Patch Stage Mycosis Fungoides Research Articles

MicroRNA Expression Profile in Mycosis Fungoides – Preliminary Findings

Dear Editor, Mycosis Fungoides (MF) is the commonest cutaneous lymphoma, comprising about 12% of all T-cell lymphomas in India.[1] MF presents as patches, plaques or tumors. While the diagnosis of tumor stage MF is easy, lesions of patch and plaque stages pose problems in diagnosis.[2] There is a clinicopathologic overlap with several inflammatory conditions. Currently, there is no single diagnostic standard for early MF. It rests on a combination of clinical findings, histopathology, immunohistochemistry and T-cell receptor clonality testing.[3] miRNAs(miR) have great potential as biomarkers as they are robust, tissue-specific and can be obtained from both blood and tissues. Their value as diagnostic markers have been shown in several cancer types but is still nascent in MF.[4] We attempted to explore the role of miRs in patch and plaque stage MF in Indian patients. We selected 24 MF samples whose diagnosis was established based on clinical features, histopathology and follow up. We chose a set of 7miRs namely miR 203, miR205, miR223, miR155, miR 93, miR 92a, miR 21 along with two controls RNU48 and RUN44. The first three miRs have a tumor suppressor function, while the rest serve as OncomiRs. RNU44, 48 served as controls. Primer sequences designed using Primer3Plus software and then validated on Ensemble & NCBI Blast. After deparaffinisation and overnight incubation with proteinase K, RNA was extracted using RNAwiz and estimated by Ribogreen fluorimetry, the yield ranged from 5.06 to 49.6 ng. Real time PCR was done on the 26 samples on LightCycler 480 (Roche). Pre-incubation and initial denaturation of the template was at - 95°C for 10 min and amplification was done for 45 cycles at 95°C for 15 sec and 60°C for 1 min and Ct values were obtained. There were 24 samples from 21 patients. Their age ranged from 24-83 years and were predominantly men (14:7). There were 8 patch stage MF, 9 plaque stage and 7 were recurrent MF. There was no significant difference in the expression of any of the 7 miRs between the patch and plaque stages (p-values ranged from 0.423-0.963). There was no difference between patch/plaque stages and recurrent lesions. (p-values ranged from 0.481-0.963). We compared the average Ct values of the 3 tumor suppressor miRs versus the 4 OncomiRs, to look for any difference between patch, plaque and recurrent lesions. There was no significant difference in these either. (p-value ranged from 0.877 to 1.484) A few studies have focussed on the differential expression of miRs in distinguishing MF from inflammatory diseases. van Kester et al studied 19 tumor stage MF and compared their miR expression patterns with 12 benign skin conditions.[5] They found that 49 miR were differentially expressed in the two groups and miR 93, which has an anti-apoptotic function, showed the highest discrimination.[5] Ralfkiaer et al showed that early MF displays a miR profile distinct from advanced T-cell lymphomas.[6] They were also able to demonstrate different profiles in patients with progressive vs. non-progressive disease. McGirt et al demonstrated that miR223, which targets TOX gene, needed for T-cell development is overexpressed in early MF and diminishes with progression to advanced disease.[7] There is only one study which has compared miR profiles in patch vs. plaque stages of MF. Sorensen et al found 11 miRNAs were overexpressed in plaques as compared to patches, most significantly miR-142, miR-21 and miR-22.[8] We did not find any difference in miR (including miR21) expression between patch and plaque stages or in patients who had recurrences. Variation in results could be due to the methodology used (whole tissue vs. microarray), quantity and quality of RNA and density of the infiltrate.[8] Nevertheless, it seems that although clinically distinct, patch and plaque stage MF are more similar biologically. We will expand the scope to compare miR expression profiles of MF with various inflammatory skin diseases in the next part of our ongoing study. To summarise, miR expression does not appear to be useful in distinguishing patch vs. plaque stage MF. Our findings need to be validated in larger samples in Indian patients. Financial support and sponsorship Rajiv Gandhi University of Health Sciences, Bangalore for funding the project Conflicts of interest There are no conflicts of interest.

Does CADM1 Immunohistochemistry Distinguish Mycosis Fungoides from its Closest Mimickers?

BackgroundImmunohistochemistry (IHC) sometimes fails to distinguish clinically ambiguous cases of evolving patch‐stage mycosis fungoides (MF) from relatively common, non‐neoplastic inflammatory skin diseases (ISD), particularly spongiotic dermatitis (SD), psoriasis (PSO), and pityriasis lichenoides (PL). CADM1 (cell adhesion molecule 1) is a tumor suppressor gene implicated in the pathogeneses of solid skin tumors, visceral malignancies, and peripheral T‐cell lymphomas. Recent data suggest that CADM1 IHC expression could help distinguish early‐stage MF from ISD.DesignThis pilot study sought to determine whether CADM1 IHC distinguishes MF from ISD in clinically‐annotated cases from our archives. MF (n=14), PL (n=10), PSO (n=10), and SD (n=10) were stained with CADM1. Using appropriate controls and antibody optimization, two pathologists established consensus scores in each case for percentage of lymphocytes staining with CADM1 and CADM1 staining intensity. The localization of CADM1‐positive cells (epidermis including junction and dermis) was also noted.ResultsThere were no differences in CADM1 expression pattern or intensity between groups. All cases showed moderate to strong nuclear CADM1 expression in ≥75% of lymphocytes in both the dermis and epidermis. Some intraepidermal lymphocyte nuclei were challenging to detect on CADM1‐stained slides given uniform moderate‐intensity staining of background keratinocyte nuclei.ConclusionThe challenge of distinguishing evolving patch‐stage MF from ISD facilitates demand for novel and readily available diagnostic tests. Although recent data have suggested that differential expression of CADM1 distinguishes MF from ISD, there was no difference in lymphocyte CADM1 expression and distribution between any of the groups included in our pilot study. Furthermore, evaluation of CADM1 expression in intraepidermal lymphocytes was challenging given background keratinocyte expression.

Dermoscopic spectrum of mycosis fungoides: a retrospective observational study by the International Dermoscopy Society.

The dermoscopic features of classic patch stage mycosis fungoides (MF) have been described, but data on plaque and tumoral stage as well as rarer MF subtypes is limited. To evaluate dermoscopic morphology and dermoscopic-pathological correlations of classic MF stages and investigate dermoscopic features of MF variants. Patients with histopathologically confirmed lesions of classic MF (patch, plaque and tumoral stage) or folliculotropic, erythrodermic and poikilodermatous MF were included. Standardized evaluation of dermoscopic pictures of the included MF variants and comparative analysis and dermoscopic-pathological correlation assessment of different stages of classic MF were performed. A total of 118 instances were included (75 classic MF, 26 folliculotropic MF, 9 erythrodermic MF and 8 poikilodermatous MF). Linear/linear-curved vessels and white scales in the skin furrows were significantly associated with patch-stage MF, while clustered dotted vessels were related to plaque-stage MF and peripheral linear vessels with branches, ulceration and red globules separated by white lines to tumour-stage MF. Moreover, patchy white scales were significantly more common in patches and plaques compared to tumours, whereas focal bright white structureless areas were related to plaque and tumoral stage. Vessels histopathologically corresponded to dilated vascular structures in the dermis, orange structureless areas to either dermal hemosiderin (patch/plaque stage) or dense cellular infiltration (tumours), bright white lines/structureless areas to dermal fibrosis and ulceration to loss of epidermis. The main dermoscopic findings of folliculotropic MF were lack of hairs, dilated follicles and follicular plugs, while erythrodermic MF was mainly characterized by linear/dotted vessels, patchy white scales and focal orange structureless areas and poikilodermatous MF by focal white and brown structureless areas, white patchy scales and brown reticular lines. Dermoscopy may allow a more precise characterization of classic MF and reveal clues suggestive of the main MF variants.

P03 Not everything is lupus

P03 Not everything is lupus

Early morphea simulating patch-stage mycosis fungoides in two cases.

Morphea is a skin disorder characterized by thickening of dermis and subcutaneous tissues and loss of adnexal structures. In the early inflammatory stage of morphea, diagnostic histological findings are absent and this may lead to confusion with other inflammatory dermatoses such as mycosis fungoides (MF). We report two cases of early stage morphea mimicking patchstage of MF. Histopathologic examination of biopsies obtained early in the disease course revealed lymphocytic epidermotropism arranged in small pautrier-like collections as well as linear arrangements in dermal- epidermal junction. Additional biopsies were performed which revealed replacement of subcutaneous fat with closely packed thick collagen bundles under eccrine glands. This report points toward the fact that early stage morphea can simulate MF. Therefore additional evaluation is sometimes required for definite diagnosis.

Interleukin-12 immunohistochemistry as a diagnostic tool for patch-stage mycosis fungoides

Interleukin-12 immunohistochemistry as a diagnostic tool for patch-stage mycosis fungoides

Interstitial Mycosis Fungoides With Lichen Sclerosus–Like Clinical and Histopathological Features

Mycosis fungoides (MF) simulates a variety of dermatologic disorders histopathologically and clinically, well deserving the designation of a great mimicker. Interstitial MF is a rare, but well-recognized histopathological variant resembling the interstitial form of granuloma annulare or the inflammatory phase of morphea. From a clinical standpoint, MF can have a wide array of manifestations, including an anecdotal presentation with lesions clinically suggestive of lichen sclerosus (LS). We herein report a 25-year-old man with a history of patch-stage MF who later developed widespread LS-like lesions histopathologically consistent with interstitial MF. In some biopsies, additional features resembling LS were discerned. We think that our case might represent a unique variant of interstitial MF presenting with LS-like lesions. The diagnostic challenge arising from this uncommon presentation is discussed together with review of the literature.

‘Could it be mycosis fungoides?’: an approach to diagnosing patch stage mycosis fungoides

Mycosis fungoides (MF) is the most common primary cutaneous T cell lymphoma, which is characterised in its early stages by epidermotropism of small to medium-sized T lymphocytes with cerebriform nuclei. Originally described by Alibert in 1806, MF is classically a disease of adults, although children and adolescents can be affected, and it typically has a protracted, indolent course. Routine dermatopathology practice involves many biopsies submitted with a clinical query regarding the possibility of MF. These are not always straightforward, as the histological features can be variable and are not always readily distinguishable from several other clinical differential diagnoses. Whilst modern molecular testing modalities can assist, even these do not always enable a definitive diagnosis of MF in its early stages. We have reviewed the histopathological features of early MF and currently recognised subtypes and the role of immunohistochemistry and emerging molecular techniques in the diagnosis of this condition. We also outline our approach to a biopsy where the question of ‘Could it be MF?’ has been proposed.

Erythrodermic mycosis fungoides and Sézary syndrome treated with extracorporeal photopheresis as part of a multimodality regimen: A single-centre experience.

Extracorporeal photopheresis (ECP) is recommended for the erythrodermic mycosis fungoides (MF) and Sezary syndrome (SS) alone or in combination with other therapies. The possibility of a differential response in the blood and skin has hardly been addressed in the literature. To evaluate the clinical response rate of patients with erythrodermic MF and SS to ECP as part of a multimodality approach and to compare the kinetics of the blood and skin responses in the presence of leukaemic involvement. Twenty patients were treated with ECP and other modalities at a tertiary medical centre in 2003-2013. Ten patients had SS, 1 CD8-positive patch-stage MF with leukaemic involvement and nine erythrodermic MF. Clinical and outcome data were collected retrospectively from the medical files. Response was evaluated overall and for blood and skin separately. Adjunctive therapies were interferon-α, narrow-band ultraviolet B, psoralen and ultraviolet A, isotretinoin, acitretin, methotrexate, prednisone, topical nitrogen mustard and total skin or localized hands/feet electron beam radiotherapy. Overall response was documented in 13 patients (65%)--complete 30%, partial 35%--and maintained for >2 years in 38.5%. In patients with leukaemic involvement (n = 11), the blood response occurred earlier than skin response (P = 0.008) and was maintained longer (P = 0.03). In three of the patients with a complete blood response, the skin response was partial (n = 2) or absent (n = 1). Extracorporeal photopheresis as part of a multimodality approach yields a high durable clinical response in patients with erythrodremic MF and SS. The kinetics of the response differ between the blood and skin. The blood response occurs earlier and lasts longer; it does not necessarily predict the clinical skin response. Further studies are needed to determine if there is a survival advantage to a blood response in the absence of a skin response.

Foxp3+ T-lymphocytes in the pathogenesis of mycosis fungoides

The pathogenesis of mycosis fungoides (MF) is not fully understood, nevertheless it is believed that the microenvironment of the tumor cells could influence the development of malignant lymphocytes. T-regulatory cells are a specialized subpopulation of T-lymphocytes, which can have an immunosuppressive effect and thus affect the immune response. Goal. The study population of regulatory T-cells in the skin of patients with mycosis fungoides and llaque parapsoriasis. Materials and methods. The content of Foxp3+ and CD3+ cells by immunohistochemical studies of skin biopsy specimens from patients with patch stage mycosis fungoides (10 patients) and plaque parapsoriasis (10 patients). The control group consisted of 16 healthy individuals. Results. Relative expression area Foxp3+ cells in patients with mycosis fungoides patch stage (0.44%) 2.6 times greater than in patients with plaque parapsoriasis (0,14%; p < 0,05). Part the Foxp3+ cells of the total number of T lymphocytes in patients with patch stage mycosis fungoides (5.9%) and plaque parapsoriasis (4.7%) were not significantly different (p > 0,05). Conclusion. In the initial stage of patients with mycosis fungoides determined a statistically significant predominance of the absolute number of T-regulatory cells in the epidermis and in the dermis. Part T-regulatory cells from all of T-lymphocytes in patients with skin patch stage mycosis fungoides and plaque parapsoriasis not statistically significantly different.

Expression of helper T cell master regulators in inflammatory dermatoses and primary cutaneous T-cell lymphomas: Diagnostic implications

Mycosis fungoides (MF) is a neoplasm of skin-homing CD4(+) helper T (TH) lymphocytes with dysregulation of TH1 and TH2 immunity. Diagnosis of MF is challenging, as there is significant morphologic overlap with other dermatologic entities. We investigated diagnostic utility of TH1- and TH2-specific markers, T-bet, and GATA-3, respectively, in MF and its reactive and neoplastic mimics. Immunohistochemical staining for CD3/T-bet and CD3/GATA-3 was performed on inflammatory dermatoses (n = 56), MF (n = 37), Sezary syndrome (SS; n = 8), and cutaneous anaplastic large cell lymphoma (C-ALCL; n = 14). Inflammatory dermatoses showed epidermal T cells predominantly expressing GATA-3, except psoriasis, which exhibited a mixed GATA-3/T-bet staining. In contrast, neoplastic T cells in patch stage MF showed markedly increased T-bet positivity with minimal GATA-3 expression. Plaque stage MF had amixed T-bet/GATA-3 phenotype, whereas tumor stage MF and SS exhibited diffuse GATA-3 expression. C-ALCL lacked significant staining for both markers. Sample size was relatively small. A predominance of T-bet(+) T cells in the epidermis support patch stage MF over dermatitis. A predominance of GATA-3(+) Tcells in the dermis support CD30(+) MF with large cell transformation over C-ALCL. These stains donotallow distinction between dermatitis and cutaneous infiltrates of SS.

Transforming growth factor-β1 gene polymorphism in mycosis fungoides.

Dysregulation in transforming growth factor (TGF)-β1 signalling pathways has been linked to cancer. To study the association between single nucleotide polymorphisms (SNPs) of the TGF-β1 gene and mycosis fungoides (MF). Using restriction fragment length polymorphism analysis, SNPs in the TGF-β1 gene were studied in 55 patients with MF of different stages and in 100 apparently healthy controls. A significant difference was found between patients and controls in distribution of the different TGF-β1 genotypes, with mutant forms (T/C, T/T) encountered significantly more often in patients with MF (P<0.001). The heterozygous genotype (T/C) was significantly associated with patch stage MF, whereas the homozygous genotype (T/T) was significantly associated with tumour stage (stage IIb) MF (P=0.001), although this study included only a small number of these patients. Mutant TGF-β1 genotypes are significantly associated with MF in Egyptian patients, with the homozygous genotype (T/T) having a stronger association with tumour stage (stage IIb).

Cutaneous composite lymphoma in the setting of chronic patch-stage mycosis fungoides

Cutaneous composite lymphoma in the setting of chronic patch-stage mycosis fungoides

Mycosis Fungoides With Large Cell Transformation and T Follicular Helper Phenotype

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma and is usually characterized by a T-helper phenotype of neoplastic cells. Several clinical, histopathologic, and phenotypic variants of the disease have been described. We report on a case of MF in tumor stage with neoplastic cells expressing a T-follicular helper phenotype, characterized by positivity for PD-1, Bcl-6, and CXCL-13. Retrospective analysis of the first diagnostic biopsy of patch stage MF revealed a similar phenotype. This review addresses the clinical, histopathologic, phenotypic, differential diagnostic, and prognostic features of typical and of less conventional cases of MF.

Early stage mycosis fungoides with focal CD30-positive large cell transformation

Mycosis fungoides (MF) is typically an indolent disease except when large cell transformation (LCT) occurs. The incidence of LCT has been reported to range from 6% to 23% under the criterion of the presence of more than 25% of large cells in a biopsy of typical MF lesions. LCT is more common in advanced-stage MF, but very rarely found in its early stage. Herein, we present a 45-year-old woman with patch stage MF (Stage IB) who developed a papule within one patch, which revealed large cell transformation with expression of CD30 immunostaining on histopathology. The patient then received phototherapy with narrow-band UVB. The skin lesions regressed quickly and no new skin lesions had been noted during the 6-month follow-up. Intense monitoring for recurrence and extracutaneous involvement is still recommended. In this article, we also review the published articles of mycosis fungoides with CD 30-positive large cell transformation and analyze the clinicopathological and prognostic features.

Eosinophils in Mycosis Fungoides

Early diagnosis of mycosis fungoides (MF) is one of the most challenging problems in dermatopathology, as the histopathologic features of inflammatory dermatoses and MF may show significant overlap. One criterion used to distinguish early MF (patch stage) from dermatitis, which may be currently underutilized, is the presence of eosinophils. A search was performed for cases with a preoperative diagnosis of MF, cutaneous T-cell lymphoma, or dermatitis, which included 29 cases "diagnostic" for MF, 25 cases "suspicious" for MF, and 55 cases of spongiotic dermatitis. We examined tissue sections blinded to diagnosis to obtain an exact eosinophil count. Twenty-nine cases were diagnostic for MF (12 patch, 9 plaque, and 8 tumor stage). The average eosinophil count for cases diagnostic for patch stage MF was 1 eosinophil in 10 (0.11) sections examined. For plaque MF, there was 1 eosinophil in 5 (0.24) sections examined. All tumor stage MF cases showed abundant eosinophils within each section. Twenty-five cases were suspicious for MF (15 patches, 9 plaques, and 1 folliculotropic). The average eosinophil count for the patch lesions was 1 eosinophil in 4 (0.25) sections examined and 2 eosinophils per section for plaque lesions. Forty-five of 55 cases of spongiotic dermatitis had at least scattered eosinophils (>3) in each section. Twenty-three (47%) had eosinophils around most postcapillary venules. Only 3 of 45 patients (6.6%) with biopsies diagnostic or suspicious for patch or plaque stage MF showed >3 eosinophils per tissue section, whereas 45 of 55 (81.8%) biopsies of spongiotic dermatitis had >3. The presence of eosinophils (>3 per tissue section) is statistically significant in differentiating cases diagnostic or suspicious for patch or plaque stage MF from dermatitis (P < 0.0001). Our data indicate that eosinophils are uncommon in cases of patch and plaque MF. When a pathologist is faced with evaluating a biopsy that lacks some of the criteria used to make the diagnosis of patch stage MF, yet demonstrates >3 eosinophils per tissue section, dermatitis is the likely diagnosis. However, in cases where fewer than 3 eosinophils are present in sections, patch stage MF cannot be excluded.

Coexistence of Patch Stage Mycosis Fungoides and Interstitial Granuloma Annulare in the Same Patient

Several clinical and histopathologic variants of mycosis fungoides (MF) have been well described, including the often elusive interstitial MF. Differentiation from other inflammatory disorders, such as interstitial granuloma annulare (GA) and inflammatory morphea, may be extremely difficult. We report a case of MF and GA coexisting in a 54-year-old woman who initially presented to clinic in 2000 with slightly scaly patches on the trunk and extremities, histopathologically diagnostic of MF. A second biopsy taken a few months later revealed an interstitial infiltrate that was initially interpreted as interstitial MF. Over the following 10 years, additional biopsies revealed features of conventional MF. In 2009, a new biopsy showed unequivocal features of interstitial GA. Reevaluation of the original biopsy, diagnostic of "interstitial MF," revealed that this, too, could be better classified as interstitial GA than interstitial MF. Our case illustrates that MF and interstitial GA may coexist simultaneously, thus representing a pitfall in the histopathologic diagnosis of MF. Given the similarities in clinicopathologic presentation, dermatologists and dermatopathologists should be cautious not to inadvertently misinterpret GA as interstitial MF.

The Histological Spectrum of Early Mycosis Fungoides: A Study of 58 Saudi Arab patients

The histopathological diagnosis of Mycosis Fungoides (MF) is challenging in its early stages and can easily be confused with inflammatory dermatoses. This study aims to; (i) assess the frequency and significance of different histopathological parameters in early MF, seen in Saudi patients, and (ii) to study the utility of these parameters in differentiating between early MF and inflammatory dermatoses. This is a five years study of 66 skin biopsies generated from 58 patients with clinically suspicious MF lesions or early patch stage MF. These cases were retrieved from the archives of the Department of Pathology, King Khalid University Hospital, Riyadh from the year 2002 to 2006. Histological criteria were assessed and graded semi-quantitatively on a four-point scale by a dermatopathologist and two pathologists independently. The histological parameters suggesting the diagnosis in early stages MF include epidermotropism, dermal fibrosis, Pautrier's micro abscesses, Basal alignment of neoplastic lymphocytes, hyperconvoluted dermal and epidermal lymphocytes and grandiosity sign (size of lymphocytes becoming larger as they migrate towards granular layer of epidermis). These parameters on univariate analysis achieved statistical significance (p<0.05) in differentiating MF from non-MF cases. In addition, hyperconvoluted dermal and epidermal lymphocytes proved to be highly reliable with high specificity and sensitivity. The histopathological diagnosis of early MF lesions and their discrimination from inflammatory simulators can be achieved by carefully observing the hyperconvoluted dermal and epidermal lymphocytes along with the constellation of the other parameters.

Origin Use of CD4, CD8, and CD1a Immunostains in Distinguishing Mycosis Fungoides from its Inflammatory Mimics: A Pilot Study

Patch-stage/early mycosis fungoides (MF) is difficult to differentiate from benign dermatoses, despite several robust histologic criteria. Most studies include advanced lesions and data about early disease is limited.Objectives:(1) To compare the CD4:CD8 ratio in patch-stage MF versus inflammatory mimics. (2) To study patterns of CD1a expression in the epidermis and dermis in the two groups.Materials and Methods:Twenty cases each of early MF and inflammatory dermatoses were selected. The diagnoses were established after clinicopathologic correlation, repeat biopsies, and follow-up. The inflammatory group included pityriasis lichenoides chronica, actinic reticuloid, lichenoid purpura, and various psoriasiform dermatoses. Immunohistochemistry was done for CD4, CD8, and CD1a. Epidermal CD4, CD8 cells were quantified and CD1a was graded semi-quantitatively in the epidermis and dermis.Results:The average CD4:CD8 ratio was 4.2 in MF (range: 1-16.8), and 0.9 in inflammatory diseases (range: 0.43-5), which was statistically significant (P < 0.0001). None of the MF cases had a ratio <1. Four cases of pityriasis lichenoides chronica had a ratio >1. CD1a cells had a continuous or confluent epidermal pattern in almost all cases of MF, while they occurred as small or large groups in the dermis. In inflammatory dermatoses, there were either isolated or scattered CD1a+ cells in both epidermis and dermis.Conclusions:Elevated CD4:CD8 ratio favors MF. But there is an overlap in the lower range with pityriasis lichenoides chronica. These cases require good clinicopathologic correlation and follow-up. Patterns of CD1a expression are more reliable. Immunostains buttress morphology and are a valuable addition.

A Case of ALK+ Anaplastic Large T Cell Lymphoma (ALCL) with Lymphomatous Meningitis

Abstract 5226 Background:Anaplastic large T cell lymphoma may present with indolent cutaneous T cell infiltration, progressing to more aggressive skin disease and systemic involvement. In adults lymphomatous meningitis is very rare complication. Case Report:A 62 year old Jamaican woman had been diagnosed with biopsy proven psoriasis when 42 years of age. Ustekinumab had been initiated without effect two months prior to her presentation to us. A new cutaneous nodule on her left neck was then found, shave biopsy of which revealed psoriasiform dermatitis with epidermotropism, suspicious for early patch stage mycosis fungoides. The lesion was CD30+, suggestive of ALCL and was positive for ALK. Positron emission tomography revealed an SUV of 6.0 in the neck mass, but lymph nodes in all regions had an SUV of <2.3. Axillary lymph node biopsy, bone marrow biopsy and flow cytometry were negative. Local electron beam radiation was administered to the left supraclavicular space with complete resolution of the cutaneous nodule. About 2 months following completion of radiation therapy she noted anorexia, 30 lb weight loss, night sweats and left hip pain. Physical examination revealed a sick woman, with whole body scaling red-brown macules and plaques. CBC was normal except for Hb of 10 g/dl, platelets 453,000/dl. Hepatic and renal function studies were normal. ESR was 84 mm/hr, lactic dehydrogenase 670 IU (reference range 300–600 IU) and calcium 15.1 mg/dl. HTLV1, HIV, hepatitis panel and anti-nuclear antibody serologies were negative. Computer automated tomography of the pelvis demonstrated 6×2×8 cm soft tissue mass on the sacrum invading left sacro-iliac joint and ilium. Biopsy revealed ALCL, positive for CD43, CD2dim, CD7dim, CD30, and nuclear and cytoplasmic ALK1, while negative for CD43, 3, 4, 5, 8, 19,20, 34, 138, PAX5, AE1/AE3, Cam5, S100 and TdT. The mass was irradiated with alleviation of pain, but cutaneous nodules progressively appeared and continuous fever developed with negative blood cultures. There was increasing confusion, blurred vision and bilateral abducens paralysis. Magnetic resonance imaging of the head and spine revealed dural enhancement and multiple extra- and intercranial interosseous masses, one of which involved the posterior sella turcica. Cyclophosphamide, doxorubicin, vincristine and prednisone were initiated; lumbar puncture was refused. Within 2 days after treatment initiation the cutaneous nodules disappeared, fever subsided, the left abducens palsy resolved completely while the right improved. Conclusion:Our patient's long standing indolent skin disease abruptly progressed to cutaneous and systemic ALCL, with evidence of lymphomatous meningitis. The response of her abducens palsies and other CNS findings to systemic chemotherapy alone suggests that her meningeal involvement may have arisen from that of adjacent bones. Involvement of CNS in ALK positive systemic anaplastic large cell lymphoma is rare and reported in mainly pediatric cases. Disclosures:No relevant conflicts of interest to declare.