A Rare Case of Mycosis Fungoides in the Oral Cavity and Small Intestine Complicated by Perforation

Abstract

Extracutaneous involvement in mycosis fungoides (MF) carries a poor prognosis. Oral and gastrointestinal (GI) tract lesions are both rare locations of disease. We describe the clinical findings of one case with oral and GI MF complicated by perforation after systemic antineoplastic treatment, and review the relevant literature. The patient had a 1-year history of MF before development of tongue and palate tumors. He was treated with local electron beam radiation, but re-presented to the hospital after what was found to be small intestine perforation following systemic antineoplastic therapy. The case reveals key insights into the progression and complications of lymphomas with GI tract involvement.

Introduction

Mycosis fungoides (MF) is a cutaneous, extranodal, insidious non-Hodgkin T-cell lymphoma [1, 2]. Almost any location in the body can be infiltrated by MF, including the oral cavity and the gastrointestinal (GI) tract [3].

Oral cavity and GI involvement of MF are rare as separate entities [3, 4, 5]. Individuals with extracutaneous lesions have a poor prognosis. We present one case of MF with both oral and visceral involvement, with complication of intestine perforation after treatment.

Case Report

A 38-year-old man with congenital ichthyosis and presumed psoriasis presented in late 2015 with erythroderma, numerous plaques, and tumors affecting his body and face. His skin was generally denuded and ulcerated on the arms and trunk. The lesions were weeping serous fluid.

He was admitted for methicillin-resistant Staphylococcus aureus skin infection and treated with whirlpool therapy and intravenous antibiotics. Initial histology was consistent with psoriasiform epidermal hyperplasia with spongiosis. Although the biopsy showed exocytosis and lymphocytes, there was no large-cell transformation. A second biopsy was consistent with cutaneous T-cell lymphoma. The T-cell analysis showed cells with CD3 and some CD4 expression and without CD7 or CD8 expression. Approximately 5–10% of the cells expressed CD30. Most of the cells expressed TCR-β. No gene rearrangements were noted. In situ hybridization for EBV RNA (EBER) was negative. Flow cytometry of the blood showed minimal blood involvement. The patient was treated with 32 Gy of total body skin electron beam radiation. There was complete clearing of his lesions. Unfortunately, stem cell transplantation was cost-prohibitive.

He returned to his home country after 2 months but re-presented 1 month later with dysphagia, abdominal pain, and a 20-pound weight loss. The skin had many new small tumors <1 cm and annular plaques. His mouth was remarkable for two linear white plaques with an erythematous base on the pharynx above the uvula. Ulcerative lesions were present on his edematous epiglottis and left arytenoid. He had a geographic tongue with lack of pili and white-to-yellowish plaque-like lesions along the midline and left lateral anterior dorsal surface (Fig 1).

Fig. 1.

Lesions of the tongue and palate before (left) and after (right) treatment with palliative radiation to the oropharynx.

Biopsy of the anterior dorsal tongue was filled with atypical lymphocytes extending to the basal layer of the epithelium. There were occasional intraepithelial atypical lymphocytes with irregular nuclei. Immunohistochemistry of the atypical lymphocytes showed 40% with CD30 positivity. The malignant cells were double negative for both CD4 and CD8, expressed BF-1, and had some labeling for T-cell intracellular antigen, granzyme B, and CD56. This was consistent with epidermotropic cutaneous T-cell lymphoma. Restaging imaging showed lymphomatous involvement in his small intestine (Fig 2). He received 12 Gy of palliative radiation to his oropharynx, 1 dose of brentuximab vedotin anti-CD30 antibody (1.8 mg/kg i.v.), and one cycle of cyclophosphamide-etoposide-vincristine-prednisone (CEOP).

Fig. 2.

Two views of restaging imaging showing increased fludeoxyglucose tracer uptake in the small intestine.

The patient presented to the emergency room with acute abdominal pain 2 weeks after the brentuximab and CEOP administration. His CT scan showed significant progression of tumor involving the intestine, evidence of obstruction, and intestine perforation with free intraperitoneal air in the region of the small intestine. He underwent emergent abdominal exploration and perforation repair.

After perforation repair, the patient received a second cycle of CEOP. However, he had progression in multiple areas of the skin with tumors. The CEOP was discontinued and gemcitabine 1,000 mg/m² was started. He ultimately had improvement in functional status and skin tumor burden. After completing two cycles of the gemcitabine nearly 5 months after his oral lesions had initially appeared and 3 months after the perforation, he was admitted to the hospital again with abdominal pain. A second bowel perforation was diagnosed and medically managed by his care team. He was subsequently placed back on a second cycle of brentuximab vedotin after biopsy of the right forearm had shown MF with atypical lymphocytes that were positive for CD3 and CD7, mostly negative for CD4 and CD8, and expressed CD30 in approximately 45% of lymphocytes. He completed the second cycle at around the time of submission of the manuscript. His prognosis was guarded.

Discussion

We report the first case of simultaneous involvement of MF in the oral cavity and small intestine. This was the fourth case of intestinal perforation related to MF. However, this case provides insight into the disease process and the complications of lymphomas with GI tract involvement.

The MF disease process has a relatively predictable pattern of three phases: erythematous or eczematous rash, infiltrated plaques, and cutaneous tumors [2]. Ultimately, the MF disease process results in diffuse visceral and lymphatic involvement [3, 4, 6]. This outcome is the hallmark of end-stage disease, which is characterized by atypical lymphocytes that lack the epidermotropism of early-stage MF [7].

Oral cavity involvement of MF is a rare event, a predictor of poor prognosis, and found in late-stage disease. There were only 42 reported cases of oral MF including our patient; most cases of MF in the oral cavity have been described as affecting the tongue and palate, as in our patient [3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20].

Extranodal non-Hodgkin lymphoma most commonly occurs in the GI tract, with the small intestine being the most common site of involvement [21]. There have been reports of MF cases throughout the GI tract, including the small intestine (Table 1) [3, 4, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43]. Briefly, there have been 67 cases of GI MF in the reported literature. The most common site was the small intestine, as seen in our patient. The majority of cases in the small intestine presented with abdominal pain and ultimately experienced death up to 6 months after presentation with GI MF. Our patient presented similarly, with advanced-stage disease and with abdominal pain shortly after treatment with radiation, brentuximab, and CEOP. He had initial resolution of his skin and oral lesions on gemcitabine, but had disease recurrence with resulting perforation less than 6 months later. His prognosis was guarded.

Table 1.

Summary of reported cases of mycosis fungoides in the gastrointestinal tract

Reference (first author)	Cases reported, n	Site of involvement					Presentation	Complication	Treatment	Outcome
		esophagus	stomach small	intestine	large intestine	rectum/anus
Long [6]	4	2	2	–	–	–	–	hemorrhage	–	death (autopsy series)
Epstein [4]	30	7	7	13	2	1	–	–	–	death (autopsy series)
Rappaport [3]	11	1	4		6a	–	–	–	–	death (autopsy series)
Ganz [31]	1	1	1	1	1	–	diarrhea	gastric ulcer, colonic ulcers	CT	death after 4 months
Ishida [27]	1	1	–	–	–	–	dysphagia	esophageal ulcer	CT, radiation	death
Kim [39]	1	1	–	–	–	–	dysphagia, odynophagia, weight loss	–	–	–
Chéridjian [35]	1b	1b	–	–		–	odynophagia	–	–	–
Kressin [37] (case 1)	1	1	–	–	–	–	dysphagia	–	–	–
Kressin [37] (case 2)	1	1	–	–	–	–	–	–	–	–
Hood [36]	1	1	–	–	–	–	dysphagia	ulcerations with Candida	not specified	death 4 years after mycosis fungoides onset
Dereure [40]	1	1	–	–	–	–	dysphagia	ulcerated nodules	CT	death
Redleaf [30]	1	1	–	–	–	–	dysphagia, hoarseness	–	radiation	–
Vasishta [42]	1	–	1	–	–	–	diarrhea	upper gastrointestinal bleed, ileus	–	death after 2 days
Wiedmann [41]	1	–	1	–	–	–	abdominal pain	perforation	–	–
Slater [28] (case 1)	1	–	1	–	–	–	abdominal pain	gastric ulcer	–	–
Slater [28] (case 2)	1	–	–	1	–	–	weight loss, diarrhea	–	CT	death after 6 cycles of CT
Chen [29]	1	–	–	1	–	–	abdominal pain	perforation	–	death after 2 months
Camisa [22]	1	–	–	1	–	–	abdominal pain	perforation	laparotomy, resection	death after 30 days
Velagapudi [25]	1	–	–	1	–	–	abdominal pain, emesis, constipation	small intestine obstruction	laparotomy, resection	death after 6 months
Newton [33]	1	–	–	1	–	–	abdominal pain	perforation	laparotomy, cortisone	death after 5 days
Gómez Venegas [23]	1	–	–	1	–	–	fever, fatigue	fistula	–	death after 20 days
Engle [38]	1	–	–	1	–	–	abdominal pain, nausea, vomiting	stricture of colon	CT, radiation	death after 4 months
Branscheid [34]	1	–	–	–	1	–	–	–	–	–
Tan [43]	1	–	–	–	–	1	abdominal pain, constipation, diarrhea	–	radiation	–
Current report	1	–	–	1	–	–	abdominal pain	perforation, obstruction	laparotomy, CT	subsequent recurrent disease and perforation
Total	67c	19	17	22	4	2

CT, chemotherapy.

^aNot specified as to the site of lesion (small versus large intestine), so excluded from final tallies in “Total” row.

^bProbable case of mycosis fungoides.

^cGrand total of gastrointestinal mycosis fungoides cases.

The complications of GI involvement include hemorrhage, obstruction, and perforation [6, 22, 44, 45]. Perforation from lymphoma involvement in the GI tract was a well-known complication, with the majority occurring as the first sign of GI involvement and not as a result of antineoplastic treatment [46, 47, 48, 49, 50, 51, 52, 53, 54]. The small intestine was the most common site of perforation [53, 54]. Perforation as a result of therapy can occur shortly after treatment, usually within a few weeks, as in our patient [53, 54]. The risk of perforation from the cytotoxic agent seems to be less than that of the tumor's presence itself, but clinicians should nonetheless be cautious in treating patients with lymphoma in the GI tract.

Our patient initially had intestine perforation 2 weeks after treatment with brentuximab and CEOP. He subsequently had a second perforation after gemcitabine, a nucleoside analogue chemotherapy agent. Although patients with MF are at risk of secondary lymphomas [55], the timing and good response to brentuximab and gemcitabine suggested that the lesions were MF and that the perforations were likely a result of the antineoplastic agents.

To our knowledge, there have been three case reports of intestinal perforation from MF involvement of the small intestine [22, 33, 41]. One of the cases was described in the German-language literature [41]. Of the other patients presented in the two English-language case reports, the first developed perforation with peritonitis approximately 1 year after initial MF treatment [22]. It does not appear that this patient's perforation was related to treatment. However, the second patient presented with perforation of the small intestine after prednisone treatment in a similar fashion to our patient [33].

In conclusion, MF involving both the oral palate and the small bowel is extremely rare. This unique patient had coexistent oral and small bowel lesions apparent on PET scan. The latter was accompanied by abdominal pain and resulted in serious, life-threatening bowel perforations that had been preceded by combination therapy with antibody and multi-agent chemotherapy.

Statement of Ethics

The participant provided written informed consent for use of his case and images per University of Texas MD Anderson Cancer Center (UTMDACC) guidelines. Institutional review board approval was not needed for this study.

Disclosure Statement

The authors certify that they have no sponsorship or funding arrangements relating to their research. All authors have no disclosures regarding conflicts of interest.