Cutaneous Malignant Lymphoma Research Articles

Revisited improvement of specialized medical aid for patients with malignantcutaneous lymphomas

The authors analyzed the responses from directors of dermatovenerology institutions to a standardized questionnaire with questions about recording patients with malignant cutaneous lymphomas, follow-up care, diagnostics, treatment of patients, cooperation with experts in allied fields. They also revealed defects and problems in the organization of specialized medical aid for patients with malignant cutaneous lymphomas in the territory of the Russian Federation, and developed prospective methods for improvement of aid rendered to patients with malignant cutaneous lymphomas.

A Morphological Study of 608 Cases of Canine Malignant Lymphoma in France With a Focus on Comparative Similarities Between Canine and Human Lymphoma Morphology

This study reports cytomorphological, histomorphological, and immunological characterization of 608 biopsy cases of canine malignant lymphoma, with epidemiological and clinical data, collected from 7 French veterinary pathology laboratories. It compares morphological characteristics of malignant lymphoma in canines, per the updated Kiel classification system, with those reported in humans, per the World Health Organization (WHO) classification system. Of tumors described, 24.5% and 75.5% were classified as low- and high-grade malignant lymphomas, respectively. Presenting clinical signs included generalized or localized lymphadenopathy (82.4%) and extranodal diseases (17.6%) involving the skin (12.34%) and other sites (5.26%). Immunohistochemistry confirmed 63.8% B-cell (CD3-, CD79a+), 35.4% T-cell (CD3+, CD79a-), and 0.8% null-cell (CD3-, CD79a-) lymphomas. Most B-cell cases (38.49%) were of high-grade centroblastic polymorphic subtype; most T-cell cases (8.55%), high-grade pleomorphic mixed and large T-cell lymphoma subtypes. Some B-cell tumors showed morphologic characteristics consistent with follicular lymphomas and marginal zone lymphomas per the Revised European American Classification of Lymphoid Neoplasms and WHO canine classification systems and the WHO human classification system. Unusual high-grade B-cell subtypes included an atypical high-grade small B-cell lymphoma (0.66%), Burkitt-type B-cell lymphoma (1.64%), plasmacytoid lymphoma (0.99%), and mediastinal anaplastic large B-cell lymphoma (0.16%). Unusual T-cell subtypes included a previously undescribed high-grade canine immunoblastic T-cell type (1.15%), a rare low-grade prolymphocytic T-cell lymphoma (0.16%), and a recently described high-grade canine T-cell entity--aggressive granulocytic large-cell lymphoma (0.16%). Marginal zone lymphomas were common (10.86%); follicular lymphomas were rare (0.49%). Canine primary cutaneous malignant lymphoma subtypes were present (11.84%). There was no significant difference between B- and T-cell malignant lymphoma in regard to canine age and sex. A significant overrepresentation of Boxers (24.19%) was found for T-cell lymphomas.

Cutaneous lymphomas showing prominent granulomatous component: clinicopathological features in a series of 16 cases

The presence of a prominent granulomatous tissue reaction in skin biopsies from primary cutaneous or systemic malignant lymphomas with secondary cutaneous involvement is a rare but well-known phenomenon. This paper aims to characterize and study a series of cutaneous lymphomas showing a prominent granulomatous component. The clinical, histopathological and evolutive features of granulomatous variants of mycosis fungoides (5 patients, 2 of them associating 'granulomatous slack skin' features), Sézary syndrome (1 patient), CD30(+) cutaneous T-cell lymphoma (2 patients), CD4(+) small/medium pleomorphic cutaneous T-cell lymphoma (1 patient), primary cutaneous B-cell lymphoma (3 patients) and peripheral T-cell lymphoma with secondary epithelioid granulomatous cutaneous involvement (4 patients) were reviewed. The observed features were clinically non-distinctive. Only those cases presenting with granulomatous slack skin features were clinically suspected (2 patients). Non-necrotizing granulomata (11 patients) and granuloma annulare-like (4 patients) were the most frequently observed histopathological patterns. In five cases, no diagnostic lymphomatous involvement was initially observed. From our series, no definite conclusions regarding prognosis could be established. The diagnosis of cutaneous lymphoma may be difficult when a prominent cutaneous granulomatous inflammatory infiltrate obscures the true neoplastic nature of the condition. However, the presence of concomitant lymphoid atypia may help to suspect the diagnosis. In doubtful cases, the clinical evolution and the demonstration of a monoclonal lymphoid B- or T-cell population may lead to a definite diagnosis.

Low-Dose Palliative Radiotherapy for Cutaneous B- and T-Cell Lymphomas

To determine the efficacy of low-dose palliative radiotherapy for both low-grade malignant cutaneous B-cell lymphomas (CBCLs) and cutaneous T-cell lymphomas (mycosis fungoides). A total of 18 patients with low-grade CBCL (10 primary cutaneous marginal zone B-cell and 8 primary cutaneous follicle center lymphomas) with 44 symptomatic plaques and tumors underwent low-dose (4 Gy in two fractions) local radiotherapy. A total of 31 patients with mycosis fungoides were treated at 82 symptomatic sites, initially with 4 Gy and later with 8 Gy in two fractions. The complete response rate for CBCL lesions was 72%. Of the 44 B-cell lymphoma lesions, 13 were re-treated to the same site after a median of 6.3 months because of persistent (n = 8) or recurrent (n = 5) symptomatic disease. Of the mycosis fungoides patients treated with 4 Gy in two fractions (17 lesions), 70% failed to respond. Increasing the dose to 8 Gy in two fractions yielded a complete response rate of 92% (60 of 65 lesions). The patients in whom low-dose radiotherapy failed were retreated with 20 Gy in eight fractions. Our results have demonstrated that low-dose involved-field radiotherapy induces a high response rate in both CBCL and cutaneous T-cell lymphoma lesions without any toxicity. Therefore, this treatment is now our standard palliative treatment. At progression, it is safe and feasible to apply greater radiation doses.

Colchicine sensitivity index: a means of distinguishing benign and malignant lymphocytic cutaneous infiltrates (author's transl)

Lymphocytes in patients with chronic lymphatic leukaemia and other malignant lymphomas have an abnormally high sensitivity to colchicine in vitro. This can be expressed in a colchicine-sensitivity index and used diagnostically. Lymphocytes isolated from cutaneous infiltrates in mycosis fungoides, a cutaneous malignant T-cell lymphoma, had an increased colchicine-sensitivity index of 44 (P < 0.01). On the other hand, lymphocytes from cutaneous infiltrates of reactive inflammatory dermatitis cases had an index of 23. It would seem that the colchicine-sensitivity index is helpful in the diagnosis of selected cases of cutaneous malignant lymphomas.

Korrelation zwischen zytologischen und histologischen Haut-, Lymphknoten- und Milzbefunden bei 500 Hunden und Katzen

The results of 382 cytological examinations in dogs and 118 in cats were retrospectively compared with the correlating histological results.The histological diagnosis represented the gold standard. The investigation comprised skin, lymph node and spleen samples. The aim was to estimate the diagnostic value and the limits of cytological examinations in relation to the type of the changes. The cases were grouped in six categories: Corresponding diagnoses were formulated in 201 cases. In lymph node samples, they were reached almost twice as frequently than in skin and spleen samples. Round cell neoplasias (mast cell tumours, canine cutaneous histiocytomas and malignant lymphomas) were most often subclassified. Cytological diagnoses lacking subclassification were reached in 98 cases. The lesions were cytologically less precisely characterized than histologically. Provisional cytological diagnosis or differential diagnosis were formulated in 112 cases. Most commonly, the distinction between neoplastic and non-neoplastic character of a lesion was not possible (especially in mesenchymal spindle-cell proliferations). In 53 cases, the cytological diagnosis could not be established. In 22 cases, the relevant lesion was diagnosed only histologically whereas the cytological picture revealed another, usually secondary tissue reaction. Cytologically incorrect diagnoses were formulated in 14 cases.

Clinical, histopathological and immunophenotypical findings in five horses with cutaneous malignant lymphoma

This study documents the clinical, histopathological, immunohistochemical and flow-cytometric findings in five horses with cutaneous non-epidermotropic malignant lymphoma (ML). The median survival time after discovery of the first subcutaneous nodules was 3.8 years (range 2–5 years: n = 4). Histologically, the cutaneous ML had a pleiomorphic structure and contained a mixture of large reticulo-endothelial cells, medium-large sized lymphoid cells with a rounded nucleus and small nucleoli, many medium sized lymphoid cells with irregular nuclei, and some small lymphoid cells. Immunohistochemically (IHC) the lymphoid cells were positive for the pan-T-lymphocyte marker CD3 but negative for the B-lymphocyte markers CD21 and kappa and lambda immunoglobulin light chains. Although routine haematological examination revealed no abnormalities in the horses with cutaneous ML, changes in the peripheral blood lymphocyte population were apparent flow-cytometrically. Compared to clinically healthy horses, a decreased total percentage of cells was recorded in the lymphocyte gate. In three horses with cutaneous ML, an increase in CD4 positive cells was noticed in the monocyte gate. Flow-cytometric analysis of tumour cells collected by fine needle aspiration (FNA) suggested that the cutaneous MLs consisted primarily of CD4 and CD8 positive T-lymphocytes. The results were compared to those of a monomorphic multicentric T- and a monomorphic multicentric B-cell lymphoma. The results of immunohistochemistry and flow-cytometry were largely but not completely in accordance. In conclusion, the results of this study suggest that cutaneous non-epitheliotropic malignant lymphomas in the horse are of T-cell origin and that, after improvement of its accuracy, flow cytometric analysis of FNAs might become a useful aid to rapid tumour identification.

Cutaneous pseudolymphomas: a diagnostic challenge requiring clinical, histological, immunological and molecular analysis

Cutaneous pseudolymphomas (CPLs) are a group of benign lymphoproliferative conditions of the skin that histologically and, occasionally clinically, resemble malignant cutaneous lymphomas. CPLs may resemble cutaneous T-cell lymphomas or cutaneous B-cell lymphomas. The differentiation between benign and malignant lymphoproliferations can be challenging and requires a combination of clinical, histological, immunohistological and molecular analysis for accurate diagnosis. On rare occasions, absolute differentiation may not be possible. In this review, we discuss the histological techniques used in the evaluation of lymphoproliferations.

Dermatoonkologische Rehabilitation

National insurance companies in Germany support health cures for patients with malignant tumors (malignant melanoma, squamous cell carcinoma, Merkel cell tumor, malignant cutaneous lymphoma). The clinical requirements are an invasively growing tumor, problems of self-assurance, and dis-integration of the patient regarding his social and/or professional environment. The decision for a health cure is made by the treating dermatologist in the hospital. In this context, the following sociomedical criteria should be applied: impairment, disability, and handicap. Usually, rehabilitation starts after the patient is discharged from the hospital. The inpatient rehabilitation program should be performed at an institution capable of providing dermatological and psychological treatment. The dermatologist acts as a manager for the members of the rehabilitation team (psychologists, physiotherapists, social workers, and ergo-therapists). In conclusion, dermato-oncologic rehabilitation plays an important role in re-integrating the patient into his professional life to avoid retirement.

Phase II trial of oral suberoylanilide hydroxamic acid (SAHA) for cutaneous T-cell lymphoma (CTCL) unresponsive to conventional therapy

6571 Background: Epigenetic modulation of genes controlling apoptosis and differentiation is an attractive strategy for targeted cancer therapies. Suberoylanilide hydroxamic acid (SAHA), an oral inhibitor of class I and II histone deacetylases, induces apoptosis of malignant cutaneous T-cell lymphoma (CTCL) cell lines and Sezary Syndrome (SS) patients’ cells at clinically achievable doses. Methods: Thirty-seven advanced, refractory CTCL patients were treated with three oral dosing regimens of SAHA in a Phase II opened label trial. Results: Ten of 37 (27%) of patients, including 3 with large cell transformed tumors and 7 with SS, achieved a PR as evaluated by a physician global assessment score (> 50% reduction in disease burden). Lymphadenopathy decreased by more than 50% in 15 of 26 pts (58%), and pruritus in 21 of 31 pts (68%). Thirteen patients discontinued for progressive disease, and ten withdrew for adverse events of fatigue, anemia, rash, cutaneous neuropathy, leukopenia, weight loss (1 each), prior DVT with pulmonary embolism (2 pts), or thrombocytopenia (3 pts). The most common toxicities irrespective of grade were fatigue (27) or GI symptoms including diarrhea (21), nausea (19), dysguesia (17), dry mouth (14), and decreased appetite (13). Thrombocytopenia occurred in 21 of 37 pts (57%) at Gr 1 = 13, Gr 2 = 1, Gr 3 =3 and Gr 4 = 4 pts. Conclusions: Oral SAHA produced clinically meaningful partial responses (skin, nodes and blood) in 10 of 37 advanced, heavily pre-treated CTCL patients associated with decreased pruritus. The dosing regimen of 400 mg daily is undergoing confirmatory study in a phase IIb trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck Aton

Photodynamic therapy may be useful in debulking cutaneous lymphoma prior to radiotherapy.

Photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (5-ALA) is a promising new treatment for superficial malignant nonmelanoma tumours, including cutaneous malignant lymphoma. Here, we report a case of cutaneous anaplastic large cell lymphoma effectively treated by PDT with topical 5-ALA in combination with radiotherapy.

Cancer risk in women with previous breast cancer

Excess risks of several second neoplasms following breast cancer have been reported. However, these risks have still to be quantified. We considered 9,729 breast cancer patients registered by the Swiss Cancer Registries of Vaud and Neuchâtel (covering about 786,000 inhabitants) and followed up from 1974 to 1998. Overall, 443 second primary neoplasms (other than second primary breast cancers) were observed versus 389 expected [standardised incidence ratio (SIR): 1.14; 95% confidence interval (CI) 1.04-1.25]. The SIRs were above unity for endometrium (SIR = 1.5), ovary (1.3), colorectum (1.1), gallbladder (1.4), cutaneous malignant melanoma (1.4), kidney (1.4), lymphomas (1.4) and leukaemias (1.2), as well as for selected tobacco-related neoplasms. The largest excess risk was found for soft tissue sarcomas (STS) with 10 cases observed versus 3.1 expected (SIR = 3.2; 95% CI 1.5-5.9). Of these, eight occurred in potentially irradiated areas. This analysis confirms the existence of a modest excess in several neoplasms occurring after breast cancer. The substantial excess of STS confirms the strong association between irradiation and STS.

Feline cutaneous fibropapillomas: clinicopathologic findings and association with papillomavirus infection.

Twenty-three feline cutaneous fibropapillomas with histologic features similar to equine sarcoids were diagnosed. They were characterized by dermal fibroblastic proliferation with overlying, often ulcerated hyperplastic epidermis. Electron microscopic findings supported the fibroblastic nature of the neoplastic cells. The 23 tumors came from 20 cats and were submitted from veterinary clinics in Wisconsin and Minnesota. These tumors occurred most commonly in young cats and were found primarily on the head, neck, and digits. Fifteen of the 17 cats for which breed was reported were domestic shorthair cats. In 11/20 cases, there was confirmed exposure to cattle. Local recurrence of the tumor following surgical excision was reported in 7 of the 18 cats for which follow-up information was available. Metastasis was not documented in any of the cases. Two of the 19 tumors tested by polymerase chain reaction (PCR) had no amplifiable DNA. The remaining 17 were positive for papillomavirus by PCR. No papillomavirus DNA was detected in three other feline skin tumors (cutaneous mast cell tumor, malignant lymphoma, and fibrosarcoma) that served as controls. This is the first report of detection of papillomavirus in feline tumors that have clinicopathologic features similar to equine sarcoids.

Mycosis fungoides: classic disease and variant presentations.

Mycosis fungoides is a peripheral non-Hodgkin's T-cell neoplastic process, representing the most common type of primary cutaneous malignant lymphoma. Neoplastic lesions classically show skin predilection and characteristic clinical and histologic features in patch, plaque, and tumor stages. In addition, several clinicopathologic variants of mycosis fungoides have been delineated, including poikiloderma atrophicans vasculare (parapsoriasis variegata), Sézary syndrome, granulomatous mycosis fungoides, hypopigmented mycosis fungoides, folliculocentric mycosis fungoides, syringotropic mycosis fungoides, and Woringer Kolopp disease. We will review the salient features of patch, plaque, and tumor stage mycosis fungoides in this article and follow with a discussion of these variant clinicopathologic presentations and of therapeutic modalities.

Human pathogenic virus-associated pseudolymphomas and lymphomas with primary cutaneous manifestation in humans and animals.

The etiologic role of viruses in cutaneous lymphoproliferative disorders is still controversial. In benign cutaneous pseudolymphomas of the human skin, human T-cell leukemia/lymphoma virus (HTLV) type I (HTLV-I), varicella zoster virus, Epstein-Barr virus (EBV), and human herpesvirus (HHV) 6 (HHV-6) are the viruses most often identified, whereas in malignant lymphoproliferation human immunodeficiency virus type 1 (HIV-1), HTLV-I/II, and EBV are more common. Coinfections with more than one virus species have occurred in a number of cases. HHV-8 in association with a lymphoproliferative lesion appears to be indicative of a malignant cutaneous lymphoma rather than of pseudolymphoma. Negative results are of no diagnostic value because of the relatively low number of virus-positive cases: a considerable proportion of studies (with a large number of subjects) have documented virus-negative findings. Perhaps with the exception of HIV-1, findings of viral infections seem to indicate secondary rather than primary infections. Reports on animal models associated with human pathogenic viruses are scarce.

Differentiation of cutaneous malignant lymphoma and non-lymphoma using bromodeoxyuridine by occlusive dressing method

Differentiation of cutaneous malignant lymphoma and non-lymphoma using bromodeoxyuridine by occlusive dressing method

Cutaneous malignant lymphomas

Progress in understanding the pathogenesis of cutaneous lymphomas was the focus of a recent meeting ∗ ∗ The Clinically Oriented Symposium in Cutaneous Malignant Lymphomas of the European Society of Dermatological Research and the European Organization for Research and Treatment of Cancer was held at Charité, Berlin, Germany, on 24–28 October 1997. . Research in this area should improve diagnosis and treatment of these diseases, and aid the study of other T- and B-cell neoplasias

Cutaneous malignant lymphomas.

Abstract Progress in understanding the pathogenesis of cutaneous lymphomas was the focus of a recent meeting ∗ ∗The Clinically Oriented Symposium in Cutaneous Malignant Lymphomas of the European Society of Dermatological Research and the European Organization for Research and Treatment of Cancer was held at Charite, Berlin, Germany, on 24–28 October 1997.. Research in this area should improve diagnosis and treatment of these diseases, and aid the study of other T- and B-cell neoplasias

Primary cutaneous marginal zone B-cell lymphoma: a recently described entity of low-grade malignant cutaneous B-cell lymphoma.

Recently a new classification of primary cutaneous B-cell lymphomas (PCBCLs) has been proposed by the European Organization for Research and Treatment of Cancer (EORTC)--Cutaneous Lymphoma Project Group. The marginal zone B-cell lymphomas (MZLs) were not included as a distinct entity because of insufficient experience and controversial opinions. We have studied 32 patients (M:F ratio 1.5:1; age range 25-93 years; mean age 49.6 years; median age 50 years) to determine the diagnostic criteria of primary cutaneous MZL and the relationship with other low-grade malignant PCBCLs. For comparison, three patients with immunocytoma were included in the study. Clinically, patients presented with solitary or clustered reddish or red-brown papules, nodules, and plaques, sometimes surrounded by an erythematous halo. Histopathologic sections showed nodular or diffuse infiltrates involving the dermis and subcutaneous fat. Cytomorphologically small to medium-sized cells with indented nuclei and abundant pale cytoplasm (marginal zone cells, centrocyte-like cells) predominated. In addition, scattered blasts, lymphoplasmacytoid cells, and plasma cells were observed below the epidermis and at the periphery of the infiltrates. Reactive germinal centers were present in 75% of the cases. The three cases of immunocytoma showed a more monomorphous pattern with predominance of lymphoplasmacytoid cells. The marginal zone cells showed a CD20+, CD79a+, CD5- and Bcl-2+ immunophenotype. They expressed immunoglobulin G in the majority of the cases. Staining with the monocytoid B cell-related antibody KiM1p gave positive results in all specimens with a typical intracytoplasmic granular pattern. A monoclonal distribution of immunoglobulin light chains was observed in marginal zone cells in 75% of the cases. Germinal centers, when present, were either polyclonal or negative for both kappa and lambda light chains. Monoclonal rearrangement of the JH gene was detected via polymerase chain reaction (PCR) in 18 of 26 investigated specimens. Analysis in 12 patients of the bcl-2/immunoglobulin heavy chain gene rearrangement using PCR yielded negative results. Lesions were treated by surgical excision followed in some patients by local radiotherapy. Systemic antibiotic therapy was administered to three patients, with good response in two. The prognosis is excellent. After a mean follow-up of 47.9 months (range 6-252; median 24) all patients are alive without signs of systemic lymphoma. Primary cutaneous MZL represents a distinct clinicopathologic subtype of low-grade malignant PCBCL.

Search for Kaposi's sarcoma-associated virus DNA in hemangioproliferative disorders and cutaneous malignant lymphoma.

Recently, a Kaposi's sarcoma-associated herpesvirus (KSHV) was discovered. We evaluated by PCR 14 paraffin-embedded specimens with the histological diagnosis of endemic, classic and HIV-associated Kaposi's sarcoma (KS) for the presence of the KSHV DNA sequence. In addition, biopsies of adjacent, histologically unaffected skin, peripheral-blood mononuclear cells (PBMCs) of HIV-infected KS patients, PBMCs of one classic KS patient, and specimens of patients with hemangioproliferative disorders other than KS as well as samples of cutaneous T- and B-cell lymphoma were analyzed for KSHV. In all cases of KS, independent of the KS subtype, KSHV was detected in lesional skin. No KSHV was found in biopsies of the adjacent unaffected skin or PBMCs of HIV-infected KS patients. We found KSHV in the PBMCs of a patient with classical KS. All specimens of cutaneous T- and B-cell lymphomas or lymphomatoid papulosis were negative for KSHV. In addition, the samples with hemangioproliferative disorders other than KS were negative for KSHV. There was one borderline case of KS or acroangiodermatitis that was positive for KSHV. Additional histological sections and clinical evaluation confirmed the diagnosis of classic KS. In summary, the data indicate that PCR for KSHV should be a useful diagnostic tool in cases of hemangioproliferative disorders.