Hodgkin Lymphoma in a patient with mycosis fungoides: molecular evidence for separate cellular origins

We report the case of a man with mycosis fungoides (MF), who, 11 years after diagnosis, developed Hodgkin's disease. Although MF is associated with a higher than expected prevalence of other malignancies, including Hodgkin lymphoma, analysis of cells from the skin and lymph nodes showed findings that suggest a separate cellular origin for the two diseases.     

Mycosis fungoides associated with malignant melanoma and dysplastic nevus syndrome

BACKGROUND: The increased risk of second malignancies, including nonmelanoma skin cancers, in cutaneous T-cell lymphoma (CTCL) patients has been well documented. However, relatively few studies of malignant melanoma in CTCL patients have been reported. METHODS: A database of 250 CTCL patients registered over a 3-year period was searched to identify patients with diagnoses of both mycosis fungoides (MF) and malignant melanoma. RESULTS: We identified six cases of MF associated with malignant melanoma and one associated with dysplastic nevus syndrome, which is a marker of increased risk of melanoma. In four patients, melanoma was diagnosed along with or before MF. In the remaining two patients, MF was diagnosed prior to melanoma, although dysplastic nevi were noted at the time MF was diagnosed. These two patients received treatment for their MF (one with topical nitrogen mustard and another with radiation therapy and nitrogen mustard) prior to the histologic confirmation of melanoma. Six patients had early stages of MF (IA or IB), while one patient presented with simultaneous erythrodermic mycosis fungoides involving the lymph nodes as well as melanoma metastatic to the lymph nodes from an unknown primary. CONCLUSION: There is an elevated prevalence of malignant melanoma in MF patients compared to the general US population (P < 0.00001) with a relative risk of 15.3 for observing malignant melanoma in MF patients (95% confidence interval 7.0-33.8). Possible pathologic links between the two diagnoses include effects of mycosis fungoides therapies, immunosuppression secondary to mycosis fungoides, and genetic alterations in the p16 tumor suppressor protein.     

Mycosis fungoides and cutaneous Hodgkin''s disease in the same patient: a case report

We describe a case of a 34-year-old man who presented with a 10-year history of mycosis fungoides and recent onset of inguinal lymphadenopathy, fever, and cutaneous nodules on the right hip. Biopsy of the inguinal lymph node showed mixed cellularity Hodgkin's lymphoma. Biopsy of the pre-existing skin lesions showed mycosis fungoides, while that of the nodules on the hip revealed cutaneous Hodgkin's lymphoma. Immunohistochemical and molecular analysis demonstrated a null phenotype in the Reed-Sternberg cells of the Hodgkin's disease lesions, and a T-cell phenotype in the lymphoid cells of the mycosis fungoides lesions. He was treated with chemotherapy for Hodgkin's disease, which is in remission 11 years later. Topical nitrogen mustard and maintenance PUVA therapy have been used for the mycosis fungoides, which is also in remission.     

Mycosis fungoides associated with Mediterranean lymphoma

Summary Mycosis fungoides was observed in a 71-year-old male with mediterranean lymphoma, a B-cell malignancy. It is proposed that this association is not incidental since hypergammaglobulinaemia and even monoclonal gammopathies have repeatedly been described in cutaneous T-cell lymphomas. Mediterranean lymphoma might have resulted from (a) helper cell activities of tumor T-lymphocytes, (b) common antigenic stimuli, or (c) deranged T-B cooperation due to concomitant mycosis fungoides.     

UNILESIONAL MYCOSIS FUNGOIDES: CLINICAL, MICROSCOPIC AND IMMUNOPHENOTYPIC FEATURES

Seven cases are reviewed in which the histologic and immunohistologic features were those of mycosis fungoides, although the patients presented with solitary lesions which did not recur after local therapy (excision in six, radiotherapy in one), with follow-up of 10 months to 18 years. Immunophenotypic staining of paraffin-embedded tissue revealed a predominant T-lymphocyte proliferation in all cases, None of the four cases studied for BER-H2(Ki-1) were positive, in contrast to the "activated" types of spontaneously regressing lymphoid lesion, lymphomatoid papulosis and "Ki-1" lymphoma. Electron microscopy in one case demonstrated the highly convoluted nuclei of the T cells within the infiltrate. These seven cases represent examples of unilesional mycosis fungoides in which the disease has not recurred after therapy, despite features indistinguishable from those of typical generalised mycosis fungoides-type of cutaneous T-cell lymphoma.     

Mycosis fungoides and chronic lymphocytic leukaemia--composite T-cell and B-cell lymphomas presenting in the skin

Composite lymphomas involving cutaneous B-cell and T-cell lymphomas are very uncommon. We report here the unique circumstance of a patient with mycosis fungoides (primary cutaneous T-cell lymphoma) who later developed chronic lymphocytic leukaemia (B-cell lymphoproliferation, B-CLL), which presented in the skin (leukaemia cutis) as a composite lymphoma affecting an earlobe. The presence of both lymphoproliferative disorders was confirmed with immunophenotyping and the finding of both immunoglobulin gene rearrangements and T-cell receptor gene rearrangements in the ear and the same T-cell receptor gene rearrangement in a plaque lesion of mycosis fungoides on the arm.     

Skin is the frequent site for involvement of peripheral T-cell and natural killer cell lymphomas in Korea

We have studied the clinicopathological features of 19 Korean cases of peripheral T-cell and natural killer (NK) cell lymphomas, not including mycosis fungoides. Primary cutaneous involvement was demonstrated in eight of these 19 cases, and we recognized four clinicopathologic subtypes among these eight patients: nasal type NK/T cell lymphoma, three cases; primary cutaneous CD30 positive anaplastic large cell lymphoma, two cases; subcutaneous panniculitis-like T-cell lymphoma, one case; lymphoma with hydroa vacciniforme-like cutaneous lesions, two cases. We did not, however, encounter any cases of HTLV-associated adult T-cell lymphoma/leukemia, which is common in Taiwan and Japan. EBV-associated lymphoma is the most prominent type of peripheral T-cell and NK cell neoplasm involving the skin in Korea.     

Folliculotropic mycosis fungoides in a psoriatic patient under methotrexate treatment

Folliculotropic mycosis fungoides is a variant of mycosis fungoides with a worse prognosis than the classic form. It can be associated with follicular mucinosis. We report a case of folliculotropic mycosis fungoides developing in the months following methotrexate therapy in a psoriatic patient. This lymphoma did not regress after stopping the antipsoriatic treatment. There is a known relationship between the use of immunosuppressive therapies and the development of lymphoproliferative malignancies. However these lymphomas are mainly B‐cell non‐Hodgkin lymphomas associated with Epstein‐Barr virus. In our patient the short period of time from the beginning of the immunosuppressive treatment to the occurrence of the T‐cell lymphoma does not support a strong causal relationship between the drug intake and the development of mycosis fungoides. To the best of our knowledge, this is the first case of folliculotropic mycosis fungoides in a patient treated with methotrexate for psoriasis.     

Concurrent eosinophilic fasciitis and cutaneous T-cell lymphoma. Eosinophilic fasciitis as a paraneoplastic syndrome of T-cell malignant neoplasms?

Eosinophilic fasciitis has been reported to precede hematologic malignant neoplasms such as myelomonocytic leukemia, lymphocytic leukemia, and Hodgkin's lymphoma. In this case study, eosinophilic fasciitis occurred concurrently with cutaneous T-cell lymphoma (mycosis fungoides). The clinical diagnosis of eosinophilic fasciitis was based on painful sclerodermatous lesions on the extremities and trunk without acrosclerosis. There was histologic confirmation with edema and lymphocytic inflammation in the superficial muscular fascia and dermis. Deposition of immune reactants was found in the fascia and dermis. In addition, peripheral eosinophilia and circulating immune complexes were detected. The diagnosis of cutaneous T-cell lymphoma (mycosis fungoides) was based on extensive erythematous cutaneous plaques, dermal and epidermal lymphocytic atypia, loss of pan-T-cell immunologic markers, and a cutaneous lesional T-cell receptor beta-chain rearrangement by Southern blot analysis. Eosinophilic fasciitis may occur as a paraneoplastic syndrome associated with hematologic malignant neoplasms, including mycosis fungoides. Cytokines or lymphokines released by activated immunocytes, either malignant leukocytes or normal leukocytes reacting to malignant cells, may be responsible for the eosinophilia and sclerosis seen in these associated hematologic malignant neoplasms.     

Leucoderma associated with flares of erythrodermic cutaneous T-cell lymphomas: four cases. The French Study Group of Cutaneous Lymphomas

We describe four patients with erythrodermic cutaneous T-cell lymphomas (two with erythrodermic mycosis fungoides, and two with Sézary syndrome) who presented with extensive hypopigmented lesions that occurred during flares of their cutaneous disease. These cases must be distinguished from previously described hypopigmented mycosis fungoides where hypopigmented lesions were the sole manifestation of the lymphoma. In two cases a biopsy was performed on hypopigmented skin, showing an infiltrate of atypical lymphocytes with epidermotropism and absence of melanocytes, as in vitiligo. It is suggested that the hypopigmentation could be due to the cytotoxicity of tumour or reactional lymphocytes directed against melanocytes.     

Mycosis fungoides associated with intestinal mucosa-associated lymphoid tissue lymphoma

Coexistence of cutaneous T-cell lymphoma (CTCL) and a B-cell malignancy is rare. We report a case of mycosis fungoides (MF) associated with intestinal mucosa-associated lymphoid tissue (MALT) lymphoma, which is a low-grade B-cell lymphoma of marginal cell origin. To the best of our knowledge, there have been only two cases of coexistent CTCL and MALT lymphoma, and this is the first case with typical MF and intestinal MALT lymphoma. The coexistence in our case might be coincidental, but genetic predisposition and the immunoregulatory capacity of neoplastic T lymphocytes may be factors contributing to this association.     

Small malignant melanoma in patients with mycosis fungoides

An increased risk for a second malignancy has been reported in patients with mycosis fungoides. We describe two subjects with mycosis fungoides who developed small malignant melanoma after topical application of nitrogen mustard.     

Paraneoplastic pityriasis lichenoides in cutaneous lymphoma: case report and review of the literature on paraneoplastic reactions of the skin in lymphoma and leukaemia

Paraneoplastic dermatoses are non-neoplastic skin disorders which occur in the context of an underlying malignant neoplasm. The classic paraneoplastic dermatoses are mostly associated with solid internal malignancies. They only rarely occur in the context of nodal or primary cutaneous lymphomas. Apart from these classic paraneoplastic dermatoses, there are additional skin disorders reported to occur in close association with haematological and lymphoproliferative disorders which can thus be regarded as paraneoplastic manifestations. We report for the first time two patients with pityriasis lichenoides et varioliformis acuta in association with mycosis fungoides. In addition, we review the literature on paraneoplastic dermatoses of the skin which have been described in patients with leukaemias and primary cutaneous lymphomas.     

Concurrent mycosis fungoides and intravascular large B-cell lymphoma in a single patient

Mycosis fungoides (MF) is an indolent, uncommon, non-Hodgkin T-cell lymphoma of the skin. It classically presents with patches, plaques, and tumors and may rarely show spread to internal organs or bone marrow. Up to 7.5% of MF patients may be diagnosed with a second malignancy. Intravascular large B-cell lymphoma (IVLBCL) is an exceedingly rare non-Hodgkin B-cell lymphoma characterized by predominant growth of large neoplastic cells in the lumina of blood vessels. This case presents with an unusual confluence of two rare diagnoses, MF and IVLBCL, made more remarkable by the presence of both diagnoses on a single skin biopsy sample.     

Detection of Epstein-Barr virus genome in primary cutaneous T and B cell lymphomas and pseudolymphomas

The Epstein-Barr virus (EBV) genome has recently been identified in Hodgkin's disease (HD) and nodal non-Hodgkin's lymphomas (NHL). In order to elucidate the possible aetiopathogenetic role of EBV in benign and malignant lymphoproliferative disorders we investigated skin specimens from 24 patients with a primary cutaneous lymphoproliferative disorders (10 T-cell lymphomas 6 B-cell lymphomas and 8 pseudolymphomas) and from 22 normal individuals for the presence of EBV DNA using the polymerase chain reaction (PCR) technique and in situ hybridization (ISH) on formalin-fixed paraffin-embedded tissue sections. EBV DNA was identified by PCR in one of two cases of mycosis fungoides, in one of seven cases of pleomorphic T-cell lymphomas, in one case of centro-blastic (CB) lymphoma of six B-cell lymphomas, and in three of eight pseudolymphomas. The EBV genome was also found in 2 of 22 specimens of normal skin. The small EBV-encoded nuclear RNAs, EBERs, were not detected in any PCR-positive sample by ISH. Based on our PCR and ISH findings, EBV does not seem to play a significant role in the development of cutaneous lymphomas.     

Topical imiquimod as treatment for different kinds of cutaneous lymphoma

Imiquimod as a topical immune response modifier leads to a localized production of interferon and other cytokines. Apart from its use for genital warts it has therefore been used as treatment for different cutaneous neoplasms, including a few cases of cutaneous T-cell lymphoma. We treated 8 patients (4 with mycosis fungoides, 1 with CD30+ anaplastic large cell lymphoma and 3 with primary cutaneous B-cell lymphoma) with topical imiquimod. Therapy was started three times per week, in cases without response, the frequency was increased to a daily application. Two patients with mycosis fungoides and the patient with the CD30+ anaplastic large cell lymphoma had a complete clinical remission, the other two patients with mycosis fungoides did not show a response to imiquimod. Of the patients with cutaneous B-cell lymphoma, two reached a partial remission, one did not respond to therapy. Two patients had side effects such as erythema and pruritus which disappeared when the frequency of therapy was reduced. Our preliminary data show that imiquimod might be effective in some cases with therapy resistant lesions of cutaneous T-cell lymphoma as well as of cutaneous B-cell lymphoma, but more controlled studies are needed.     

Successfully treated Hodgkin's disease followed by mycosis fungoides: case report and review of the literature

We report the case of a 30-year-old man who had Hodgkin's disease of the nodular sclerosing type and subsequently developed mycosis fungoides. The Hodgkin's disease was treated with radiation therapy and chemotherapy, and the patient was in complete remission. Seven years later mycosis fungoides occurred and rapidly became progressive. Autopsy revealed that the mycosis fungoides involved multiple organs without any evidence of Hodgkin's disease. The possible significance of the association of these two diseases is presented.     

Two Pediatric Cases of Primary Cutaneous B-cell Lymphoma and Review of the Literature

Abstract:   Primary cutaneous lymphomas are rare in the pediatric population and most often represent mycosis fungoides or CD30+ lymphoproliferative disorders. Primary cutaneous B-cell lymphoma has rarely been reported in children, and in the past may have been mistaken for disseminated nodal disease or benign cutaneous lymphoid hyperplasias. We describe two cases of marginal zone primary cutaneous B-cell lymphoma in young males. Thus far both have been managed with local therapy. We review the literature of this rare malignancy.     

Cutaneous malignant melanoma in association with mycosis fungoides

We retrospectively analyzed the first 461 cases entered into our cutaneous lymphoma database and found 285 cases of mycosis fungoides. We also identified 6 cases of malignant melanoma, all of which were found in patients with mycosis fungoides. The crude rate of melanoma in the general population in England, United Kingdom, in 1998 was 8.8/100,000 in men and 11.4/100,000 in women. The incidence of melanoma found in our cohort of patients with mycosis fungoides was far higher, and in 4 of the 6 patients cannot be explained on the basis of prior therapy. The reason for this association is unclear, but this report emphasizes the risk of second malignancies for patients with cutaneous T-cell lymphoma and melanoma.     

The spectrum of cutaneous lymphomas in Japan: a study of 62 cases based on the World Health Organization Classification

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.