Plaque Stage Mycosis Fungoides Research Articles

Cutaneous T-Cell Lymphoma Presenting with Atypical Perianal Lesions

A patient with an atypical presentation of cutaneous T-cell lymphoma is reported. For many years, there were perianal lesions only, which were initially diagnosed as a non-specific severe perianal dermatitis, possibly due to psoriasis. There was little response, however, to potent topical steroids. Further patch and plaque lesions then developed elsewhere and plaque stage mycosis fungoides was diagnosed, allowing effective treatment with superficial radiotherapy and PUVA to be given. The difficulties that may be encountered in the diagnosis of cutaneous T-cell lymphoma are discussed.

Localization of clonal T cells to the epidermis in cutaneous T-cell lymphoma

Mycosis fungoides (MF) is a form of cutaneous T-cell lymphoma (CTCL) characterized by progression of clonal, epidermotropic T cells with the proliferative (Ki-67+) T-cell fraction primarily confined to the epidermis in early CTCL. Our purpose was to determine whether the malignant clone (recognized by its clonal T-cell receptor [TCR] rearrangement) might also be localized to the epidermal compartment by differential Southern blot analysis. A rapid heat-saline technique was used to separately isolate epidermal and dermal DNA from 11 patients with CTCL (1 with disease in the pre-MF stage, 4 with patch-stage MF, 3 with plaque-stage MF, 1 with tumor-stage MF, 1 with Sézary syndrome, and 1 with non-MF peripheral T-cell lymphoma). Whole and heat-saline separated 6 mm biopsy specimens (obtained from the same lesion) were analyzed by standard Southern blotting with 5 to 10 micrograms of DNA digested with BamHI, HindIII, or EcoRI in each case. Filters were probed with a 32P-labeled TCR-C beta complementary DNA. Skin compartment localization of TCR-C beta rearrangement was compared with results of diagnostic immunophenotyping and expression of proliferating cell nuclear antigen. DNA yields were as follows: from the whole specimens, 14.5 to 62.5 micrograms; from epidermal sheets, 2 to 42.5 micrograms; and from the dermis specimens, 2.5 to 25.5 micrograms. Whole and separated specimens from one patient with plaque-stage disease, three with patch-stage disease, and one patient with pre-MF disease revealed no rearrangement. Six patients had detectable gene rearrangements in the whole specimen by Southern blot; four of six had identical rearrangements in only the epidermal fragment (including the Sézary syndrome biopsy specimen) and not the dermis. The other two patients had only dermal TCR-C beta rearrangement. No relation was seen between immunophenotype or proliferating cell nuclear antigen expression and the localization of TCR-C beta rearrangements. However, the degree of epidermotropism significantly correlated with the presence of TCR-C beta rearrangements in the epidermal sheets. This study demonstrates that the malignant clone in CTCL can be localized to the epidermal compartment in most cases in which a TCR rearrangement is detectable and that these clones are associated with epidermal proliferation of lymphocytes. This technique of differential epidermal versus dermal Southern analysis for TCR rearrangement may improve sensitivity by helping to distinguish reactive from malignant T-cell populations in future studies of the pathogenesis of CTCL.

Mycosis Fungoides Exhibits a Th1-Type Cell-Mediated Cytokine Profile Whereas Sezary Syndrome Express a Th2-Type Profile

We determined T-cell cytokine profiles in the epidermis, dermis, and blood of cutaneous T-cell lymphoma to differentiate whether unique cytokine profiles were associated with mycosis fungoides (MF) versus Sezary syndrome. Punch biopsy specimens from plaque stage MF (n = 7) were compared to Sezary skin (n = 3) after undergoing rapid heat-saline separation of epidermis from dermis. Normal adult skin (n = 11), neonatal foreskin (n = 4), untreated psoriatic plaques (n = 6), and normal donor peripheral blood leukocytes (n = 3) were studied as controls. Total RNA was extracted from all skin specimens, as well as peripheral blood leukocytes from MF (n = 3) and Sezary patients (n = 7), and was converted to cDNA by reverse transcriptase. Polymerase chain reaction amplification of cDNAs using interleukin 2 (IL-2), IL-4, IL-5, IL-10, and interferon gamma-specific primers was used to differentiate Th1-type responses (IL-2+ and interferon gamma +) from Th2-type responses (IL-4+, IL-5+, and IL-10+). beta-actin specific primers were included as a positive control for mRNA integrity. All MF specimens contained mRNAs for IL-2 and interferon gamma limited to epidermis but not IL-4, IL-5, or IL-10. In contrast, Sezary skin and blood showed a cytokine mRNA pattern dominated by IL-4, IL-5, and IL-10. MF blood showed a pattern similar to normal peripheral blood T cells with mixed detection of all T-helper cell cytokine mRNAs. All psoriasis samples contained mRNAs for IL-2 and interferon gamma in both epidermis and dermis with no IL-4 or IL-10 in either compartment. These findings demonstrate that the cutaneous lesions of MF are characterized by an epidermal Th1-type cytokine profile, whereas both the blood and skin of patients with Sezary syndrome is characterized by a Th2-type profile. This work suggests that differences in cytokine production may be related to the pathophysiology and clinical presentation in cutaneous T-cell lymphoma.

Adenosine deaminase activity in sera of patients with psoriasis, mycosis fungoides and adult T cell leukemia.

Adenosine deaminase activities in sera were measured in 18 psoriatic patients, 8 mycosis fungoides patients, and 9 patients with adult T cell leukemia. Adenosine deaminase activity in the sera of the psoriatic patients showed no significant increase. An elevated adenosine deaminase activity was observed in 7 of the 8 patients with mycosis fungoides and 8 of the 9 patients with adult T cell leukemia. After chemotherapy, adenosine deaminase activity in serum of acute adult T cell leukemia was reduced. Adenosine deaminase activity in the sera of 2 patients with smoldering adult T cell leukemia was more elevated, with exacerbation of the disease. It is difficult to grade the extension of the tumors in plaque stage mycosis fungoides and smoldering adult T cell leukemia. To know the progression of the disease is critical in determining its management. These results indicate that adenosine deaminase activity in serum is one of the reliable indicators for the grading of mycosis fungoides and adult T cell leukemia.

Treatment of Cutaneous T‐cell Lymphomas (CTCL) with Extracorporeal Photochemotherapy

Since August of 1988, we have treated seven CTCL patients with extracorporeal photochemotherapy, including two with tumor-stage mycosis fungoides (MF) showing mucinous degeneration, two with plaque-stage MF, and two with erythrodermatous MF. One was withdrawn just after the first trial. For each patient, the phenotypes of peripheral blood lymphocytes were analyzed by flow cytometry in terms of the percentages of OKT11, OKT3, OKT4, Leu9, OKT8, B1, Tac, OKT9, OKIa1, Leu7, Leu3a/4B4, and Leu3a/2H4 cells. These parameters were compared with the clinical responses according to skin score. The two patients with tumors died, but the five patients without tumors did not. Three of the 6 patients responded to the treatment. Side effects that are often associated with standard chemotherapy, such as bone marrow suppression, gastrointestinal symptoms and hair loss, were not observed. One cardiovascular event (1 patient) occurred. No significant changes in T-cell subsets were seen during the course of therapy. These preliminary data suggest that extracorporeal photochemotherapy may be effective for CTCL other than tumor-stage MF.

Treatment of a Case of Mycosis Fungoides and One of Parapsoriasis en Plaque with Topical PUVA Using a Monofunctional Furocoumarin Derivative, 4,6,4'‐Trimethylangelicin

A case of plaque stage mycosis fungoides and one of parapsoriasis en plaque were treated with topical PUVA therapy using a monofunctional furocoumarin derivative, 4,6,4'-trimethylangelicin (TMA). Both patients showed complete clearance of eruptions within 16 treatments. The therapeutic effectiveness of TMA was confirmed by the fact that those eruptions exposed to UVA alone, without TMA application, showed slower and less significant improvement. Histologically, dermal infiltrates of mycosis cells and associated epidermotrophism disappeared almost completely in response to TMA PUVA. No side effects or changes in values in laboratory examinations were observed during treatment.

Lymphomatoid papulosis: A follow-up study of 30 patients

Thirty patients, 13 female and 17 male, have been followed from 3 months to 22 years (mean, 81 months; median, 63 months) and special studies have been performed on a proportion of these in order to try to predict malignant evolution. Age at onset was from 20 to 70 years (mean, 43 years; median, 42 years). Duration of disease was from 1 to 30 years (mean, 119 months; median 161 months). Seven patients also had parapsoriasis en plaque or plaque-stage mycosis fungoides at the time of diagnosis and one patient had erythroderma. None of the 22 uncomplicated lymphomatoid papulosis patients developed malignant cutaneous lymphoma during the period of observation, while the remaining 8 patients who had concurrent parapsoriasis en plaque, mycosis fungoides, or erythroderma did not deteriorate further. Single-cell deoxyribonucleic acid (DNA) measurements on the dermal infiltrate were done in 13 patients and were abnormal in 7 patients. Two of these had greatly abnormal DNA histograms and at the same time an abnormal clinical presentation with multiple nodules and tumors. The remaining five patients had DNA histograms that indicated a potential for malignancy. Monoclonal antibody studies were performed on skin biopsy specimens of 10 patients. The dermal infiltrate was dominated by T-helper lymphocytes and some Hodgkin and Reed-Sternberg cells could be detected by the antibodies Ki-1, Ki-24, and Ki-27. Human T-lymphotropic virus type I (HTLV-I) antibodies were found in 3 of 18 patients examined. Treatment with psoralens plus ultraviolet A (PUVA) was effective (partial or complete remission) in six patients but they relapsed at cessation of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The Nature of Mycosis Fungoides

Thirty-four patients with a clinical diagnosis of plaque stage mycosis fungoides, poikiloderma atrophicans vasculare (poikiloderma) and parapsoriasis en plaques (parapsoriasis) were investigated for evidence of extracutaneous disease using a biochemical screen, blood films, bone marrow examination, chest radiograph, abdominal ultrasound, isotope liver scan, liver biopsy and lymphangiography. Skin biopsies were also taken from these patients and, in order to rule out non-specific histological change, from 29 controls with inflammatory skin disease; the slides were examined blind by two independent observers for evidence of mycosis fungoides or poikiloderma and graded accordingly. Both observers were able to differentiate significantly histological grades of mycosis fungoides corresponding to the clinical diagnosis although exact histological grades only corresponded on 35 per cent of slides. Features graded as classical or probable mycosis fungoides were found in between 22 and 67 per cent of patients with parapsoriasis and between 67 and 100 per cent of those with poikiloderma. We found no evidence of extracutaneous disease in any of our patients. Lymphangiograms were abnormal in 30 of 31 examinations but the changes were non-specific and did not correspond to disease type, duration or extent. Four patients had apparently unrelated co-existing disease including chronic lymphatic leukaemia in two, a monoclonal gammopathy and autoimmune haemolytic anaemia. This study shows that in its early stages mycosis fungoides is predominantly if not primarily a cutaneous disease. The findings also suggest that parapsoriasis and poikiloderma are part of the same disorder as mycosis fungoides or evolve into it. Aggressive treatment to prevent progression to mycosis fungoides plaque and tumour stage should therefore be tried. The findings support the idea that mycosis fungoides is a reactive rather than a neoplastic disorder.

Mycosis fungoides and Sézary's syndrome show distinct histomorphological features.

A light microscopic investigation of skin biopsy specimens from 10 patients with plaque stage mycosis fungoides (MF) and from 6 with Sézary's syndrome (SS) was carried out according to the defined histologic criteria, for the purpose of detecting some morphological characteristics of these diseases for their histological differentiation. This study revealed that some histomorphological differences regarding the epidermal and dermal changes, epidermotropism and the cellular infiltrate existed between MF and SS, and that these diseases were two distinct entities showing differences not only from a clinical and hematologic but also from the histological viewpoint.

Lymphomatoid Papulosis Associated With Plaque-Stage and Granulomatous Mycosis Fungoides

A 47-year-old black man had typical papulonodular lesions of lymphomatoid papulosis (LyP) with concurrent plaque-stage mycosis fungoides (MF). Both diagnoses were confirmed histologically. This supports the concept that LyP is part of the spectrum of cutaneous T-cell lymphoproliferative disorders. The patient also had a large nodule and a deeply infiltrated plaque, each of which exhibited a deep granulomatous reaction. These were interpreted as representing granulomatous MF. Clinically, there was an evolution from a predominance of LyP lesions to a predominance of MF plaques. Topical carmustine therapy resulted in a substantial decrease in the number and size of both LyP and MF lesions. Both lesion types involuted with hypopigmentation.

Quatitation of Dendritic Cells in Normal and Abnormal Human Epidermis Using Monoclonal Antibodies Directed Against Ia and HTA Antigens

Two monoclonal antibodies, NAI 34 and DA6 231, have been used as surface markers to count epidermal Langerhans cells in normal skin, allergic contact dermatitis, and mycosis fungoides of the plaque and poikilodermatous varieties. The antibodies recognized the HTA (human thymocyte antigen) and Ia antigens, respectively. In all situations the numbers of cells labeled by the two antibodies differed. In normal skin 75% of dendritic cells were labeled by both antibodies and 25% were labeled by NAI 34 alone. In contact dermatitis there is an increase in dendritic cells labeled by both antibodies and this pattern is also seen in untreated plaque stage mycosis fungoides. In poikilodermatous mycosis fungoides, striking staining of the epidermal keratinocytes with DA6 231 is seen with no dendritic cells labeled. Dendritic cells are, however, clearly seen with NAI 34 staining. Numbers of dendritic cells labeled by both antibodies fall during PUVA therapy.

Stimulation of Monocyte-Mediated, Antibody-Dependent Cytotoxicity in Mycosis Fungoides

Antibody-dependent cytotoxicity mediated by purified blood monocytes were determined in untreated patients with plaque-stage mycosis fungoides (MF), parapsoriasis en plaques, exfoliating erythroderma, and noncutaneous malignant lymphoma. Compared with healthy control subjects and control subjects with varicose ulcers, patients with MF had increased monocyte cytotoxicity. In the other dermatoses, normal monocyte cytotoxicity was found. Patients with noncutaneous malignant lymphoma showed normal or decreased monocyte cytotoxicity. There was no evidence that abnormal monocyte cytotoxicity in cutaneous and noncutaneous malignant lymphoma were caused by interaction with lymphocytes or serum. The presence of increased monocyte cytotoxicity in patients with plaque-stage MF may be a clinically useful finding when this diagnosis is suspected clinically but not proved histopathologically.

An unusual and fatal case of disseminated cutaneous herpes simplex

A patient with plaque stage mycosis fungoides (MF) developed an atypical disseminated cutaneous herpes simplex virus (HSV) infection manifested by polycyclic cutaneous ulcers. Although Tzanck preparations and serial antibody titers to herpes virus were negative, the diagnosis was readily established by viral culture and histologic examination of the skin lesions. Following adenine arabinoside therapy, the viral cultures of the ulcers became negative and the spread of virus-induced ulcerations ceased. In an immunocompromised host with rapidly advancing, sharply punched-out polycyclic cutaneous ulcerations, herpes simplex infection should be considered even though the classical vesicular lesions are absent.

Mycosis Fungoides With Underlying Epidermoid Cysts

The cause of epidermoid cysts is disputed, and many mechanisms have been proposed.^1,2One generally accepted theory is mechanical obstruction of the follicle such as seen in milia, acne cysts, and rarely in association with neoplasms, particularly nevocellular nevi.³Multiple epidermoid cysts of the face and scalp developed in a patient with mycosis fungoides. Histological examination exhibited extensive involvement of the hair follicles with dilation and cyst formation. Although this is an unusual phenomenon, its recognition is important since plaque-stage mycosis fungoides overlying epidermoid cysts may clinically mimic the tumor stage of the disease. The clinical picture may become even more deceptive since these cystic lesions would not be expected to respond to conventional therapy for mycosis fungoides. <h3>Report of a Case</h3> A 53-year-old man was admitted with the complaint of intense pruritus for two months. Twelve years before he had noted a patch of alopecia that slowly

Mycosis Fungoides Involving the Brain and Optic Nerves

In a patient with long-standing plaque-stage mycosis fungoides, eye pain, a visual field defect, decreased acuity, and a swollen optic disc developed. A lymphomatous infiltrate consistent with mycosis fungoides was found in the brain at craniotomy and in the optic nerves at autopsy. Ten months elapsed between the presenting symptoms and death and during this period the patient's symptoms were controlled with prednisone therapy. The optic nerves as well as the brain can be involved with mycosis fungoides.

Photochemotherapy for Mycosis Fungoides

Twelve cases of cutaneous mycosis fungoides (MF) with erythroderma, plaques, and tumors were treated with photochemotherapy. Methoxsalen followed two hours later by ultraviolet light (UVA) resulted in clinical clearing of skin lesions in seven patients with plaque stage MF and one patient with erythrodermic MF. Four patients with both plaque and tumor stage MF showed clearing of plaques but not the tumors. Phototherapy units consisted of boxes with 16 to 64 UVA lights. The mean numbers of treatments to clear was 17.4. The mean total dose to clear was 134.8 joules. The mean dose of maintenance UVA was 5.6 joules/sq cm. Histopathologic clearing of mycosis fungoides was demonstrated with the clinical clearing.