NK/T-cell lymphomas are a group of clonal proliferations of NK- or, rarely, T-cell types and have peculiar clinicopathologic features. Most common site of involvement is the upper aerodigestive tract (nasal cavity, nasopharynx, paranasal sinuses, and palate). Association of autoimmune paraneoplastic disorders with NK/T-cell lymphomas is not well studied. Our patient was diagnosed with NK/T-cell lymphoma stage IV with skin involvement and treated frontline with CHOEP regimen. While he was under treatment, two immune complications presented: anterior uveitis of autoimmune origin refractory to steroids and myositis in lower limbs muscles. Autologous transplantation was rejected due to confirmed early relapse after first-line treatment, and the patient received second-line treatment according to the SMILE scheme, reaching complete response after four cycles. The patient underwent allogeneic transplantation and at the time of manuscript preparation is alive despite multiple complications. The disease should be suspected in patients with rhinitis or recurrent sinusitis, and early biopsy is recommended for all patients to avoid a delay in diagnosis. Our patient also presented symptoms of disease progression after first-line treatment, representing a paraneoplastic process, a very rare phenomenon in T-type lymphomas. This case is novel for the appearance of an inflammatory myositis, a histologically verified paraneoplastic phenomenon that responded to treatment for lymphoma.
NK/T-cell lymphomas are a group of clonal proliferations of NK- or, rarely, T-cell types and have peculiar clinicopathologic features. The most common site of involvement is the upper aerodigestive tract, including the nasal cavity, nasopharynx, paranasal sinuses, and palate [
We report a very rare case of stage IV nasal-type NK/T-cell lymphoma with metastatic lesions in the right leg mimicking cellulitis on initial clinical-radiologic diagnostic workups that included radiology studies. To our knowledge, this is the first report of cutaneous involvement of nasal-type NK/T-cell lymphoma presenting as myositis of the leg.
A 56-year-old Ecuadorian man was referred to our department with a 7-year history of bilateral nasal respiratory insufficiency resistant to multiple treatments (antibiotics, steroids, etc.). In August 2013, anterior septal perforation (11 × 12 mm) was observed using computed tomography (CT). Nasal biopsy was proposed but the patient was lost to follow-up. In September 2014, the patient presented to the dermatology department with complaints of progressive skin lesions on the trunk, legs, and glands that consisted of subcutaneous nodules tending to ulcerate. Palate perforation was also observed upon examination. Biopsy of the lesions and a CT scan were performed. A few days later, the patient reported to the emergency department due to ulcers on the palate and fever reaching 39°C. Septum and palate perforation were observed on CT images (Figures
(a-b) Nasal lymphoma showing an initial ulcer that perforated into the oral cavity, opening a passage between the oral cavity and the nasal cavity. (c) Cutaneous manifestation of nasal-type extranodal NK/T-cell lymphoma. (d) Skeletal muscle fascicles revealing markedly distorted overall architecture with inflammatory interstitial infiltrate and endo and perimysial expansion. Perivascular lymphocytic inflammatory cluster with no signs of vasculitis. Myopathic changes suggestive of inflammatory myopathy. EBER negative. (e) Flow cytometry analysis of vitreous humor specimen: analysis is performed on cells consistent with leukocytes by FSC versus SSC and CD45. Flow cytometry demonstrates an aberrant NK-cell population (highlighted in red) with the following immunophenotype: CD3s−, CD56 (bright), CD7−, CD45+, HLA-DR−, CD5−, CD8−, and CD4− (see complete immunophenotype in text). Cells highlighted in cyan show a minor population of not aberrant NK cells and cells in red show reactive T cells. (f) MRI of the lower limbs revealing myositis infectious between the extensor digitorum longus and peroneus longus.
Additionally, on physical examination the patient presented necrotic, ulcerated, cutaneous nodules (Figure
While he was waiting for consolidation therapy with autologous stem-cell transplantation, he developed very painful skin lesions that consisted of cutaneous infiltration by lymphoma cells and suffered again of blurred vision. New ophthalmic assessment discovered a posterior uveitis. Analysis by flow cytometry immunophenotype of vitrectomy sample (vitreous humor) demonstrated elevated leukocyte count with an aberrant NK-cell population comprising approximately 25% of the cells. This atypical population was within the lymphoid cell gate, with higher forward scatter properties as the residual normal lymphoid cells. The aberrant NK-cell population expressed CD45, CD56 (bright), and CD2 and was negative for CD7, CD3s, CD3cy, TCR alpha-beta CD4, CD5, CD8, TCR gamma-delta, CD16, CD10, CD14, CD19, CD20, CD34, and HLA-DR (Figure
The most common hematologic malignancies associated with dermatomyositis/myositis are B-cell lymphomas [
Reported cases with autoimmune complications.
Author | Age | Sex | Location | Previous symptoms | Autoimmune complications | Time to diagnosis | Treatment | Survival | Cause of death |
---|---|---|---|---|---|---|---|---|---|
Park et al. [ |
40 | W | Skin | High fever, proximal muscle weakness, multiple skin plaques with bullae and serous discharge | Dermatomyositis and hemophagocytic syndrome | 24 months | CHOP → steroid, antibiotics, gamma globulin, oral cyclosporin | 7 days | Hepatic failure, renal failure, pancytopenia, massive pleural effusion |
Kim et al. [ |
64 | M | Skin | Painful swelling and redness of the left upper arm | Cellulitis or fasciitis | 5 months | Antibiotics → L-asparagine chemotherapy | n.r. | n.r. |
Chan et al. [ |
68 | W | Muscle | Forearm swelling and bilateral facial swelling | Polymyositis | 4-5 weeks | Prednisolone | Few days | Fulminant hemophagocytic syndrome |
Spadigam et al. [ |
49 | M | Skin | Intermittent fever, nasal stuffiness, epistaxis and hemifacial pain, nasolabial lesion | Inflammatory myofibroblast | 3 months | Surgery | 2 weeks | Postoperative complications |
Fei et al. [ |
83 | W | Lung | Skin ulceration and intermittent fever | Panniculitis | 12 months | Antibiotics → patient refused treatment | 35 days | Multiorgan failure |
Chow et al. [ |
27 | W | Skin | Intermittent fever, occasional night sweats, nasal congestion and hoarseness, skin nodules | Panniculitis or sarcoidosis | 3 months | Antiviral/antibiotic → CHOP → ICE | 7 months | Secondary hemophagocytic syndrome |
Current | 56 | M | Skin | Bilateral nasal respiratory insufficiency, anterior septal perforation, skin lesions | Myositis and uveitis | 13 months | CHOP → SMILE → BMT | 30 months | Alive |
Our patient presented paraneoplastic lesions, inflammatory myositis, and anterior uveitis, not described in the literature; these lesions resolved fully after targeted therapy for lymphoma. In addition, we suspect that the anterior uveitis also had an immune origin, as uveitis did not respond to treatment with valacyclovir and improved with chemotherapy.
In conclusion, we present a case of stage IV nasal-type NK/T-cell lymphoma. This entity has a very low incidence in our environment and, despite its sensitivity to radiotherapy, prognosis is poor. The disease should be suspected in patients with rhinitis or recurrent sinusitis, and early biopsy is recommended for all patients to avoid a delay in diagnosis. Our patient also presented symptoms of disease progression after first-line treatment, representing a paraneoplastic process, a very rare phenomenon in T-type lymphomas. This case is novel for the appearance of an inflammatory myositis, a histologically verified paraneoplastic phenomenon that responded to treatment for lymphoma. This case is also noteworthy because the patient is still alive nine months after allogeneic bone marrow transplantation without evidence of relapse, so this strategy should be the treatment of choice in fit patients with available donor [
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All authors declare that there is no conflict of interests regarding the publication of this paper.
Maria José Gómez-Crespo and Aránzazu García-Raso contributed equally in the preparation of the manuscript. The authors confirm that they all participated in the preparation of the manuscript.