Skin Lymphomas

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.

Epidemiology
Disease Associations
Pathogenesis
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Gross Appearance and Clinical Variants
Histopathological Features and Variants
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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/S�zary 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. Yasukawa K, Kato N, Kodama K, Hamasaka A, Hata H. 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

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. Kazakov DV, Kutzner H, Palmedo G, Boudova L, Michaelis S, Michal M, Vanecek T, Magro CM, Mukensnabl P, Dummer R, Burg G, Kempf W. 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.