Case Reports in Dermatological Medicine

Case Reports in Dermatological Medicine / 2016 / Article

Case Report | Open Access

Volume 2016 |Article ID 5857935 | 7 pages | https://doi.org/10.1155/2016/5857935

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

Academic Editor: Alireza Firooz
Received13 Aug 2016
Revised26 Oct 2016
Accepted06 Nov 2016
Published15 Dec 2016

Abstract

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.

1. Introduction

One of the most common T-cell lymphomas is mycosis fungoides (MF). It is a malignant, insidious, cutaneous, extranodal non-Hodgkin’s lymphoma (NHL) [1]. MF encompasses about 4% of all lymphoma cases worldwide and has an incidence of 0.36 per 100,00 [2]. The MF disease process has a relatively predictable pattern: in three phases, erythematous or eczematous patches can become infiltrated plaques and cutaneous tumors [1]. Extracutaneous manifestations of MF can involve a wide array of sites, particularly lymph nodes [3].

Oral cavity involvement in MF is rare, found in less than 1% of patients. Interestingly, autopsy studies suggest up to 13% involvement [4]. This is thought to be a predictor of poor prognosis. Often, patients have advanced stage disease and the majority have expired shortly after presentation [58]. We present a case of oral MF and a review of the literature. Two additional patients with oral MF that presented to our hospital are presented in table form alongside the 45 patients with oral MF found in the literature (Table 2). Key observations are made from analysis of the patients.

2. Materials and Methods

We have expanded on our previous case series on oral MF (20) to include three new cases that were selected from the electronic medical records of The University of Texas MD Anderson Cancer Center (UTMDACC). The patients were treated at UTMDACC over periods from 2005 to present (Case  1), 2005 to 2008 (Case  2), and 2015 to present (Case  3).

3. Case Report

A 63-year-old white man (Case  1) presented in 2005 with exfoliative erythroderma. He stated that he was diagnosed with a rash localized to his right hand three years earlier. Over the course of one and a half years, his lesions spread widely. On presentation, he had 90% body surface area (BSA) involvement with a 3 : 1 ratio of plaque to patch. His skin exhibited indurated erythematous papular rash that was confluent over the upper and lower extremities with skip areas on the abdomen and relative sparing of the groin.

Flow cytometry revealed 30 × 109/L CD4 cells and 96% CD4+/CD26− cells. Biopsy of the tumor showed MF with large cell transformation.

The patient received numerous systemic treatments including (1) vorinostat 400 mg daily that improved his pruritus but was accompanied by intolerable side effect of diarrhea and overall lack of response in the skin, (2) forodesine with minor partial response, (3) combined modality with interferon-alpha plus bexarotene and extracorporeal photophoresis, (4) total body skin electron beam radiation that effectively cleared his skin temporarily, and (5) alemtuzumab with which he achieved durable near-complete remission.

After these treatments, roughly four years after initial presentation, the patient presented with a rapidly growing tumor on his tongue measuring 2.0 × 2.0 × 2.5 cm with a central cleft (Figure 1). His skin at that point had 12% BSA involvement of MF. His tongue biopsy showed a large protruding lesion, lined by squamous mucosa, nonulcerated, composed of a diffuse, dense lymphoid infiltrate that extended deep into underlying skeletal muscle of tongue (Figure 2(a)). On higher magnification, the neoplastic cells were large, with vesicular nuclei and prominent central nucleoli (Figure 2(b)). Approximately 2 atypical mitotic figures per high power field were identified. The large neoplastic cells were strongly and diffusely positive for CD3 (Figure 3(a)) CD4 and CD30 (Figure 3(b)). Approximately 90% of neoplastic cells expressed the proliferation marker Ki-67. Bone marrow was positive for atypical cells as well. Imaging revealed a 1.3 cm spiculated lesion in the left upper lobe, which was subsequently biopsied and found to be positive for lymphoma. His tumor responded to 22 Gy of electron beam radiation leaving behind a 3.0 × 1.5 cm erosion that eventually formed a scar. He was restarted on bexarotene and had an excellent response on the skin. He continues to be disease-free to the time of this writing.

4. Discussion

Lymphomatous lesions of the oropharynx in MF are becoming increasingly recognized in the literature. Presentation is heterogeneous, ranging from depressed ulcerations and red or white patches to exuberant outgrowth of tumors. This presents a diagnostic challenge to the uninitiated clinician. The differential diagnosis of various benign and malignant oral lesions is reviewed (Table 1).


DiseaseOral lesion descriptionDiagnostic clues

Malignancy/premalignancy
 Squamous cell papilloma Discrete exophytic papillary lesions (verruca): occur at any intraoral siteHistory of human immunodeficiency virus infection; association with cutaneous warts on fingers
 Squamous cell carcinoma Nonhealing ulcers, papules, or plaques: occur most frequently at the floor of the mouth and soft palateHistory of tobacco and alcohol consumption; mechanical trauma from ill-fitting dentures

Mesenchymal neoplasms and tumor-like lesions
 Fibrous and vascular overgrowths Discrete lesions of cheek or tongueHistory of chronic irritation, usually from some tooth-related cause or chronic cheek/tongue biting
 Pyogenic granuloma Exuberant overgrowths usually at the gingiva but can occur at any intraoral site May bleed spontaneously or following irritation due to extreme vascularity

Odontogenic tumors and cysts
 Ameloblastoma Oral swellings occurring on the mandible that typically produce multicystic appearance on radiograph Painless and slow growing; untreated, may reach substantial size
 Odontogenic cysts Oral swellings arising adjacent to teeth that usually produce a well-demarcated cyst on radiograph Painless and slow growing


AuthorAt onset of MFAt onset of oral lesionAt deathTime to death from onset of oral lesion (yr.)SexStageCutaneous involvementExtracutaneous involvementLymph node involvementMultiple sites of oral involvementPresence of GI involvementLesion typeLocation of oral lesion(s)
AgeAt onset of oral lesion

Laskaris526565.20.2FIIb++++Buccal mucosa, lips
Crane7073.5FIIaGingiva
Yao5457.859.11.3MIb++PatchGingiva, buccal mucosa
Brousset4750522FIb+TumorLingual margin
Vicente
 Case 1515959.50.5FIIb++PlaqueHard palate, mandibular gingiva
 Case  2727777.50.5FIIb+PlaqueHard palate
Kasha
 Case  1656667.21.2MIIb+PlaqueDorsal tongue
 Case  26280811MIIa++++PlaqueTongue, esophagus
Evans526566.21.2FIb++PlaqueDorsal tongue, Lateral tongue
Barnett396969.20.2MIIb++PlaquePalate, tongue, mucosa, gingiva, pharynx
Cohn5052.5MIIb++++PlaqueHard palate, buccal mucosa, tongue
Damm6868MIIb++Hard palate, soft palate, alveolar ridge
Whitbeck687272.60.6MIVb+++TumorHard palate and, later, tongue
Ellams525252.30.3FIb+TumorGingiva, buccal mucosa, palate
Reynolds6075.576.71.2FIb++PatchTongue, hard palate
Wright6061.562.71.2MIVb+++PatchHard palate, upper gingiva
Sirois
 Case  17175761MIVa++Gingiva, palate, tongue, lip, buccal mucosa, tonsil
 Case  24457581MIII+Tongue
 Case  34649501MIVa++Gingiva, tongue
 Case  47174751MIIb++Gingiva, palate
 Case  56266693FIIb++Gingiva, palate
 Case  65153563FIVa+Gingiva
 Case  76773818FIbGingiva
 Case  84351532MIII+Tongue
McBride6363.10.1FIIa+TumorDorsal tongue
Harman5757.60.6MIIb++Gingiva, palate
Cawley
 Case  17272742MIb++Hard/soft palate, tonsils
 Case  2656565.00.04MIIb++++TumorLabial commissure, tongue
Postorino et al.60MIIb++PlaqueMucosa
Corbett et al.FIIb++TumorSoft palate, throat
Wain et al.MIb++PlaqueSoft palate, tongue, lips
Wahie et al.6069MIa+Suprahyoid region, epiglottis
Viswanathan6969MIa++Tongue, soft palate
Luigetti et al.2738F++++PlaqueLip, mucosa, tongue, pharynx
Goldsmith et al.4464F+PlaqueHard palate
Le et al.3236MIIb+++TumorTonsil
Tillman et al.60M
Chua et al.8080.7MIb+TumorHard palate, gingiva, mucosa
Gomez
 Case  1354545.50.5FIIb++TumorTongue, uvula, oropharynx
 Case  26670FIb++Uvula, soft palate, tonsils
May
 Case  140FIa+TumorTongue
 Case  24444MTongue
Present report
 Case  16074MIVb++TumorTongue
 Case  2505555.70.7MIVb+++TumorPalate, uvula
 Case  33538MIVb++++UlcerTongue, palate

MF is classically divided into three progressive, often overlapping, stages: patch, plaque, and tumor. Clinically and histopathologically, patch stage MF is commonly misdiagnosed as psoriasis. Lesions appear erythematous and sometimes scaly usually responding to topical steroids, the mainstay treatment [9]. Microscopically, there is nonspecific inflammatory infiltrate. Atypical cells are not readily identified.

During the plaque and tumor stages, lesions present a much more characteristic histologic picture. There are a dense polymorphous infiltrate and characteristic epidermotropism. Malignant cells called Sezary cells may be seen in the peripheral blood and subsequently may spread to lymph nodes. Sezary cells can be identified in peripheral blood by flow cytometry immunophenotype [10]. Treatments are often directed systemically with medicines such as bexarotene, a vitamin A derivative. In our experience, lesions respond well to local electron beam radiation.

To our knowledge, there are 42 reported cases of oral MF (Table 2). At presentation of oral MF, the age ranged from 36 to 81 years, with a median of 64. Forty percent were women and 60% were men. Skin involvement universally preceded oral involvement with the exception of two cases ranging from 6 months to 20 years, with a median of 4 years.

At time of oral lesion diagnosis, 33% of patients had stage IB disease or lower and 11% had no active cutaneous disease. Most commonly, patients presented with oral lesions on the palate () and/or tongue (), which is consistent with the literature [8, 1119]. Sixty-one percent had multiple sites of oral involvement. Of the lesions identified, there were 12 tumor, 11 plaque, and 3 patch.

Our patient is remarkable in that he is in complete remission seven years after onset of oral lesion, which defies the median time of one year from diagnosis of oral lesion to death. Further, our patient had large cell transformation, which carries additional poor prognosis [20]. At the time of oral lesion development, no lymphadenopathy was present whereas in many of the reported cases, oral lesions occurred mostly in advanced stages of the disease.

Competing Interests

The authors declare that they have no competing interests.

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Copyright © 2016 Juri Bassuner et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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