent years, large plaque parapsoriasis (also known as atrophic parapsoriasis, retiform parapsoriasis, and poikilodermal atrophicans vasculare) has become synonymous with mycosis fungoides. Careful studies have found progression to CTCL in 10-30% of cases. The problem is identifying which cases will progress. The lesions usually start as large erythematous patch or plaque on the trunk or extremities, usually 10 cm. or more in diameter. Atrophy may follow and nearly all cases which have progressed to lymphoma have done so through this atrophic stage.

Finally, there are a number of skin diseases which have been broadly classified as pseudolymphomas. These entities mimic cutaneous lymphomas both clinically and histologically but are benign.

The pathogenesis or origin of cutaneous lymphomas is actively debated. One theory suggests an early precursor lesion with a persistent stimulation by an antigen, possibly a superantigen. This leads to epidermal derived growth factors which attract lymphocytes. Additional acquired defects in cell cycle regulation and apoptosis, early CTCL may develop. These neoplastic T-helper-2 cells proliferate because they cannot be blocked by endogenous interferon-gamma because of IFN-gamma resistance. There is a low proliferation rate at this point. With increasing genetic alterations, there is a reduced dependency on epidermal derived growth factors and subsequently a high proliferation rate.

In contrast, cutaneous B cell lymphomas (CBCL) have a different pathogenesis. Like CTCL, they are antigen driven processes. It appears that heavy chain genes (VH) of the B cells show significant mutations. Once this occurs, a neoplastic clone develops. There are definitely some environmental factors associated with this such as Borrelia burgdorferi infection (agent of Lyme disease). The term SALT (Skin Associated Lymphoid Tissue) has been applied to some of these B cell lymphomas, citing the similarity of CBCL with other B cell lymphomas arising within mucosa such as the salivary gland and gastrointestinal tract.

The similarities include:

Nonaggressive clinical behavior
Subtle histologic differences from true follicular center cells and intermediate cells of the lymph nodes
Tumor cells with unimodal morphometric features intermediate between centrocytes and centroblasts of nodal follicular center cells
Characteristic polymorphism of the neoplastic cellular infiltrate
Multiphasic histologic features with the various cell types often intermingled
Lymphoepithelial lesions
Frequent CD5- CD10- phenotype of neoplastic B cells
Nerve growth factor receptor+, CD14- CD21 +/- phenotype of associated dendritic cells
Lack of either t(11;14)/t(14;18) translocation or bcl-1/bcl-2 gene and c-myc oncogene rearrangements

OUTLINE

Epidemiology  
Disease Associations  
Pathogenesis  
Laboratory/Radiologic/Other Diagnostic Testing  
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Special Stains/
Immunohistochemistry/
Electron Microscopy
 
Commonly Used Terms  
Internet Links  

EPIDEMIOLOGY CHARACTERIZATION
SYNONYMS Cutaneous Lymphoma
INCIDENCE In a recent survey of cutaneous lymphomas occurring in 755 patients, the frequency distribution of the major diagnostic groups was as follows:
LYMPHOMA TYPE
PERCENTAGE
Mycosis fungoides/SÚzary syndrome
82.3
Lymphomatoid papulosis
12.6
CD30+ anaplastic large-cell lymphoma
0.9
Peripheral T-cell lymphomas
2.9
B-cell lymphoma
4.5
AGE RANGE-MEDIAN  
SEX (M:F)
 
GEOGRAPHY
 
JAPAN  
The spectrum of cutaneous lymphomas in Japan: a study of 62 cases based on the World Health Organization Classification.

Department of Dermatology, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan.

J Cutan Pathol. 2006 Jul;33(7):487-91. Abstract quote

BACKGROUND: The relative incidence of malignant lymphoma subtypes differs according to geographic location. This study investigated the epidemiology of cutaneous lymphoma subtypes in Japan and compared it with other countries.

METHODS: Sixty-two patients with cutaneous lymphoma attending the Department of Dermatology, National Hospital Organization Hokkaido Cancer Center were reviewed. The World Health Organization classification of hematopoietic and lymphoid malignancies was adopted.

RESULTS: Of the 62 patients, 31 had primary cutaneous lymphoma (PCL) and 31 had secondary cutaneous lymphoma (SCL). T- and natural killer (NK)-cell lymphoma accounted for 80% of PCL, of which, mycosis fungoides accounted for almost 35%. Of the 31 patients with secondary cutaneous lymphoma, 17 patients (54%) had T- and NK-cell lymphoma, including nine adult T-cell leukemia/lymphoma patients, and 14 patients (46%) had B-cell lymphoma, including 11 diffuse large B-cell lymphoma patients. The majority of patients with SCL and NK-cell lymphoma with primary or secondary skin lesions had a poor outcome.

CONCLUSIONS: PCL in this study showed a similar incidence to that of other institutions in Japan, while also demonstrating different frequencies from that of other countries, suggesting that the relative frequency of different PCL subtypes differ according to geographical location, similar to previous reports of systemic malignant lymphoma.
Am J Dermatopathol 2001;22:510-514
Review of 65 pateint cases from 1988-1999 as classified by the EORTC found good correlation between histologic subtypes and clinical follow-up

 

PATHOGENESIS CHARACTERIZATION

T-cell receptor beta variable region (V beta) usage in cutaneous T-cell lymphomas (CTCL) in comparison to normal and eczematous skin.

Potoczna N, Boehncke WH, Nestle FO, Kuenzlen C, Sterry W, Burg G, Dummer R.

Department of Dermatology, University of Zurich Medical School, Switzerland.

J Cutan Pathol 1996 Aug;23(4):298-305 Abstract quote

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of lymphoproliferative disorders.

\We investigated the variable region (V beta) of the T-cell receptor (TCR) repertoire in CTCL and compared it to the V beta repertoire in normal and eczematous skin. We used a panel of 21 anti-V beta antibodies and investigated 84 biopsies of 71 CTCL patients (4 parapsoriasis en grandes plaques (PA), 1 lymphomatoid papulosis, 29 mycosis fungoides (MF), 13 Sezary syndrome (SS), 1 CD8+ CTCL, 11 pleomorphic CTCL (PLEO), 12 CTCL nor classified). Six biopsies of normal skin and 6 of eczematous skin lesions served as controls.

We determined the frequency of the V beta in normal and inflamed skin and compared it to the percentage of the respective V beta in the malignant clone of the CTCL patients. The percentage of the V beta positive CD4+ cells in relation to the total number of T cells in normal skin and inflamed skin differed from the distribution of the V beta families in the peripheral blood mononuclear cells (PBMC). Out of 71 CTCL cases, the clone was identified in 23 (32%).

We identified the following clones: 1 V beta 3.1 (16MF), 7 V beta 5.1 (1 CD8+ CTCL, 1 CTCL not classified, 1 MF, 1 PA, 3 SS), 1 V beta 6.7 (1 SS), 7 V beta 8.1/8.2 (2 CTCL not classified, 1 PLEO, 2 MF, 2 SS), 1 V beta 12.1 (1 PLEO), 3 V beta 17.1 (2 CTCL not classified, 1 MF), 2 V beta 22.1 (1 CTCL not classified, 1 MF), 1 TCR delta (SS). The frequency of the malignant clone V beta usage corresponded well to the repertoire of V beta in eczematous skin but not to the repertoire in PBMC.

In 6 patients, the malignant clone was mainly localized in the epidermis. In 17 cases, the clone-specific cells were distributed in epidermis and dermis equally. A retrospective analysis showed that preferential epidermal homing of the clone was associated with a non-aggressive clinical course. The V beta usage of CTCL and eczema suggests a special cutaneous microenvironment which might be co-created by certain (bacterial?) superantigens. A preferential epidermal homing of the clone might have prognostic implications.

Association of erythrodermic cutaneous T-cell lymphoma, superantigen-positive Staphylococcus aureus, and oligoclonal T-cell receptor V beta gene expansion.

Jackow CM, Cather JC, Hearne V, Asano AT, Musser JM, Duvic M.

Department of Dermatology, University of Texas Medical School, Houston, USA.

Blood 1997 Jan 1;89(1):32-40 Abstract quote

Forty-two patients with cutaneous T-cell lymphoma, including 31 with exfoliative erythroderma or Sezary syndrome and 11 with mycosis fungoides, were studied for the occurrence of staphylococcal infection.

Thirty-two of 42 (76%) had a positive staphylococcal culture from skin or blood. One half of the patients with positive cultures grew Staphylococcus aureus. This group included 11 with Sezary syndrome and 5 with rapidly enlarging mycosis fungoides plaques or tumors. All of the S aureus carried enterotoxin genes. Surprisingly, 6 of 16 strains were the same toxic shock toxin-1 (TSST-1)-positive clone, designated electrophoretic type (ET)-41. Analysis of the T-cell receptor V beta repertoire in 14 CTCL patients found that only 4 had the expected monoclonal expansion of a specific V beta gene, whereas 10 had oligoclonal or polyclonal expansion of several V beta families. All patients with TSST-1+ S aureus had overexpansion of V beta Z in blood and/or skin lesions.

These studies show that S aureus containing superantigen enterotoxins are commonly found in patients with CTCL especially individuals with erythroderma where they could exacerbate and/or perpetuate stimulate chronic T-cell expansion and cutaneous inflammation. Attention to toxigenic S aureus in CTCL patients would be expected to improve the quality of care and outcome of this patient population.

 

LABORATORY/
RADIOLOGIC
CHARACTERIZATION
PET SCAN  


Assessment of tumor burden and treatment response by 18F-fluorodeoxyglucose injection and positron emission tomography in patients with cutaneous T- and B-cell lymphomas.

Shapiro M, Yun M, Junkins-Hopkins JM, Vittorio CC, Schulman N, Saidman BH, Fried RG, Rook AH, Alavi A.

Department of Dermatology, University of Pennsylvania Health System, Philadelphia, USA.

J Am Acad Dermatol 2002 Oct;47(4):623-8 Abstract quote

18F-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is a unique functional/metabolic imaging modality that is efficacious in nodal staging and detection of extranodal involvement for a variety of lymphomas.

We report its novel use in evaluating tumor burden and response to therapy in two patients with cutaneous lymphomas. A 24-year-old woman with aggressive subcutaneous panniculitic T-cell lymphoma associated with fever, arthralgias, lymphadenopathy, mild anemia, and widespread painful lesions refractory to multiple treatment strategies exhibited intense uptake of a glucose analogue at sites of clinically apparent (and clinically imperceptible) disease. Denileukin diftitox therapy resulted in clinical remission, and a repeat PET scan failed to detect residual foci of malignancy. A 38-year-old man with a more indolent multifocal primary cutaneous follicle center B-cell lymphoma characterized by few systemic symptoms and slowly evolving lesions demonstrated only mild glucose analogue uptake at sites of disease. Remission was achieved by radiotherapy and intravenous rituximab, and confirmed by a repeat PET scan. Extracutaneous disease was not evident in either patient by this technique.

These preliminary data suggest that FDG-PET may be useful in determining disease activity at the time of initial diagnosis, after treatment, and evaluating a suspected recurrence.

 

GROSS APPEARANCE/
CLINICAL VARIANTS
CHARACTERIZATION
GENERAL  
WHO/EORTC classification of cutaneous lymphomas 2005: histological and molecular aspects.

Burg G, Kempf W, Cozzio A, Feit J, Willemze R, S Jaffe E, Dummer R, Berti E, Cerroni L, Chimenti S, Diaz-Perez JL, Grange F, Harris NL, Kazakov DV, Kerl H, Kurrer M, Knobler R, Meijer CJ, Pimpinelli N, Ralfkiaer E, Russell-Jones R, Sander C, Santucci M, Sterry W, Swerdlow SH, Vermeer MH, Wechsler J, Whittaker S.

Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

J Cutan Pathol. 2005 Nov;32(10):647-74. Abstract quote  

The new WHO/EORTC classification for cutaneous lymphomas comprises mature T-cell and natural killer (NK)-cell neoplasms, mature B-cell neoplasms, and immature hematopoietic malignancies. It reflects the unique features of lymphoproliferative diseases of the skin, and at the same time it is as compatible as possible with the concepts underlying the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. This article reviews the histological, phenotypical, and molecular genetic features of the various nosological entities included in this new classification. These findings always have to be interpreted in the context of the clinical features and biologic behavior.

Aim: To review the histological, phenotypical and molecular genetic features of the various nosological entities of the new WHO/EORTC classification for cutaneous lymphomas.

Methods: Extensive review of the literature cited in Medline and own data of the authors.

Results: The WHO/EORTC classification of cutaneous lymphomas comprises mature T-cell and NK-cell neoplasms, mature B-cell neoplasms and immature hematopoietic malignancies. It reflects the unique features of primary cutaneous lymphoproliferative diseases.

Conclusion: This classification is as much as possible compatible with the concept of the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. The histological, phenotypical and molecular genetic features always have to be interpreted in the context of the clinical features and biologic behavior.

Practical evaluation and management of cutaneous lymphoma

Maxwell A. Fung, MD
Michael J. Murphy, MD
Diane M. Hoss, MD
Jane M. Grant-Kels, MD

Farmington, Connecticut

J Am Acad Dermatol 2002;46:325-57 Abstract quote

Accurate evaluation of patients with suspected or known cutaneous lymphoma requires the integration of many sources and types of information, including clinical evaluation, microscopic analysis of tissue, immunophenotyping, gene rearrangement studies, clinical staging, and longitudinal observation. Diagnoses should be based on knowledge of specific lymphoma types as described in modern classification systems.

Management of patients with cutaneous lymphoma requires collaboration among dermatologists, dermatopathologists, hematopathologists, and medical, surgical and radiation oncologists.

WHO-EORTC CLASSIFICATION J Cutan Pathol 2010;37:516-524.
Primary Cutaneous T cell Lymphoma (CTCL) Non-Mycosis Fungoides  

Indolent

Primary cutaneous anaplastic large cell lymphoma
Primary cutaneous CD4+ small/medium sized pleomorphic T-cell lymphoma
Subcutaneous panniculitis-like T-cell lymphoma

Aggressive

Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma
Cutaneous gamma-delta T-cell lymphoma
Primary cutaneous T-cell lymphoma, unspecified
   
European Organization for Research and Treatment of Cancer (EORTC) Classification of Primary Cutaneous Lymphomas  
Primary Cutaneous T cell Lymphoma (CTCL)  
Indolent
MF
MF + follicular mucinosis
Pagetoid reticulosis
CTCL-Large Cell CD30+
Anaplastic
Immunoblastic
Pleomorphic
Lymphomatoid papulosis
CTCL-Aggressive
Sezary Syndrome
Large cell, CD30
(-)Immunoblastic
Large cell, CD30
(-)Pleomorphic
CTCL-Provisional
Granulomatous slack skin
Pleomorphic small/medium sized
Subcutaneous panniculitis-like T cell lymphoma

Primary Cutaneous B cell Lymphoma (CBCL)

 
CBCL-Indolent
Follicle center cell lymphoma
Immunocytoma (Marginal zone B-cell lymphoma)
CBCL-Intermediate
Large B-cell lymphoma of the leg
CBCL-Provisional
Intravascular large B-cell lymphoma
Plasmacytoma
T-Cell Rich B-Cell Lymphoma

 

HISTOPATHOLOGICAL VARIANTS CHARACTERIZATION
CD4- CD8- CTCL
CD4– CD8– `Double-Negative' Cutaneous T-Cell Lymphomas Share Common Histologic Features and an Aggressive Clinical Course

Dan Jones, M.D. , Ph.D. ; Francisco Vega, M.D. , Ph.D. ; Andreas H. Sarris, M.D. , Ph.D. ; L. Jeffrey Medeiros, M.D.

From the Division of Pathology and Laboratory Medicine (D.J., F.V., L.J.M.) and the Department of Lymphoma (A.H.S.), University of Texas–M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

Am J Surg Pathol 2002;26:225-231 Abstract quote

We report 15 patients with CD4–CD8– “double-negative” T-cell lymphoma arising in skin.

There were seven women and eight men with a mean age at diagnosis of 53 years (range 19–77 years). All but two patients presented with solitary or multiple cutaneous nodule(s). Initial and recurrent biopsy specimens showed a dense infiltrate centered in the mid-dermis (extending into subcutis when sampled) of small to intermediate-sized lymphocytes with indistinct nucleoli and frequently irregular nuclear contours. Periadnexal infiltration and epidermal ulceration were present in five cases with the intraepidermal cells being primarily reactive CD4+ T cells. All cases were negative for CD30 and terminal deoxynucleotidyltransferase; one showed expression of CD56, and six of eight tested cases were positive for T-cell receptor- expression.

Despite systemic chemotherapy, all 12 patients with clinical follow-up showed recurrent or progressive disease with widespread cutaneous dissemination in 10 of 12. Eventual dissemination to lymph nodes or bone marrow occurred in two patients each, with at least nine patients dead of disease or treatment complications. Only two patients achieved lasting clinical remission (with 2´-deoxycoformycin/pentostatin and nelarabine, respectively).

CD4–CD8– “double-negative” CTCL has distinctive histologic features and cytomorphology with a marked propensity for rapid multifocal cutaneous dissemination.

CD8+
Junctional CD8+ Cutaneous Lymphomas With Nonaggressive Clinical Behavior

A CD8+ Variant of Mycosis Fungoides?

Reinhard Dummer, MD; Jivko Kamarashev, MD; Werner Kempf, MD; Andreas C. Häffner, MD; Monika Hess-Schmid, MD; Günter Burg, MD

 

Arch Dermatol. 2002;138:199-203 Abstract quote


Objective
To evaluate the clinical and prognostic features in primary cutaneous CD8+ T-cell lymphomas, which are rare and considered to be aggressive cutaneous lymphoproliferative disorders.

Design
Single-center retrospective study.

Setting
Lymphoma clinic (referral center) of a university hospital.

Patients
Three patients presented with CD8+ cutaneous lymphoma characterized by a patchlike pattern and hyperpigmentation.

Results
Histological analysis revealed a CD3+, CD8+ small-cell infiltrate showing a remarkable affinity to the dermoepidermal junction zone. Clonality for the T-cell receptor chain was detected by polymerase chain reaction followed by denaturing gradient gel electrophoresis. The clinical presentation lasted several years (6 and 9 years, respectively) before the correct diagnosis was made. Treatment with nontoxic approaches (UV-B and local steroids) was successful. Aggressive clinical behavior was not observed.

Conclusions
Our 3 cases of junctional CD8+ cutaneous T-cell lymphomas were characterized by hyperpigmentation and nonaggressive clinical behavior. This type of lymphoma, which can be considered a CD8+ mycosis fungoides variant, must be distinguished from other types of cutaneous CD8+ lymphomas so that overtreatment can be avoided.


Clinical and pathological spectrum of CD8-positive cutaneous T-cell lymphomas.

Lu D, Patel KA, Duvic M, Jones D.

Departments ofHematopathology and Dermatology, UT-M.D. Anderson Cancer Center, Houston, TX, USA.

J Cutan Pathol 2002 Sep;29(8):465-72 Abstract quote

CD8+ T-cell lymphomas presenting in the skin are rare.

We describe the clinical and histological features of 18 patients with CD8+ cutaneous T-cell tumors, which have been divided into four groups. Seven patients had precedent long histories of rashes, which progressively spread in a presentation similar to that of CD4+ mycosis fungoides (MF).

Three patients had long-standing localized plaques consistent with a pagetoid reticulosis (PR) pattern. Two patients presented with erythroderma and had peripheral blood involvement consistent with a Sezary syndrome (SS) pattern and had rapidly progressive clinical courses. Six patients presented with cutaneous nodules of varying sizes and had variable outcomes, with two having rapidly progressive disease, two with indolent recurrences and a further two with complete responses to treatment. Histologically, 12 of the 18 cases showed an epidermotropic tumor infiltrate that was most marked in the three PR cases. Prominent periadnexal infiltration was seen in 11 cases. Similar to CD4+ MF, the skin-homing antigen, (cutaneous lymphocyte antigen: CLA), was strongly expressed in 13 of 16 tested cases. Expression of the cytotoxic granule protein granzyme B was noted in a majority of tumor cells in only three of 16 tested cases.

We conclude that approximately half of CD8+ cutaneous T-cell lymphomas clinically and histologically resemble CD4+ MF/SS, whereas presentation as discrete nodular lesions are more common in CD8+ tumors as compared to those that express CD4.

DUAL LINEAGE  
Primary Cutaneous Lymphoproliferative Disorders With Dual Lineage Rearrangement.

From the *Sikl's Department of Pathology, Charles University, Medical Faculty Hospital, Pilsen, Czech Republic; dagger
Dermatopathologische Gemeinschaftspraxis, Friedrichshafen, Germany; double daggerUnit of Dermatopathology, Department of Dermatology, Zurich University Hospital, Zurich, Switzerland; and section signDivision of Dermatopathology, Department of Pathology, Ohio State University Medical Center, Columbus, Ohio, USA.

 

Am J Dermatopathol. 2006 Oct;28(5):399-409 Abstract quote

We present a series of 15 cases of cutaneous lymphoma and pseudolymphoma with dual lineage rearrangement identified among approximately 1200 cases of cutaneous lymphoproliferative disorders assessed in our 4 institutions during the last 8 years in which the results of both T-cell receptor and immunoglobulin heavy chain rearrangement investigations were available.

On the basis of the clinicopathologic information, the cases were retrospectively subdivided into 2 categories: (1) cases with definite features of cutaneous lymphoma or pseudolymphoma (n = 11) and (2) cases with unclassifiable disease (n = 4). The detection of dual genotype in the first group did not influence the final diagnosis; 7 cases represented cutaneous B-cell lymphomas, 3 pseudolymphomas, and 1 case lymphomatoid papulosis. The presence of monoclonal T-cell receptor-gene rearrangements in these cases may be explained either by monoclonal or oligoclonal expansion of exuberant T cells (or B cells in case of lymphomatoid papulosis) or by lineage infidelity. Three patients with unclassifiable disease had several clinical and histopathologic features in common.

They were elderly, presented with solitary lesions, were in good general health and histopathologically demonstrated a dense multinodular infiltrate containing approximately an equal number of T and B cells and a high number of histiocytes forming granulomas, with prominent granulomatous features in 2 cases. B cells were either scattered with the infiltrate or formed collections vaguely resembling follicles; Reed-Sternberg-like cells were seen in 2 cases. B cells showed expression neither of immunoglobulin light chain. The T-cell component was represented mainly by small, well-differentiated lymphocytes or slightly pleomorphic cells, with some medium-sized convoluted cells. Epstein-Barr virus was not detected by polymerase chain reaction.

The exact classification of these cases is unknown; they differ histopathologically from previously published cases of bigenotypic cutaneous lymphomas. They may merely represent a growth or reactive pattern, but, on the other hand, may be low-grade lymphomas. If so, they may be histopathologically related to cutaneous Hodgkin disease, T-cell/histiocyte-rich large B-cell lymphoma, or composite lymphomas. Further reports are needed to identify these lesions to clarify their nature and biologic potential.
GRANULOMAS  


Cutaneous lymphomas with prominent granulomatous reaction: a potential pitfall in the histopathologic diagnosis of cutaneous T- and B-cell lymphomas.

Scarabello A, Leinweber B, Ardigo M, Rutten A, Feller AC, Kerl H, Cerroni L.

Am J Surg Pathol 2002 Oct;26(10):1259-68 Abstract quote

The presence of a granulomatous reaction in lesions of cutaneous lymphomas has been described in the past in several cases. Especially in mycosis fungoides, a "granulomatous" variant of the disease has been well characterized.

We studied the clinicopathologic features of cutaneous lymphomas with prominent granulomatous reaction, including both cutaneous T-cell lymphomas and B-cell lymphomas (primary cutaneous lymphoma 22, secondary cutaneous lymphoma one). Biopsies of 23 patients with histopathologic features of cutaneous T-cell lymphoma or cutaneous B-cell lymphoma with prominent granulomatous reaction were included in this study. A prominent granulomatous reaction was defined as the presence of a granulomatous component exceeding 25% of the dermal infiltrate.

There were 14 cases of mycosis fungoides, two of subcutaneous panniculitis-like T-cell lymphoma, four of small/medium pleomorphic T-cell lymphoma, one of follicle center cell lymphoma, one of large B-cell lymphoma, and one of secondary cutaneous peripheral T-cell lymphoma.

Altogether, a prominent granulomatous reaction could be observed in 1.8% of all patients with cutaneous lymphoma (primary or secondary) registered in the files of the Department of Dermatology of the University of Graz (Graz, Austria), demonstrating that there is a distinct, albeit small, proportion of cases revealing this peculiar reaction pattern. In seven cases a misdiagnosis of granulomatous dermatitis preceded the correct diagnosis for a period of 1-216 months, suggesting that sequential biopsies and complete phenotypic and molecular genetic analyses should be carried out in cases of "unusual" granulomatous dermatitis.

PLEOMORPHIC TYPE  

Localized cutaneous small to medium-sized pleomorphic T-cell lymphoma: A report of 3 cases stable for years.

von Den Driesch P, Coors EA.

Department of Dermatology, University of Erlangen-Nuremberg.

J Am Acad Dermatol 2002 Apr;46(4):531-5 Abstract quote

Small to medium-sized pleomorphic cutaneous T-cell lymphomas represent a provisional entity in the new European Organization for Research and Treatment of Cancer classification.

We describe 3 patients with a localized and outstanding stable variant of this tumor. A median follow-up period of 50 months did not reveal any spread into regional lymph nodes or to distant sites in any patient.

 

SPECIAL STAINS/
IMMUNOPEROXIDASE
CHARACTERIZATION
GENERAL  


An immunohistochemical study of CD4, CD8, TIA-1 and CD56 subsets in inflammatory skin disease.

Harvell JD, Nowfar-Rad M, Sundram U.

Department of Surgical Pathology, Stanford University Medical Center, Stanford, CA, USA.

J Cutan Pathol 2003 Feb;30(2):108-13 Abstract quote

BACKGROUND: Antibodies to CD4, CD8, TIA-1, and CD56 are available which perform well in formalin-fixed and paraffin-embedded tissue. While previous studies have investigated CD4 and CD8 subsets in inflammatory skin disease, few have specifically addressed TIA-1 and CD56 reactivity in benign dermatoses. Given that CD8, TIA-1, and CD56 are linked to aggressive lymphoproliferative disorders (i.e. subcutaneous panniculitic T-cell lymphoma, natural killer (NK), and NK/T-cell lymphomas), it would be important to determine their specificity for cutaneous hematologic malignancies. This investigation was undertaken to determine the frequency with which common, benign dermatoses express these four markers. We also sought to determine whether the ratio of CD4- to CD8-positive cells could be used to distinguish among the dermatoses, especially the superficial and deep perivascular ones.

METHODS: Formalin-fixed and paraffin-embedded sections from a variety of common inflammatory dermatoses were stained with antibodies to CD4, CD8, TIA-1, and CD56. Positive reactions were scored as a percentage of the entire mononuclear cell infiltrate.

RESULTS: All of the dermatoses represented in the study showed TIA-1- and CD56-positive lymphocyte subpopulations. On a case-by-case basis, the percentage of positive cells varied, and while all cases were positive for TIA-1, many were completely negative for CD56. For TIA-1, the percentage of positive cells ranged from 21 to 59%, and for CD56, from < 1 to 9%. The CD4:CD8 ratio ranged from 1.0 to 6.0 but was never less than 1.0. In addition to lymphocytes, TIA-1 also stained polymorphonuclear leukocytes, eosinophils, and mast cells.

CONCLUSION: TIA-1- and CD56-positive lymphocytes are common participants in routine inflammatory dermatoses, and therefore these markers are not specific for aggressive lymphoproliferative disorders. Using only immunohistochemical data, the ratio of CD4- to CD8-positive lymphocytes could not be used reliably to separate the superficial and deep perivascular dermatoses from one another. Finally, mast cells are positive for TIA-1 and are commonly seen in normal and inflamed skin, and thus TIA-1 is not specific for cytotoxic T lymphocytes.

CD5  
Cluster designation 5 staining of normal and non-lymphoid neoplastic skin

Bogner PN, Su LD, Fullen DR.

Department of Pathology, University of Michigan Medical Center, Ann Arbor, MI, USA.

J Cutan Pathol. 2005 Jan;32(1):50-4. Abstract quote

Background: Immunohistochemical staining for cluster designation 5 (CD5) has been found to label a variety of non-lymphoid tumors.

Methods: A variety of eccrine, apocrine, follicular, epithelial, and pagetoid lesions were selected and stained with an anti-CD5 monoclonal antibody (Novocastra Labs, Newcastle upon Tyne, UK, clone 4C7) by immunohistochemistry. The intensity of positive cytoplasmic staining was graded semiquantitatively (1+ weak staining, 2+ strong staining). Additionally, the percentage of positive lesional cells was placed in one of four categories: >75%, 25-75%, 1-25%, and <1%.

Results: Within normal skin, CD5 labeled lymphocytes, apocrine glands, deep dermal eccrine glands, and smooth muscle (weak). The majority of benign and malignant apocrine lesions demonstrated strong focal (36%, n = 11)-to-diffuse (64%, n = 16) staining. In contrast, labeling of benign eccrine tumors was more focal, tending to localize around ducts (79%, n = 19). Microcystic adnexal carcinoma demonstrated focal staining of deeper ductal structures (71%, n = 7), whereas desmoplastic trichoepithelioma and basal cell carcinoma showed only rare positive cells. All cases of mammary (n = 7) and extramammary (n = 8) Paget's disease labeled diffusely for CD5. Pagetoid Bowen's disease (n = 6), intraepidermal sebaceous carcinoma (n = 3), nor melanoma in situ (n = 6) showed any CD5 staining.

Conclusions: Immunohistochemical staining for CD5 is extremely useful in the differential diagnosis of pagetoid epidermal lesions and will mark mammary and extramammary Paget's disease, but not pagetoid Bowen's disease, melanoma in situ, or sebaceous carcinoma.
CD62L  
The application of a monoclonal antibody to CD62L on paraffin-embedded tissue samples in the assessment of the cutaneous T-cell infiltrates.

Magro CM, Sachdeva MP, Crowson AN, Barusevicius A, Baran PN, Kovatich AJ.

Department of Pathology, The Ohio State University, Columbus, OH, USA.
J Cutan Pathol. 2005 Jan;32(1):12-20. Abstract quote

Background: A reduction in the expression of the pan T-cell markers CD7 and CD62L supports an endogenous T-cell dyscrasia. Previously, clone availability for CD62L restricted its application to frozen tissue sections.

Materials and methods: A nonavidin/biotin technique to examine CD3, CD62L, and CD7 in paraffin formalin-fixed tissue in non-neoplastic and neoplastic T-cell infiltrates.

Results: In the reactive group, CD62L manifested a 15 and 22% reduction in epidermal and dermal staining, respectively; there was a 42 and 31% reduction in epidermal and dermal CD7 staining. In lymphomatoid hypersensitivity, CD62L showed a 24 and 9% reduction in epidermal and dermal staining, respectively; CD7 staining demonstrated reduced staining by 70 and 66% in the epidermis and dermis. In the non-lymphomatous endogenous T-cell dyscrasia and lymphoma categories, an 80% diminution in CD62L and CD7 expression was seen.

Conclusions: CD62L can be successfully applied in formalin-fixed tissue and exhibits enhanced specificity compared to CD7 in the evaluation of cutaneous T-cell infiltrates. Both CD62L and CD7 in paraffin-embedded, formalin-fixed tissue are useful diagnostic adjuncts, especially in regard to the discrimination of lymphomatoid hypersensitivity reactions from true endogenous T-cell dyscrasia.

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Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.


Commonly Used Terms

SALT-Skin-associated lymphoid tissue. Broad term used to describe native B lymphocytes within the skin. It is theorized that these lymphocytes may give rise to some CBCLs.

Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Got Path?
Recent teaching cases and lectures presented in conferences


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Last Updated May 26, 2010

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