Involvement Of Mycosis Fungoides Research Articles

Img-PO-01 - The utility of multiparametric ultrasonography combined with selective core-needle biopsy in detecting lymph node involvement in mycosis fungoides

Img-PO-01 - The utility of multiparametric ultrasonography combined with selective core-needle biopsy in detecting lymph node involvement in mycosis fungoides

Acceleration of skin involvement may predict disease progression in early-stage mycosis fungoides: A retrospective cohort study

To the Editor: Many clinicians have observed that acceleration of body surface area (BSA) involvement in mycosis fungoides correlates with disease progression.1 The goal of this study is to quantify acceleration and determine if this parameter can predict progression and/or assure patients that they are unlikely to progress.

αEβ7 Expression Increases With the Extent of Cutaneous Involvement in Mycosis Fungoides.

Cell adhesion molecules are essential to lymphocyte migration in neoplastic and inflammatory skin diseases. Our aim was to investigate possible differences in cell adhesion molecule expression between mycosis fungoides (MF) and inflammatory skin diseases (drug reactions and allergic contact dermatitis). We selected 33 biopsies from patients with MF and 10 biopsies of patients with inflammatory skin diseases from Department of Pathology-Universidade Federal de São Paulo (UNIFESP) from January 1997 to December 2013. Expression of α4β1 integrin and αEβ7 integrin was assessed by immunohistochemistry in intraepidermal lymphocytes by counting 4 microscopic epidermal fields (×400) and comparing those between the 2 groups. We observed increased expression of integrin αEβ7 in intraepidermal lymphocytes in advanced stages of MF (T3 and T4). αEβ7 expression was detected in intraepidermal dendritic cells of MF and inflammatory diseases samples. The expression of E-cadherin in epidermal cells in MF outlined Pautrier microabscesses, whereas in inflammatory diseases, spongiosis reduced its expression in keratinocytes. The findings presented here support the idea that the lymphocyte migratory mechanism observed in neoplasms is similar to that of inflammatory processes of the skin.

Mycosis Fungoides of the Oral Cavity: Fungating Tumor Successfully Treated with Electron Beam Radiation and Maintenance Bexarotene.

Oral involvement in mycosis fungoides is unusual and portends a poor prognosis. The clinical findings of three new cases are described along with a differential diagnosis and review of the literature. For brevity, only one patient is discussed in detail below whereas the other two cases are solely described in table form. The patient had a four-year history of mycosis fungoides before developing an exophytic tongue tumor. He was treated with local electron beam radiation and is disease-free to date while being on maintenance therapy with oral bexarotene. Analysis of the data collected from our review of the literature and the present cases reveal key insights.

Conjunctival Involvement of T-Cell Lymphoma in a Patient with Mycosis Fungoides.

Background. Ocular involvement in mycosis fungoides (MF) cases occurs in one-third of patients with the eyelid being the most frequent site affected; however, conjunctival involvement is rarely reported. Herein, we report a rare case of conjunctival involvement of MF. Case Presentation. A 66-year-old man who was previously diagnosed with MF in 2010 and was treated presented in 2014 complaining of foreign body sensation and redness in both eyes. Slit lamp examination of both eyes showed erythematous conjunctival growth that extended circumferentially. Physical examination revealed erythematous skin lesions on different body parts. Conjunctival biopsy was performed and revealed a dense, highly polymorphic lymphocytic population. The immunophenotype demonstrated a neoplastic T-cell origin consistent with MF. A diagnosis of conjunctival involvement by MF was made. The conjunctiva was treated with radiotherapy resulting in tumor regression. There were no recurrences at the 6-month follow-up. Conclusion. T-cell lymphoma should be considered in patients with a history of MF presenting with conjunctival and skin lesions.

Systemic involvement in mycosis fungoides

Mycosis fungoides (MF) represents almost 50% of all primary cutaneous lymphomas and more than 70% of cutaneous T-cell lymphomas (CTCL). Arising from preferentially skin-homing lymphocytes with genetic instability, MF evolves through stages (IA-IVB), producing inconspicuous inflammatory features in the beginning and finally resulting in a proliferation of cytomorphologic, phenotypic, and genotypic abnormal tumor cells. Over the past 200 years, there has been much confusion in the classification of lymphomas due to semantic disagreements (MF, CTCL, parapsoriasis, lymphosarcoma, reticulum cell sarcoma, and many other terms), lack of diagnostic standard criteria, and new molecular diagnostic methods. Studies on extracutaneous involvement in early stages (IA-IIA) are almost completely lacking. In advanced stages of MF (IIB-IVB), discovery of extracutaneous involvement is dependent on the methods used (physical examination, technology, molecular diagnostics, autopsy, and laparoscopy) and reveals a wide range of results. Due to the inflammation-simulating features in the beginning of the disease, early diagnosis is very difficult to assess. Extracutaneous involvement has previously been documented in more than 70% of autopsies. More recent studies give much lower figures. Like all lymphomas, MF is a systemic disease from the very beginning, with distinct homing preferences in tumor cells. Organs most commonly involved during the lengthy course of the disease are, in descending frequency, lymph node/peripheral blood, liver, spleen, lung, bone marrow, GI tract, pancreas, and kidney.

Central nervous system involvement in mycosis fungoides: relevance of tcr gene testing in cerebrospinal fluid

IntroductionMycosis Fungoides (MF) is a rare malignant T-cell lymphoma, involving mainly the skin. In 50%–75% of cases, it can involve organs other than skin, with a 11%–14% Central Nervous System involvement (CNS).Case reportA 82-year-old woman presented to our Department with a 15-years history of MF with skin lesions. Neurological examination showed dysarthria and a left facio-brachial-crural hemiparesis. A CT scan showed a right fronto-rolandic lesion. A MRI, including DWI, confirmed the presence of the “neoplastic” lesion with slight hemorrhagic component and leptomeningeal contrast enhancement. Molecular TCR rearrangement test by PCR analysis was performed on skin biopsy, showed the presence of a single peak which fits with a monoclonal TCRG gene rearrangement (size 67). Molecular TCR test was also performed on the cerebrospinal fluid (CSF), which confirmed the presence of lymphocyte clone T g/ more expressed with the same size of that observed in the skin biopsy A total body CT scan did not show any lymphnodal or extranodal disease. The patient died after ten days.ConclusionMF usually occurs in the context of advanced and often histologically transformed cutaneous disease. Isolated CNS involvement is remarkably rare. This case highlights the need for regular neurologic follow-up after the diagnosis of MF, in particular when features that suggest risk of disease progression are present. Furthermore, the analysis of the skin biopsy and above all of CSF by PCR technique, based on our experience, should always be executed in MF patients with signs or symptoms suggesting CNS involvement.

CD25+ folliculotropic Sézary syndrome with CD30+ large cell transformation

Folliculotropic Sézary syndrome is a rare and unique variant of cutaneous T-cell lymphoma (CTCL) characterised by both follicular and leukaemic involvement of mycosis fungoides (MF). It is associated with a more aggressive clinical course and fatal outcomes. Large cell transformation (LCT) of mycosis fungoides/Sézary syndrome is also associated with an aggressive disease course and shortened survival, requiring an intensive therapeutic approach. This report describes a case of folliculotropic Sézary syndrome with CD30+ LCT. Most of the larger lymphocytes in the lesions were positive for CD25, the expression of which is associated with advanced CTCL. In addition, we review the literature on this unusual CTCL and provide evidence that this entity represents a distinct clinicopathological entity occasionally associated with extracutaneous involvement and LCT.

Uncommon presentation of mycosis fungoides: Eyelid margin involvement

Mycosis fungoides is a cutaneous T-cell lymphoma that has been rarely reported to involve ocular structures. A 33-year-old woman who had received therapy for mycosis fungoides on the trunk for 11 years, presented to our clinic with new plaques and tumors on her eyebrows and eyelid margin, and alopecia of her eyelashes and eyebrow. The histopathological examinations supported the diagnosis of mycosis fungoides. There was no intraocular involvement with tumor. The mycosis fungoides was of stage II B, and the patient was referred to medical oncology and radiation oncology clinics for treatment. She was placed on a radiotherapy schedule. The involvement of mycosis fungoides in the ocular area is rare in the published work. The importance of eye involvement is being seen in advanced cases, and there is a possible association between mycosis fungoides and poor prognosis by being an indicator of systemic involvement.

Central nervous system involvement in patients with mycosis fungoides and cutaneous large-cell transformation

Central nervous system (CNS) involvement in mycosis fungoides (MF) is a rare occurrence with devastating consequences. Large-cell transformation (LCT) of MF is associated with a poor prognosis and increased extracutaneous manifestations. In this report, we present 5 patients with MF, LCT, and CNS disease to better define their presentation, treatment, and prognosis and present critical differences they have compared with their nontransformed counterparts. We found that patients with LCT and MF are at increased risk of CNS involvement. In addition, whereas patients with nontransformed MF typically have significant skin and visceral involvement at the time of CNS disease, some patients with LCT have no extracutaneous symptoms and their skin MF is in remission at the time of CNS presentation. Transformed patients tend to present with speech and visual difficulties secondary to mass lesions. Therefore, we recommend at least annual screening of patients with transformed MF for CNS disease with head computerized tomography with orbital cuts.

Central Neurologic Involvement in Mycosis Fungoides

Neurologic involvement in mycosis fungoides is rare. Isolated case reports in the literature suggest the pattern and the natural history for such occurrences, while a literature summary can provide direction on diagnosis and management. Although case series may confirm such information, cohort data are required to establish an overall risk of occurrence and to evaluate possible predictive factors. We presented a case of central nervous system involvement in mycosis fungoides from Haifa, Israel and tabulated a series of nine cases from Canada. To estimate the risk of neurologic involvement, a cohort of 680 consecutive patients with newly diagnosed mycosis fungoides, of which the nine cases of neurologic involvement emerged during follow up, was analyzed using the Kaplan-Meier method. The actuarial risk of developing neurologic involvement was related to the baseline tumor-node-metastasis-blood classification factors. The pattern of disease in these 10 additional cases confirms the overall pattern in the approximately 40 patients described in the literature. The main symptoms are fluctuating higher cognitive functions and cranial nerve dysfunction, with fairly rapid clinical onset of symptoms. Most cases of central neurologic involvement with mycosis fungoides emerge within a setting of advanced disease. In patients with newly diagnosed mycosis fungoides, the greatest risk of developing neurologic involvement is within the first several years after diagnosis and is associated with the initial stage of disease. Patients with two or more of the T3-4, N3, M1, and B1 classification factors have a one in six chance of developing central neurologic involvement, while there is about a one in a hundred chance for the corresponding control group. Neurologic involvement with mycosis fungoides is indeed rare, but it is associated with a more advanced stage at diagnosis and with other visceral disease that can precede it. Although the role of low-dose prophylactic cranial radiation is uncertain, overt neurologic involvement requires urgent palliative treatment.

Detection of a Peripheral Blood T Cell Clone is an Independent Prognostic Marker in Mycosis Fungoides

T cell receptor gene analysis is a sensitive method for assessment of peripheral blood involvement in mycosis fungoides. This study uses polymerase chain reaction/single-strand conformational polymorphism (PCR/SSCP) analysis of the T cell receptor gamma gene and relates the results to skin stage and outcome in mycosis fungoides. Seventy-five peripheral blood samples from 66 patients were obtained from 1990 onwards and subjected to PCR/SSCP. Both Southern blot analysis and PCR/SSCP analysis were performed on 63 samples from 56 patients. Fourteen patients had T1 disease (12 IA, two IIA), 20 T2 (14 IB, five IIA, one IVA), 29 T3 (24 IIB, two IVA, three IVB, two patients tested at both T2 and T3), and five T4 (all III). The percentage of positive samples was higher with PCR/SSCP than with Southern blot analysis (29 of 63 vs eight of 63 samples, p < 0.001), and the percentage of positive samples increased with each stage (21% at T1, 35% at T2, 58% at T3, and 71% at T4). Proportional hazards analysis corrected for age, skin, and lymph node stage showed that the presence of a peripheral blood clone is associated with a worse outcome (p = 0.03, CI 1.1-6.03). These results indicate that the presence of a peripheral blood clone is an independent prognostic variable in patients with mycosis fungoides after correcting for age, skin, and lymph node stage, and that peripheral blood involvement is present in a large proportion of patients with early stage mycosis fungoides. polymerase chain reaction/single-strand conformational polymorphism/T cell receptor gene rearrangement. J Invest Dermatol 114:117-121, 2000

Ocular involvement in mycosis fungoides.

A case of mycosis fungoides with bilateral intraocular involvement is reported. The diagnosis was established with the aid of a vitreous biopsy. Intraocular involvement, though rare, may be an early sign of extracutaneous disease.

Expression of c-myc in Cutaneous Lymphomas and Pseudolymphomas

The expression of the proto-oncogene c-myc was studied in tumorous skin lesions of (cutaneous) lymphoproliferative diseases (3 cases of pseudolymphoma, 8 cases of non-Hodgkin lymphoma and 1 case of lymph node involvement in mycosis fungoides) in a total of 12 patients. c-myc mRNA levels were quantified by Northern blot analysis followed by densitometric evaluation of the specific bands. Higher levels of c-myc mRNA expression were observed in lymphomas as compared with pseudolymphomas (p greater than 0.05). No significant differences in c-myc mRNA values were detected between B and T cell pseudolymphomas. Our results suggest that c-myc mRNA overexpression is associated with malignant lymphomas of the skin. We conclude that the measurement of c-myc mRNA levels may contribute to further characterize cutaneous lymphoproliferative diseases.

Staging lymphography with respect to lymph node histology, treatment, and follow-up in patients with mycosis fungoides.

Extracutaneous involvement in mycosis fungoides (MF) is associated with a poor prognosis. Therefore, a pretreatment staging procedure is used to determine the extent of the disease. As part of the staging procedure lymphography was performed in 36 patients with MF. The radiographic findings and the correlation of these findings with the histopathologic changes in lymph nodes and the clinical course are described. Lymphography in MF shows a variety of abnormalities. However, these abnormalities correlate in only 61% of the patients with the extent and the clinical course of the disease. It is concluded that lymphography is not a useful clinical tool in the staging of MF.

Dermatopathic lymphadenopathy and lymph node involvement in mycosis fungoides.

Lymph node involvement in mycosis fungoides (MF) is associated with a poor prognosis, Histologically, in most cases of clinical lymphadenopathy the excised lymph node shows dermatopathic lymphadenopathy (DL). The diagnosis of MF involvement can readily be made when the lymph node tissue has partly or wholly been replaced by atypical lymphoreticular tissue. Early involvement of a dermatopathic lymph node by MF may be difficult to diagnose. A histologic study was performed on 30 lymph nodes from 24 patients with MF. Most of these lymph nodes had been excised as part of the staging procedure. The maximal follow-up period was five years. A classification of lymph node involvement into four categories is suggested and correlations with clinical courses and results of DNA cytophotometry of lymph node imprints are shown. Lymph nodes showing the histologic picture of DL can be divided into two groups: a group with MF involvement (category I) and a group with MF involvement (category II). The latter group is considered to represent early involvement of lymph nodes by MF. Partial or complete replacement of lymph node tissue by atypical lymphoreticular tissue corresponds with cagegories III and IV, respectively.

DNA-Cytophotometry of Lympho Node Imprints from Patients with Mycosis Fungoides

To obtain objective criteria for early diagnosis of lymph node involvement in patients with mycosis fundoides, Feulgen DNA-cytophotometry was carried out in lymph node imprints from patients with mycosis fungoides. The lymph nodes of 3 patients with lymph nodes, showing partial or total replacement by atypical lymphoreticular tissue histologically, showed a polyploid and aneuploid DNA distribution. Eleven out of 22 patients with dermatopathic lymphadenopathy both with or without early involvement histologically had an abnormal DNA histogram with hypertetraploid DNA values. Four of these 11 died, 5 had a partial remission in response to therapy and 2 had sustained remission during the follow-up period of 5 yr. The other 11 patients had a normal DNA distribution. Of these 11, one died and 10 achieved sustained remission after therapy. There is a good correlation between the DNA-cytophotometric results and histology of the lymph nodes. On the basis of these results DNA-cytophotometry may be considered an additional and objective aid in the diagnosis of lymph node involvement in mycosis fungoides.

Bone marrow involvement in mycosis fungoides demonstrated by needle biopsy.

A bone marrow needle biopsy was performed in 19 patients with mycosis fungoides (MF). Two patients, one previously classified as stage 4 and the other with diffuse erythroderma had pathological bone marrow findings. Seventeen patients showed no evidence of bone marrow involvement, 10 of these were in the plaque stage. Bone marrow biopsy can be of value in assessing the stage of the disease.

Adriamycin therapy in advanced mycosis fungoides.

Thirteen patients with advanced mycosis fungoides received induction therapy with Adriamycin, 60/m2 I.V. repeated at 21-day intervals. Ten patients had extensive skin tumors; all patients had lymph node enlargement with mycosis fungoides involvement in eight; four patients had biopsy-proven visceral involvement. Only two patients had received no prior therapy. The overall response rate with Adriamycin therapy was 85% with three patients (23%) achieving a biopsy-proven complete remission and five patients (39%) partial remissions. The median number of courses to maximum response was two (range two to four). The principle toxicity was myelosuppression, but this was not severe and the entire group received more than 90% of the intended doses of Adriamycin. One patient developed probable Adriamycin cariotoxicity. Maintenance therapy for patients achieving a remission was methotrexate 15 mg/m2 I.M. twice weekly and cyclophosphamide 750 mg/m2 I.V. every 21 days. The median duration of complete remission was 32+ weeks (range 16+-40+ weeks) while the median duration of partial remission was 18 weeks (range 8-111+ weeks). Adriamycin has proven to be an effective induction agent in the treatment of advanced mycosis fungoides and its incorporation into combination chemotherapy regimens is warranted.

Looking at the Eye for Clues to Systemic Disease

There are many systemic diseases in which eye signs detectable without an ophthalmoscope may be present. Examples are congenital glaucoma in neurofibromatosis, corneal involvement in mycosis fungoides, chloroma in leukemia, and uveitis and glaucoma in herpes zoster.