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Background
This category of skin lymphomas has the unifying trait of neoplastic T cells exhibiting positive expression of the CD30 (Ki-1) antigen. Included in this category are several disorders that were once thought to be distinct. It is now clear that cases of RAH are a variant of CD30+ lymphomas. All of the CD30+ skin lymphomas have a good prognosis if limited to the skin. However, if systemic involvement occurs, the prognosis is poor.
CD30+ Large cell lymphoma
Lymphomatoid Papulosis (LyP)
Regressing Atypical Histiocytosis (RAH)
1. Predominance (>75%) or large clusters of CD 30+ blast cells in the initial skin biopsy
2. Clinically no evidence of lymphomatoid papulosis, mycosis fungoides or another type of cutaneous lymphoma
3. No extracutaneous localization at presentationPrimary CD 30+ cutaneous T cell lymphomas generally occur in adults, compared with primary noncutaneous CD 30+ T cell lymphomas which usually occur in children and adolescents. They usually present as solitary or localized skin lesions. These are generally nodules or small tumors and occasionally ulcers. About 10% of patients have lesions not confined to one area. Complete or partial spontaneous regression have been reported.
Under the microscope, the skin biopsy shows dense non epidermotropic infiltrates of large CD 30+ tumour cells with round, oval or irregularly shaped nuclei, one or more prominent often eosinophilic nucleoli and characteristically abundant cytoplasm. Multinucleated cells, including Reed-Steinberg-like cells, are usually present. Mitoses are usually numerous. In most cases, the CD 30+ tumour cells show a cohesive growth pattern forming large clusters or nodules. Inflammatory cells are few, and are located at the periphery of these clusters. These tumor cells may be uniform in appearance (anaplastic) or may be pleomorphic in both shape and size, or resemble immunoblasts (nonanaplastic).
Immunohistochemistry and gene rearrangements show that most of these primary CD 30+ large cells are of T cell origin. They generally have a CD4 phenotype with variable loss of CD2, CD3 and CD5 antigens. Besides expressing CD3O, they are also positive for the cutaneous lymphocyte-associated antigen (LCA). They usually do not express CD15 (Leu Ml) and epithelial membrane antigen (EMA), the latter are findings typical for Hodgkin's disease. The pathologist must distinguish primary cutaneous CD30 lymphomas from nodal based CD30 positive lymphomas which have secondarily involved the skin. This occurs most commonly in children. Although not a consistent finding, systemic cases show expression of tyrosine kinase (ALK) while primary cutaneous lymphomas lack this expression.
Sometimes there is a considerable delay before the histological diagnosis is reached, as in this patient. Multiple biopsies are often required. Patients should be examined carefully and staged with chest X ray, CT scan of the abdomen and bone marrow biopsy to exclude systemic disease. In patients with solitary or localised lesions, excision and/or local radiotherapy is the treatment of choice. Systemic polychemotherapy does not result in a higher cure rate, longer disease-free interval or less recurrence compared to local radiotherapy or surgical excision for localized disease. It is given to patients with more generalized disease and those with systemic involvement. About 25% of primary CD 30+ cutaneous T cell lymphomas can spontaneously regress, it may be appropriate to postpone treatment for several weeks in those with recurrent disease.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Anaplastic lymphoma
Ki-1 Lymphoma
Primary Cutaneous Anaplastic Large T-cell lymphoma
DISEASE ASSOCIATIONS CHARACTERIZATION ATOPIC ECZEMA
CD30(+) cutaneous lymphoma in association with atopic eczema.
Fletcher CL, Orchard GE, Hubbard V, Whittaker SJ, Edelson RL, Russell-Jones R.
Department of Dermatopathology, St John's Institute of Dermatology, St Thomas' Hospital, London, England.
Arch Dermatol. 2004 Apr;140(4):449-54. Abstract quote
BACKGROUND: Chronic atopic eczema is not regarded as a precursor of malignancy, and, to our knowledge, there has been only one previous case report of CD30(+) cutaneous lymphoma in association with atopic dermatitis.
OBSERVATIONS: We report 4 cases of CD30(+) lymphoproliferative disease in young adult patients with active atopic eczema dating from early childhood. Three patients developed primary cutaneous anaplastic large cell lymphoma, of whom 2 developed systemic disease and 1 died. The other patient developed lymphomatoid papulosis type A, which resolved after withdrawal of cyclosporine therapy. No other patient had received immunosuppressive therapy. Three had been treated with phototherapy, and 2 of these patients exhibited positive immunostaining for p53 within a proportion of the tumor cell population.
CONCLUSIONS: Although we have not been able to establish a causative link, we believe that the association of these 2 conditions has not occurred by chance. Biopsies of lesional skin from subjects with atopic eczema exhibit a proportion of CD30 cells, and clonal transformation of this subpopulation might account for the CD30(+) lymphomas in our patients.BURN Primary CD30+ve Cutaneous T-cell Lymphoma Associated with Chronic Burn Injury in a Patient with Longstanding Psoriasis.
Yeung CK, Ma SY, Chan HH, Trendell-Smith NJ, Au WY.
*Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China; and daggerDepartment of Pathology, Queen Mary Hospital, University of Hong Kong, Hong Kong, China.
Am J Dermatopathol. 2004 Oct;26(5):394-396. Abstract quote
An increased incidence of lymphoma has been reported in psoriatic patients, but most cases are nodal B-cell lymphoma.
We report a unique case of CD30-expressing cutaneous T-cell lymphoma arising from underlying psoriatic plaque after intractable caustic burns and cellulitis in the palm of a patient with generalized chronic plaque psoriasis. Molecular studies confirmed a localized clonal T-cell expansion, and the lesion responded dramatically to multiagent chemotherapy.
The case highlighted the possible role of chronic systemic and local T-cell activation in the pathogenesis of primary CD30+ve cutaneous T-cell lymphoma, and the importance of histologic assessment in chronic nonhealing skin lesions.HODGKIN'S DISEASE Br J Haematol 1998;101:492
5% of cases occur in patients with LyPIMMUNOSUPPRESSION Posttransplantation primary cutaneous CD30 (Ki-1)-positive large-cell lymphoma
Deniz Seçkin, MD
Beyhan Demirhan, MD
Tülin Ouz Güleç, MD
Ünser Arkan, MD
Mehmet Haberal, MD, FACS
Ankara, TurkeyJ Am Acad Dermatol 2001;45:S197-9 Abstract quote
We describe the case of a 51-year-old female renal transplant recipient with primary cutaneous CD30-positive large-cell lymphoma of T-cell origin.
Cutaneous T-cell lymphomas are rarely reported in organ transplant recipients, and we believe they should be considered in the differential diagnosis of cutaneous neoplastic and infectious diseases affecting this patient group.
Cutaneous T-cell lymphoma developing in a patient on cyclosporin therapy.Kirby B, Owen CM, Blewitt RW, Yates VM.
Departments of Dermatology and Histopathology, Royal Lancaster Infirmary, Lancaster.
J Am Acad Dermatol 2002 Aug;47(2 Pt 2):S165-7 Abstract quote The use of cyclosporin in the transplant setting is associated with a small but significantly increased risk of the development of lymphoproliferative disorders. These are predominantly but not always related to Epstein-Barr virus (EBV) infection.
We report a cutaneous CD30(+) T-cell lymphoma in a patient with atopic eczema during low-dose cyclosporin monotherapy. There was no evidence of EBV DNA transcripts in the tumor tissue as assessed by in situ hybridization. The tumors resolved when cyclosporin therapy was stopped and have not recurred. There are a few reports of primary cutaneous lymphoma in transplant patients.
This is the first report to our knowledge of cutaneous lymphoma in a patient treated with low-dose cyclosporin monotherapy. Although this finding may be coincidental, we believe this case highlights the small lymphoproliferative risk associated with cyclosporin.
LABORATORY/
RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC LABORATORY MARKERS T-CELL GENE REARRANGEMENT
Department of Dermatology, University Hospital, Zurich, Switzerland.
Background: Detection of clonality has been reported to be a helpful tool in the diagnosis of cutaneous lymphomas. Monoclonal rearrangement of T-cell receptor genes (TCR) was reported in fresh frozen tissue of lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma (ALCL), but the diagnostic value of T-cell clonality in formalin-fixed, paraffin-embedded biopsies has so far not been assessed.
Methods: Detection of clonal rearrangement of TCRgamma genes by highly sensitive polymerase chain reaction-based automated high-resolution fragment analysis (AHRFA) in archival LyP (n = 18) and ALCL (n = 17) tissue.
Results: Detection of clonality differed significantly among the histologic forms of LyP as well as between LyP and ALCL with clonality found in none of the 10 biopsies of LyP type A and B, in 4/8 (50%) of the LyP type C specimens, and in 11/17 (65%) of ALCL cases.
Conclusions: T-cell clonality can only be found in a minority (four of 18; 22%) of archival LyP specimens, even when employing a highly sensitive detection method and is thus of limited diagnostic value. Final diagnosis of LyP has to be based mainly on clinical, histologic, and immunohistochemical findings rather than on results of clonality studies.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION General Most present with large tumors or nodules
HISTOLOGICAL
TYPESCHARACTERIZATION General Majority of CD30 cutaneous lymphomas are T cells but a minority show either null (non-T, non-B) or even B-cell phenotype
Department of Dermatology, Research Unit of Dermatopathology, Medical University of Graz, Graz, Austria.
Background: Primary cutaneous anaplastic large T-cell lymphoma (PCALCL) is a well-defined entity with prognostic differences from the nodal counterpart [nodal anaplastic large cell lymphoma (NALCL)]. Several histological variants of NALCL have been characterized (common, lymphohistiocytic and small cell). However, studies on morphological variants of PCALCLs are lacking.
Methods: We analyzed retrospectively the clinicopathologic features of 66 biopsies from 47 patients (M : F = 27 : 20; median age: 53 years; mean age: 51.8 years; range: 14-82) with PCALCL, in order to better characterize the spectrum of this unusual neoplasm. Results: The 'common variant' was the most frequent (40.4%). In contrast to NALCL, in PCALCL, marked reactive infiltrates are more commonly present. In fact, 26 cases were classified as 'inflammatory type' (15 cases) and 'lymphohistiocytic' (11 cases).
Concerning the predominant cell morphology, large anaplastic cells (33%) were almost as frequent as large pleomorphic (36%) and small to medium-sized cells (26%).
We reported for the first time in the skin 2 rare cases with the predominance of large cells with a 'signet-ring'-like appearance. Epidermotropism and presence of eosinophils were found in a proportion of cases in all PCALCL variants. Conclusions: PCALCL is characterized by variable histopathological presentations and a broad cytomorphologic spectrum.VARIANTS B-CELL
Primary cutaneous CD30 (Ki-1)-positive non-anaplastic B-cell lymphoma.Herrera E, Gallardo M, Bosch R, Cabra B, Aneri V, Sanchez P.
Departments of Dermatology and Pathology, University Hospital, School of Medicine, Malaga, Spain.
J Cutan Pathol 2002 Mar;29(3):181-4 Abstract quote BACKGROUND: The CD30 (Ki-1)-positive lymphoproliferative disorders show a non-epidermotropic infiltrate of large-sized pleomorphic T cells, being extremely rare those that develop from B cells.
CLINICAL CASE: A 51-year-old white man presented with a 8x10 cm lobulated scalp tumor that had developed during the previous 8 months. Histopathology demonstrated a proliferation of medium and large-sized non-anaplasic lymphocytes. The tumor cells (CD45+) expressed B phenotype (CD20+, CD3) and were CD30 (Ki-1) positive. The extension study revealed no extracutaneous involvement and the lesion resolved following chemotherapy. Two years later, after six cycles of chemotherapy that followed the CHOP protocol the patient remained asymptomatic.
CONCLUSIONS: We report a patient with a diffuse lymphoma of medium and large-sized B phenotype cells on the scalp that showed the unusual characteristic of being both non-anaplastic and CD30 (Ki-1) positive.
EOSINOPHIL RICH CD30+ LYMPHO-
PROLIFERATIVE
DISORDER OF
THE ORAL MUCOSAEosinophil-Rich CD30+ Lymphoproliferative Disorder of the Oral Mucosa A Form of "Traumatic Eosinophilic Granuloma"
Bachir Alobeid, MD, Lang-Xing Pan, MD, PhD, Laura Milligan, MSc, Leo Budel, MD, and Glauco Frizzera, MDAm J Clin Pathol 2004'121"43-50 Abstract quote
We describe 3 patients who had oral mucosal lesions with features of traumatic eosinophilic granuloma (TEG) and containing CD30+ atypical cells. In 1 patient, the oral lesion was followed by skin nodules. All lesions were evaluated histologically, by immunohistochemical analysis, and by polymerase chain reaction (PCR) analysis of the T-cell receptor (TCR) g chain gene.
All oral lesions were characterized by a dense and deeply infiltrative lymphoproliferation, showing epitheliotropism and massive eosinophilia. They contained atypical large lymphoid cells, which expressed T-cell markers and CD30. PCR analysis showed a monoclonal rearrangement of the TCR g chain gene in all lesions and, in 1 patient, the same rearrangement in the oral and cutaneous specimens.
The lesions in these patients seem to be the oral counterpart of the spectrum of primary cutaneous CD30+ lymphoproliferative disorders and should be recognized as such to avoid a diagnosis of large T-cell lymphoma and possible consequent overtreatment. However, they represent only a subset among several others within the complex and heterogeneous category of disorders referred to as TEG.NEUTROPHIL-RICH
Department of Pathology, Medical Faculty Hospital, Charles University, Pilsen, Czech Republic.
Cutaneous lymphomas co-expressing CD56 and CD30 are very rare. They share a clinicopathological overlap with natural killer- (NK)/T-cell lymphomas and anaplastic large-cell lymphomas (ALCLs), two entities with widely disparate clinical behavior.
We present a case of an immunocompetent 57-year-old Caucasian woman with a rapidly growing, angiodestructive and neuroinvasive primary cutaneous ALCL (PCALCL). The neoplastic population of large anaplastic CD30(+) and CD56(+) T cells was masked by a massive admixture of histiocytes and neutrophils. The partially ulcerated and pus-secreting tumor involved the forehead and scalp and was assessed as clinical stage IAE. After chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), the patient achieved a complete remission. Additionally, high-dose chemotherapy with autologous peripheral blood stem-cell transplantation was administered as a consolidation of complete remission, in which she has remained for 6 years.
This is the first CD30(+) and CD56(+) primary skin lymphoma to be reported on the head. The presented case carries a remarkable combination of clinicopathological features of PCALCL and NK-/T-cell lymphoma.
- Primary "Cutaneous" T-Cell Anaplastic Large Cell Lymphoma, CD30+, Neutrophil-Rich Variant with Subcutaneous Panniculitic Lesions, in a Post-Renal Transplant Patient: Report of Unusual Case and Literature Review.
Salama S.
From the Department of Pathology and Molecular Medicine, St. Joseph's Hospital and McMaster University, Hamilton, Ontario, Canada.
Am J Dermatopathol. 2005 Jun;27(3):217-223. Abstract quote
Posttransplantation lymphoproliferative disorders (PTLD) presenting clinically in the skin are rare and usually of B-cell phenotype.
Only 7 cases of cutaneous T-cell PTLD have been previously reported, mostly mycosis fungoides type, with no known cases of "cutaneous" presentation by CD30 (Ki-1) anaplastic large cell lymphoma (ALCL).The case reported is a 59-year-old male who developed multiple skin nodules on the right leg, 6 years following renal transplantation.
Initial biopsy showed ALCL involving the dermis with a background rich in neutrophils. The neoplastic cells were of T-cell phenotype, strongly CD30 with typical staining, and BCL-2 positive, but P53 negative. No EBV was detected by IHC, ISH, or DNA analysis. One year later, he developed painful subcutaneous nodules with surrounding erythema, resembling deep pustules or panniculitis, which on biopsy showed preferential involvement of the subcutaneous fat and prominent component of neutrophils. Twenty-two months following diagnosis, he died of cardiac failure with terminal myocardial infarct. There was however no clinical evidence of systemic spread of the lymphoma.
This report adds to the clinical and morphologic spectrum of these rare "cutaneous" lymphomas of T-cell lineage arising in the posttransplantation setting, and suggests that EBV does not play a role in their pathogenesis.
Neutrophil-rich anaplastic large cell lymphoma presenting in the skin.Kato N, Mizuno O, Ito K, Kimura K, Shibata M.
Am J Dermatopathol 2003 Apr;25(2):142-7 Abstract quote A neutrophil-rich anaplastic large cell lymphoma (ALCL) presented in the skin of a 47-year-old Japanese woman. The solitary cutaneous lesion was an eroded, 10-mm, dome-shaped nodule involving the skin of her left upper arm.
Histologically, it showed a proliferation of pleomorphic, anaplastic, large tumor cells with nuclei of various shapes, including embryo-shaped, Reed-Sternberg cell-like binucleated, and wreath-shaped multiple nuclei, in the dermis and subcutaneous tissues. There was an admixture of neutrophils ranging from about 30% to more than 50% per field. Immunophenotypically, the neoplastic cells were positive for CD30, CD4, leukocyte common antigen, anaplastic lymphoma kinase-1, epithelial membrane antigen, and granzyme B. She had no peripheral neutrophilia. The lesson was excised, and the site on the left upper arm was irradiated.
Six and a half months after diagnosis, however, swelling of a left axillary lymph node appeared; it also showed a proliferation of anaplastic large tumor cells admixed with numerous neutrophils ranging from about 25% to more than 60% per field. Southern blot analysis of T-cell receptor gene rearrangement revealed a clonal band. The patient was treated with six courses of cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy with complete remission.
Seventeen cases of neutrophil-rich ALCL arising in the skin, lymph node, muscle, testis, and skull bone were reviewed. This form may possibly be induced by trauma or irritation of conventional ALCL, although the true mechanism for the infiltration of neutrophils is still unclear.PSEUDO-EPITHELIOMATOUS
Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA.
Abstract quote
Pseudoepitheliomatous hyperplasia (PEH) in biopsies of CD30+ anaplastic large-cell lymphoma (ALCL) is present infrequently and is of unknown prognostic value and significance.
Our goal was to review the clinicopathologic features of cases of ALCL with PEH, study their course, and review the literature on the subject. Biopsy specimens of all cases of CD30+ lymphoproliferative disorders (59) were retrieved from the files of Yale Dermatopathology Laboratory over a 17-year period and reviewed.
We identified 4 cases of ALCL (7%) exhibiting prominent PEH. All 4 patients presented with 1 or 2 nodules. In 2 patients, the lesions spontaneously regressed within a few months after initial diagnosis. One patient chose to have an excision in which only a small number of CD30+ cells were present. We were unable to obtain follow-up for the fourth patient. In the spectrum of CD30+ lymphoproliferative disorders, cases of ALCL with PEH are infrequent. In addition to the 4 cases described here, in our review of the literature we found 35 cases of ALCL with PEH. Most of these patients present with 1 or a few lesions. In the majority of these cases, the lesions started showing evidence of clinical spontaneous regression and even complete resolution within a few months of initial diagnosis. The clinicopathologic correlation between ALCL and PEH has not been emphasized.
Because most of these cases follow a relatively benign clinical course, we recommend a more conservative approach in the clinical management of these patients.Primary cutaneous CD30 anaplastic large cell lymphoma with keratoacanthoma-like pseudocarcinomatous hyperplasia and marked eosinophilia and neutrophilia.
Lin JH, Lee JY.
Department of Dermatology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan.
J Cutan Pathol. 2004 Jul;31(6):458-61. Abstract quote
BACKGROUND: Pseudocarcinomatous hyperplasia (PCH) and marked tissue neutrophilia have been observed in cutaneous CD30(+) anaplastic large cell lymphoma (ALCL) occasionally and may cause misdiagnosis.
METHODS: An unusual case of CD30(+) ALCL of the skin resembling keratoacanthoma (KA) both clinically and pathologically was described. Histologic examination and immunostaining were performed.
RESULTS: A 55-year-old woman presented with a 3-month history of an enlarging hyperkeratotic tumor on the forehead with a central keratinous plug. Microscopic examination showed epithelial hyperplasia resembling KA and a diffuse background infiltrate of large atypical lymphoid cells in the dermis. The atypical cells resembled epithelial cells and were obscured by a massive infiltrate of eosinophils and neutrophils. Immunostaining confirmed the presence of a diffuse infiltrate of CD30(+) cells; these cells were negative for CD45RO, CD20, CD15, epithelial membrane antigen, anaplastic lymphoma kinase-1, and cytokeratin. There was no evidence of extracutaneous involvement. The findings were consistent with primary cutaneous CD30(+) ALCL of null cell phenotype with KA-like epithelial hyperplasia and marked eosinophilia and neutrophilia.
CONCLUSIONS: Our case illustrates that primary cutaneous ALCL may be associated with KA-like PCH and concurrent marked tissue eosinophilia and neutrophilia. Diagnosis in such cases is challenging both clinically and histologically because the large atypical lymphoid cells may easily be obscured by the massive infiltrates of eosinophils and neutrophils or confused with invasive squamous cell carcinoma.Pseudocarcinomatous change in lymphomatoid papulosis and primary cutaneous CD30+ lymphoma: A clinicopathologic and immunohistochemical study of 6 patients J Am Acad Dermatol 2001;44:239-47
6 cases of pseudoepitheliomatous hyperplasia (PEH) mimicking squamous cell carcinoma in association with an atypical CD30+ dermal infiltrate
Three patients had lymphomatoid papulosis type A, and 3 patients had cutaneous CD30+ lymphoma
All 6 cases showed histologic evidence of PEH with keratinocyte atypia and in 4 cases there was significant atypia to prompt a diagnosis of squamous cell carcinoma
Three of these received treatment with wide local excision and 2 had been engrafted
Immunohistochemical staining for epidermal growth factor (EGF) and transforming growth factor (TGF-) showed similar expression in lesional and perilesional skin
Epidermal growth factor receptor (EGFR) expression by the proliferating epithelium was similar to that of the suprabasal adjacent normal epidermis. There was no aberrant expression of EGF, TGF-, and EGFR by atypical lymphocytes
Cases demonstrate that PEH associated with CD30+ lymphoproliferative disease may closely resemble squamous cell carcinoma, thereby leading to inappropriate diagnosis and treatment
SPECIAL STAINS/
IMMUNOPEROXIDASECHARACTERIZATION CD44
Expression of CD44 and CD44v6 in primary cutaneous CD30 positive T-cell lymphoproliferative disorders.Liang X, Smoller BR, Golitz LE.
Departments of Pathology, University of Colorado School of Medicine, The Children's Hospital, Denver, CO, Department of Pathology, University of Arkansas for Medical Science, Little Rock, AR, USA.
J Cutan Pathol 2002 Sep;29(8):459-64 Abstract quote BACKGROUND: Expression of the lymphocyte homing receptor CD44 and its variant form, CD44v6, have been linked to unfavorable prognosis and tumor dissemination in non-Hodgkin's lymphoma. The role of CD44 and CD44v6 in primary cutaneous lymphomas may not necessarily correlate with that observed in nodal lymphomas. Our study attempts to evaluate the expression pattern of CD44 and CD44v6 in primary cutaneous CD30 positive T-cell lymphoproliferative disorders including primary cutaneous anaplastic large cell lymphoma (cALCL) and lymphomatoid papulosis (LyP) and compared the expression between these two subgroups.
METHODS: Immunohistochemical staining of CD44 and CD44v6 was performed on 10 cALCL and 18 LyP cases.
RESULTS: CD44 consistently expressed in all cases of primary cutaneous CD30 positive T-cell lymphoproliferative disorders. In contrast with previous studies, our results showed that CD44v6 expressed in 46% of all cases, including 50% cALCL and 44% LyP. There was no statistic difference in expression of CD44 or CD44v6 between cALCL and LyP subgroups.
CONCLUSIONS: These results provide a new evidence that CD44v6 is expressed in a subset cases of primary cutaneous CD30 positiveT-cell lymphoproliferative disorders and suggest that other factors or molecules rather than CD44 or CD44v6 are responsible for the difference between cALCL and LyP.
CD56
Large atypical cells of lymphomatoid papulosis are CD56-negative: a study of 18 cases
Jeff D. Harvell, Marmar Vaseghi, Yasodha Natkunam, Sabine Kohler and Youn KimJ Cutan Pathol 2002;29:88-92 Abstract quote
Background:Histologically, diffuse dermal infiltrates of large atypical lymphocytes can be seen in lesions as indolent as type C lymphomatoid papulosis (LyP) to ones as aggressive as NK/T-cell lymphoma. While lesions of lymphomatoid papulosis are definitionally positive for CD30, their ability to express CD56 has not been formally studied. The objective of the current study was to determine whether or not the large atypical cells of LyP express the natural killer cell marker, CD56.Methods:Biopsies from 18 patients with LyP were studied with monoclonal antibodies to CD30, CD56, CD8, and TIA-1. These included four type C LyP lesions. Clinical information was obtained by chart review and included extent of LyP lesions, presence/absence of disease at follow-up, and any associated hematologic malignancies.
Results:None of the biopsies exhibited CD56 positivity within the large atypical cells of LyP. While some biopsies demonstrated CD56-positive, small, presumably reactive, lymphocytes within the infiltrate, their presence did not correlate with extent of disease, persistence of disease, or propensity for an associated non-LyP hematologic malignancy.
Conclusions:The large atypical cells of types A and C LyP do not exhibit positivity for CD56, and thus a panel of antibodies that includes CD30 and CD56 can readily distinguish between the benign end of the spectrum of CD30-positive lymphoproliferations and aggressive NK/T-cell lymphoma.
Solitary primary cutaneous CD30+ large cell lymphoma of natural killer cell phenotype bearing the t(2;5)(p23;q35) translocation and presenting in a child.
Gould JW, Eppes RB, Gilliam AC, Goldstein JA, Mikkola DL, Zaim MT, Wood GS.
Department of Dermatology, Case Western Reserve University, and the Veterans Administration Medical Center, Cleveland, Ohio 44106, USA.
Am J Dermatopathol 2000 Oct;22(5):422-8 Abstract quote
Primary cutaneous CD30+ large cell lymphoma is an unusual tumor most commonly seen in adults. Most of these lymphomas are of T-cell origin and carry a good prognosis.
We present the case of a 4-year-old girl with stage IEA CD30+ large cell lymphoma with a CD56+ natural killer cell phenotype and the t(2;5)(p23;q35) translocation. After excision, the patient has been free of disease for 44 months. Primary cutaneous CD30+ large cell lymphoma is uncommon in children.
To our knowledge, primary cutaneous CD30+ natural killer type lymphoma has not been reported previously. The indolent behavior of this tumor indicates its similarity to other primary cutaneous CD30+ large cell lymphomas and its difference from other CD56+ lymphomas involving the skin, which often exhibit an aggressive clinical course.
Cases such as this one illustrate why the use of a single, or even a few, immunohistochemical stains can be misleading in regard to lymphoma classification and prognostication.
CLUSTERIN Clusterin Is Widely Expressed in Systemic Anaplastic Large Cell Lymphoma but Fails to Differentiate Primary From Secondary Cutaneous Anaplastic Large Cell Lymphoma
Marick E. Lae, MD
Iftikhar Ahmed, MD
and William R. Macon, MDAm J Clin Pathol 2002;118:773-779 Abstract quote
A recent study by Wellmann et al (Blood. 2000;96:398-404) detected clusterin expression in all 36 systemic anaplastic large cell lymphomas (ALCLs) tested, but not in any of 9 primary cutaneous ALCLs.
Our purpose was to confirm the diagnostic usefulness of clusterin in systemic ALCL and to evaluate its efficacy in distinguishing primary cutaneous ALCL from secondary skin involvement by systemic ALCL.We examined clusterin expression by paraffin immunohistochemical analysis in 41 systemic ALCLs (18 ALK-1+ and 23 ALK-1–), 9 primary cutaneous ALCLs, and 4 secondary cutaneous ALCLs. Clusterin was positive in 95% of systemic ALCLs (39/41), including 100% (18/18) of the ALK-1+ cases and 91% (21/23) of the ALK-1– cases. Five (56%) of 9 primary and 3 (75%) of 4 secondary cutaneous ALCLs were positive for clusterin.
Our observations confirm the diagnostic usefulness of clusterin in systemic ALCL, especially in the ALK-1– cases. However, our data fail to demonstrate its value in distinguishing primary from secondary cutaneous ALCL.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES CD30 CELLS IN REACTIVE DERMATOSES
Hospital de Clínicas, Department of pathology, Universidade Federal do Parana, Curitiba, Brazil.
BACKGROUND: Cutaneous infectious and inflammatory diseases may contain a significant number of CD30-positive cells, thus mimicking lymphomatoid papulosis (LyP) or anaplastic large cell lymphoma.
METHODS: We reviewed our cases of non-neoplastic skin conditions with large, CD30-positive cells and searched the literature for similar cases.
RESULTS: A total of 28 cases were included in the study: Milker's nodule (n = 8), Herpes simplex virus infection (n = 7), lymphomatoid drug reaction (n = 3), molluscum contagiosum (n = 3), nodular scabies (n = 2), leishmaniasis (n = 1), syphilis (n = 1), pernio (n = 1), ruptured infundibular cyst (n = 1) and pseudolymphoma in a scar (n = 1). CD30-positive cells were often arranged in clusters and revealed both Golgi and membrane positivity, similar to what was observed in LyP and CD30+ anaplastic large T-cell lymphoma.
CONCLUSIONS: Analysis of our data and of those published in the literature shows that viruses and drugs are the most common cause for occurrence of large CD30-positive cells in cutaneous pseudolymphomatous infiltrates. Arrangement of these large, CD30-positive cells in small clusters is not unique to cutaneous CD30-positive lymphomas, and in many cases a precise diagnosis can be made only upon accurate clinicopathological correlation or using ancillary methods such as polymerase chain reaction analysis for viral DNA.
CD30-Positive Atypical Lymphoid Cells in Common Non-Neoplastic Cutaneous Infiltrates Rich in Neutrophils and Eosinophils.Cepeda LT, Pieretti M, Chapman SF, Horenstein MG.
Am J Surg Pathol. 2003 Jul;27(7):912-8. Abstract quote CD30-positive cells characterize lymphomatoid papulosis and anaplastic large cell lymphoma but can also be found in nonneoplastic skin disorders. Purportedly, CD30 is useful in the differential diagnosis between insect bites and lymphomatoid papulosis.
Recently, a subtype of neutrophil-rich CD30-positive anaplastic large cell lymphoma has been described, which may enter the differential diagnosis of cutaneous neutrophil-rich inflammatory infiltrates.
We studied atypical CD30-positive lymphoid cells in five eosinophil-rich and 23 neutrophil-rich common nonneoplastic skin infiltrates. The eosinophil-rich cases included five insect bites. The neutrophil-rich cases included 9 inflammatory (hidradenitis suppurativa [n = 4], stasis ulcer [n = 2], ruptured cyst, rhynophyma, and Sweet syndrome); 12 infectious (bacterial [n = 8], viral [n = 2] and fungal [n = 2] etiologies); and 2 environmental (spider bites) cases. Atypical CD30-positive cells were found in 4 of 5 eosinophil-rich, 8 of 9 neutrophil-rich inflammatory, 6 of 12 neutrophil-rich infectious, and 2 of 2 neutrophil-rich environmental cases. Polymerase chain reaction analysis for B- and T-cell clonality and cell counts of neutrophils, eosinophils, plasma cells, B cells (using CD20), and T cells (using CD3) were performed in the cases that contained atypical CD30-positive lymphoid cells. CD30-positive cells averaged 4.8% of the cells counted in the areas where they were most concentrated. Of the 18 cases that amplified with polymerase chain reaction, all were polyclonal for T-cell receptor rearrangements; 10 were polyclonal and 8 oligoclonal for B-cell immunoglobulin rearrangements. There was no correlation between B-cell oligoclonality with CD30-positive cell counts, a particular disease, or a disease category.
In conclusion, the presence of CD30-positive atypical lymphoid cells in 71.4% of the common nonneoplastic cases studied, even in the presence of clonal B-cell populations, warrants caution in the interpretation of these cells as malignant, particularly when dealing with the differential diagnosis of lymphomatoid papulosis or neutrophil-rich anaplastic large cell lymphoma.LANGERHANS CELL HISTIOCYTOSIS
CD30 positive anaplastic large-cell lymphoma mimicking Langerhans cell histiocytosis.
Ezra N, Van Dyke GS, Binder SW.Department of Pathology and Laboratory Medicine, Division of Dermatopathology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732, USA.
J Cutan Pathol. 2010 Jul;37(7):787-92. Abstract
The presence of CD 1a+ dendritic cells (DC) has been well described in T-cell lymphoproliferative disorders, and the presence of large numbers of DCs has rarely been reported as a mimicker of Langerhans cell histiocytsis (LCH).
We present the case of a 56-year-old female with a solitary nodule on the chin whose case was referred to our institution for confirmation of the diagnosis of LCH. Skin biopsy showed an ulcerated nodule containing a wedge-shaped infiltrate comprised of large atypical cells and cells with prominent grooved nuclei. The constellation of histologic and immunologic features favored a CD30 lymphoproliferative disorder of T-cell lineage even though there were accompanying numerous dendritic histiocytes and CD1a positive Langerhans cells. The sheets of CD30 positive atypical lymphoid cells which express T-cell markers were consistent with CD30 positive lymphoproliferative disease and favor CD30 positive anaplastic large-cell lymphoma (ALCL) over Langerhans histiocytosis. The absence of Anaplastic Lymphoma Kinase (ALK) staining favored a primary cutaneous origin.
This case signifies a CD 30+ ALCL of the skin which histopathologically mimics a LCH.LYMPHOMATOID PAPULOSIS TUBERCULOSIS Atypical CD30+ cutaneous lymphoid proliferation in a patient with tuberculosis infection.
Massi D, Trotta M, Franchi A, Pimpinelli N, Santucci M.
Dipartimento di Patologia Umana ed Oncologia, Universita degli Studi di Firenze, Firenze, Italia.
Am J Dermatopathol. 2004 Jun;26(3):234-6. Abstract quote
We describe the case of a 65-year-old woman affected by a diffuse lymphadenopathy consistent with tuberculous infection who developed a papular eruption on the head and neck region.
Histopathologic examination of one papule showed an atypical CD30+ lymphoid infiltrate, which initially was cause of concern for the pathologists but was eventually regarded as reactive in nature. The case reported herein enlarges the spectrum of inflammatory infiltrates in which atypical CD30+ cells may be found. Since the reactive atypical CD30+ cells are morphologically similar to those cells observed in CD30+ lymphoproliferative disorders, including lymphomatoid papulosis, complete clinical history and laboratory findings are necessary to make the final and correct diagnosis.
Although the pathogenetic relevance of the presence of CD30+ cells within the cutaneous infiltrate of patients with systemic tuberculosis remains to be determined, our findings support the hypothesis that the cytokine profile associated with tuberculosis may not be strictly TH1-like, and that a TH1-like to TH2-like switch may also occur.VERRUCA VULGARIS AND ATYPICAL LYMPHOID INFILTRATE
Verruca Vulgaris With CD30-Positive Lymphoid Infiltrate: A Case Report
Anna M. Cesinaro, M.D.; Antonio Maiorana, M.D.
Am J Dermatopathol 2002; 24(3):260-263 Abstract quote
Expression of CD30 has been reported in reactive lymphoid cells that accompany some cutaneous viral infections. It is interpreted as a marker of lymphocyte activation in response to the infecting virus.We report on a case of viral wart presenting with an inflammatory infiltrate with numerous CD30+ atypical lymphoid cells. These cells comprised approximately 10% of the reactive cell population and showed a T-helper phenotype.
Infection by human papillomavirus should be included among the causes of cutaneous CD30+ reactive lymphoid infiltrates.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS
CD30+ cutaneous lymphoproliferative disorders: the Stanford experience in lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma.
Liu HL, Hoppe RT, Kohler S, Harvell JD, Reddy S, Kim YH.
Department of Dermatology, Stanford University, 900 Blake Wilbur Drive, Stanford, CA 94305, USA.
J Am Acad Dermatol. 2003 Dec;49(6):1049-58. Abstract quote
BACKGROUND: CD30+ cutaneous lymphoproliferative disorders (CLPDs) include lymphomatoid papulosis, borderline cases of CD30+CLPDs, and primary cutaneous anaplastic large cell lymphoma (PCALCL). Prior studies have shown CD30+CLPDs have an excellent prognosis.
OBJECTIVE: We sought to present the single-center experience of Stanford University, Stanford, Calif, in the management of CD30+CLPDs.
METHODS: A retrospective cohort analysis of 56 patients with CD30+CLPDs treated at our institution was performed.
RESULTS: No patients with lymphomatoid papulosis died of disease, and overall survival was 92% at 5 and 10 years. Disease-specific survivals at 5 and 10 years for PCALCL were 85%. Disease-specific survival at 5 years for localized versus generalized PCALCL was 91% versus 50% (P =.31). PCALCL was highly responsive to treatment, but the relapse rate was 42%. In all, 3 patients progressed to extracutaneous stage of disease. No clinical or histologic factors analyzed were predictive of worse outcome in lymphomatoid papulosis and PCALCL.
CONCLUSION: Similar to prior reports from multicenter European groups, the single-center experience at our institution demonstrates CD30+CLPDs have an overall excellent prognosis; however, cases of PCALCL with poor outcome do exist.Regressing atypical histiocytosis, a regressing cutaneous phase of Ki-1-positive anaplastic large cell lymphoma. Immunocytochemical, nucleic acid, and cytogenetic studies of a new case in view of current opinion.
Motley RJ, Jasani B, Ford AM, Poynton CH, Calonje-Daly JE, Holt PJ.
Department of Dermatology, University Hospital of Wales, Heath Park, Cardiff, United Kingdom.
Cancer 1992 Jul 15;70(2):476-83 Abstract quote
BACKGROUND. Regressing atypical histiocytosis is a rare multifocal cutaneous tumor characterized by large, spontaneously regressing, ulcerating skin nodules. Although initially self-remitting, the condition may progress to systemic lymphoma.
METHODS. Using material from one patient, an attempt was made to clarify the nature of this condition with immunophenotyping, genotyping, and chromosome studies.
RESULTS. Immunophenotyping studies indicated the condition was of T-cell lineage, although T-cell receptor gene studies showed polyclonal rearrangement. This case progressed to systemic lymphoma.
CONCLUSIONS. The authors believe regressing atypical histiocytosis is a regressing phase of Ki-1-positive anaplastic large cell lymphoma of the skin.
CD44 Association of Expression of CD44v6 With Systemic Anaplastic Large Cell Lymphoma Comparison With Primary Cutaneous Anaplastic Large Cell Lymphoma
Xiayuan Liang, MD
Loren E. Golitz, MD
Bruce R. Smoller, MD
Sandra J. Meech, MD
Lorrie F. Odom, MD
Sara A. William
and John W. Ryder, MDAm J Clin Pathol 2002;117:276-282 Abstract quote
CD44 is a ubiquitous multifunctional cell surface adhesion molecule family. High expression of the standard form, CD44s (CD44), and its variant form, CD44v6, has been reported to be associated with tumor dissemination in non-Hodgkin lymphoma.
To evaluate the potential role of CD44 and/or CD44v6 in different entities of anaplastic large cell lymphoma (ALCL), 30 cases of systemic ALCL (sALCL; 20 cases) and primary cutaneous ALCL (cALCL; 10 cases) were compared for expression of CD44 and CD44v6 by immunohistochemical staining. Expression of CD44v6 also was analyzed with respect to expression of anaplastic lymphoma kinase (ALK) in sALCL. No difference of CD44 expression was noted between sALCL and cALCL.
In contrast, expression of CD44v6 was found in 18 (90%) of sALCL cases and in 5 (50%) of cALCL cases. There was no correlation between expression of CD44v6 and expression of ALK in sALCL. These results indicate that expression of CD44v6 rather than CD44 correlates with sALCL. Furthermore, these results suggest that CD44v6 and ALK may be independent predictors of risk for the systemic phenotype of ALCL.
RECURRENCE Primary and secondary cutaneous CD30+ lymphoproliferative disorders: a report from the Dutch Cutaneous Lymphoma Group on the long-term follow-up data of 219 patients and guidelines for diagnosis and treatment.
Bekkenk MW, Geelen FAMJ, van Voorst Vader PC, Heule F, Geerts ML, van Vloten WA, et al.
Blood 2000;95:3653-61.
Primary cutaneous CD30+ ALCL has a high tendency to relapse in the skin
32 of 79 patients (41%) had one or multiple skin relapsesTREATMENT INTERFERON ALPHA Regression of multifocal, skin-restricted, CD30-positive large T-cell lymphoma with interferon alfa and bexarotene therapy
Lars E. French, MD
Michael Shapiro, MD
Jacqueline M. Junkins-Hopkins, MD
Carmela C. Vittorio, MD
Alain H. Rook, MDPhiladelphia, Pennsylvania
J Am Acad Dermatol 2001;45:914-8. Abstract quote
We report the case of a 43-year-old male patient with persistent multifocal, skin-restricted, CD30-positive, large T-cell lymphoma. Combination therapy of systemic interferon alfa and oral bexarotene was initiated on an experimental basis in the hope of circumventing therapies such as methotrexate, radiotherapy, or multiple-agent chemotherapy that may be required in such cases.
This treatment was associated with rapid and marked regression of the patient's cutaneous lesions.
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Last Updated July 9, 2010
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