Clinical Features of Folliculotrophic Mycosis Fungoides

INTRODUCTION AND OBJECTIVES:

Folliculotrophic mycosis fungoides (FMF) is an uncommon and distinct variant of mycosis fungoides (MF) that is often difficult to diagnose and treat. To identify prognostic factors, we analyzed the prognostic relevance of clinical, and histologic features in FMF patients.  

MATERIALS AND METHODS:

We queried the MD Anderson Cancer Center cutaneous T-cell lymphoma database for patients with a diagnosis of folliculotrophic mycosis fungoides (FMF). The patients’ charts were reviewed and patients were included if they displayed a biopsy showing histologic and immunohistochemical features consistent with FMF. Clinical and histopathologic features, prognostic features including overall survival (OS), progression free survival (PFS), and disease free survival (DFS), and treatment options were described in 114 patients with biopsy proven F-MF with and without large cell transformation (LCT). Survival outcomes were assessed using the Kaplan-Meier method and Cox proportional hazards regression.

RESULTS

We evaluated 114 patients (54% male, 46% female) 72% were Caucasian with median age at diagnosis of 56 yrs (range 22-86 yrs). Median overall survival (OS) and disease free survival (DFS) was not reached but median time to progression was 7.6 years (95% CI).  Histologic LCT in skin or nodes occurred in 24 patients (21%), including 12 within a year of initial diagnosis of FMF.  Median survival for patients diagnosed with large cell transformation (LCT) at time of diagnosis of FMF was only 2.4 yrs (0.4, 6.3; 95% CI).  Median time to progression was 1.5 yrs (0.4, 6.3: years; 95% CI and median PFS for patients diagnosed with LCT diagnosed at 1-year was 5.6 (1.9, 6.3) years. Patients > 65 years were about 4.5 times more likely to die than <65 (Table 1). Female patients had a reduced risk of death compared to male patients (p=0.05).

In Univariate analysis: Increased risk of death was associated with lymph node stage (2x), Stage IV vs Stage IA, increased white cell count (WBC) (5x), visceral involvement (M0) (20 x), erythroderma (T4)(4.7 x), involvement on the chest (3.6 x), pruritus (7.8x), and increased lactic dehydrogenase ( 2x). Patients with FMF on the chest were 3.6 times more likely to die. Patients with pruritus were about 7.8 times more likely to die. In multivariate analysis: Increased risk of death was associated with LCT at time of diagnosis (13X), increased WBC (8X).

The most frequent skin directed therapies were topical steroids (85%), nitrogen mustard (45%), and total body skin electron beam (TBSEB) 32%.  The most common systemic therapies were bexarotene (46%), other retinoids (34%) and brentuximab vedotin (7.0%). Patients with FMF on the head/face were more likely to respond to oral bexarotene. Patients receiving local radiation and TBSEB had the highest response rates 79% (23/29) and 68% (25/37), followed by extracorporeal photopheresis (ECP) 56% (5/9), topical steroids 48% (47/97), retinoids 44% (14/32), oral bexarotene 36% (19/53), interferon 31% (4/13), and methotrexate 20% (3/15).

Table 1- Univariate analysis of OS, PFS and DSS for FMF

Univariate Analysis
	OS		PFS		DSS
Factors	HR [95% CI]	p	HR [95% CI]	p	HR [95% CI]		P
Age
>65	4.52 [2.06, 9.88 ]	0.0002	2.20 [1.20, 4.02]	0.01	2.96[0.89, 9.78]		0.07
LCT
<1 year	7.17 [2.62,19.67]	0.0001	4.44 [1.89, 10.4]	0.0006	3.54 [0.40, 31.63]		0.2581
LDH
>618	1.002 [1.001, 1.003]	0.0056	1.00 [1.000,1.002]	0.0076	1.00 [1.00, 1.00]		0.0145
Symptoms
Erythroderma	4.73 [1.58, 14.7 ]	0.0054	3.10 [1.21, 7.96]	0.018	1.87 [1.33, 31.87]		0.020
FMF on Chest	3.6 [1.35, 9.59 ]	0.014	3.83 [1.82 , 8.04 ]	0.0004	1.41 [0.882, 19.1]		0.07
Pruritus	7.85 [1.06, 58.0 ]	.043	5.069 [1.55, 16.5]	0.007	16.49 [0.00, NE]		0.99

CONCLUSIONS

Folliculotropic mycosis fungoides is an important entity requiring proper diagnosis and early treatment with radiation, ECP, topical steroids and retinoids.  FMF is clinically more aggressive than classic MF and was associated with large cell transformation in 21% of FMF patients. Prospective studies on the clinical course and treatment responsiveness of FMF are planned.