Mycosis fungoides of t h e larynx LAWRENCE J. GORDON, MD, MOON LEE, MD,JOHN J. CONLEY, MD, JOE BUFILL, MD, and ERIC VONDERHEID, MD. New York, New York, and Philadelphia, Pennsylvania
M y c o s i s fungoides, a form of cutaneous T-cell lymphoma, is a malignant lymphoma predominantly affecting the skin. The causes and treatment modalities for this disorder are varied. Extracutaneous involvement by the tumor connotes a poor prognosis. We report an unusual case in which laryngeal involvement is the first sign of mycosis fungoides outside the skin.
From the Department of Otolaryngology (Dr. Gordon), New York Eye and Ear Infirmary; the Departments of Pathology (Dr. Lee), Surgery (Dr. Conley), and Medicine (Dr. Bufill), St. Vincent’s Hospital; and Division of Dermatology (Dr. Vonderheid), Hahnemann University.
CASE REPORT
An 81-year-old man presented in September 1990 with a 6-month history of progressive dysphagia, poor appetite, and 30-pound weight loss. Indirect Iaryngoscopy revealed an erythematous, submucosal swelling on the laryngeal surface of the epiglottis extending to the right pyriform sinus. There were no palpable cervical lymph nodes. The epiglottic lesion was demonstrated on CT scan (Fig. I). Received for publication May 22, 1991; revision received Feb. 2, 1992; accepted Feb. 25, 1992. Reprint requests: Lawrence J. Gordon, MD, Department of Otolaryngology, New York Eye and Ear Infirmary, 310 East 14th St., New York, NY 10003. 2314131651
Fig. 1. CT scan shows t h e epiglottic mass (arrow). 120
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Case Reports 121
Fig. 2. Epiglottic mycosis fungoides demonstrates a diffuse proliferation of large, atypical lymphoid cells (Hematoxylin-eosinstain; original magnification x 250). with irregularly folded nuclear membrane and prominent nucleoli [inset, Hematoxylin-eosinstain; original magnification x 1000).
Fig. 3. A, Touch preparation of the epiglottic lesion reveals large or medium-sized,atypical lymphoid cells with cerebriform nuclei (long arrows), pale cytoplasm, and mitosis (short arrow] [Wright-Giemsa stain; original magnification x 1000.) B, lmmunohistochemicai studies of paraffin section of the epiglottic lesion demonstratesstrong reactivity of the cell membrane with CD3 (open arrow] (Hematoxylin counterstained; original magnification x 1000).
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OtolaryngologyHead and Neck Surgery
122 Case Reports
Fig. 4. MRI of the lumbosacral spine (T,-weighted) sagittal sections. A, without gadolinium; B, with gadolinium. Abnormal enhancement is seen within the spinal canal along the conus and cauda equina, with areas of nodularity [arrow).These findings suggest carcinomatous leptomeningitis. Cutaneous lesions were diagnosed as mycosis fungoides (MF) in December 1986. Treatment included electron-beam radiotherapy, nitrogen mustard, and PUVA with regression of his cutaneous plaques. In early 1990, lesions developed on his trunk and extremities. Dysphagia subsequently developed as the result of the epiglottic lesion. A biopsy of the epiglottic lesion was performed; the pathology was read as consistent with acute and chronic inflammation. However, after repeat biopsy with immunohistochemical staining, the pathology was revised to mycosis fungoides. The lesion is characterized by a diffuse infiltration of large or medium-sized, atypical lymphoid cells with irregular cerebriform nuclei, prominent nucleoli, pale cytoplasm, and frequent mitoses (Figs. 2 and 3). Immunohistochemical studies showed positive staining with CD3 (T-cell antigen), and Leu22 (T-cell and B-cell subset antigen); and negative staining with LCA (leucocytic common antigen), UCHL-I (T-cell antigen), L26 (B-cell antigen) and LN2 (B-cell antigen) antibodies indicating the tumor is of T-cell origin. The loss of LCA and UCHL-1 indicates an aberrant T-cell phenotype consistent with lymphoma. Mycosis fungoides involving the epiglottis was diagnosed after original slides from his previous skin biopsies were reviewed. No evidence of other visceral involvement was found. The patient was treated with external-beam ionizing radiation to the larynx in October 1990 for a total of 27 Gy in nine fractions.
One month later he was readmitted for aspiration pneumonia as a result of his progressively debilitated state; there were no cranial neuropathies. He became increasingly lethargic and disoriented as his mental status declined. MRI scan of his brain and spinal cord was consistent with leptomeningeal MF (Fig. 4). His lumbar puncture revealed mycosis fungoides cells confirmed by cytology and T-cell studies. He continued to do poorly and died of pneumonia in November 1990. At autopsy, all organs, including brain, skin, and larynx, revealed no residual MF.
DISCUSSION Mycosis fungoides became recognized as a distinct pathological entity (a T-cell lymphoma) after 1970,' and since then the annual incidence of mycosis fungoides has increased 3.2 fold. It is more common among men, blacks, and older individuals.2 The etiology of mycosis fungoides is obscure; however, HTLVI and industrial exposure have been suggested as cont r i b u t o r ~ The . ~ classic form of this disease progresses to three stages: (1) the premycotic stage, (2) the plaque stage, and (3) the tumor ~ t a g eSeveral .~ treatment regimens have been used, including electron-beam and ionizing radiation, PUVA, topical nitrogen mustard, and systemic chemotherapy. Current evidence indicates that topical nitrogen mustard with total skin electron-beam
Downloaded from oto.sagepub.com at Purdue University on June 5, 2016
Volume 107 Number 1
Case Reports 123
July 1992
radiation may cure more than 30% of patients with early stage d i ~ e a s e . ~ , ~ Extracutaneous involvement of mycosis fungoides at autopsy is found in 71% of cases; the viscera most commonly involved in decreasing order are lung, spleen, liver, kidney, thyroid, pancreas, bone marrow, and heart.’ Mean survival in the presence of visceral disease is 25 months.8 Age, absolute lymphocyte count, extent of disease, and symptoms may have prognostic significance, but extent of disease is the only definite prognostic factor. Mycosis fungoides may involve the upper respiratory tract; intraoral involvement is the most common. l o Autopsy studies by Epstein et al.” revealed the larynx to be involved in terminal dissemination of the disease in three cases. Laryngeal involvement by mycosis fungoides has been reported involving the supraglottic larynx.12-’4As with other cases of visceral metastasis, this is a grave prognostic sign. REFERENCES 1. Edelson RL, Kirkpatrick CH, Shevach EM, et al. Preferential
cutaneous infiltration by neoplastic thymus-derived lymphocytes. Ann Intern Med 1974;80685-92. 2. Weinstock MA, Horn JW. Mycosis fungoides in the United States: Increasing incidence and descriptive epidemiology. JAMA 1988;260:42-6. 3. Fischmann AB, Bunn PA, Guccione JG, et al. Exposure to chem-
icals, physical agents, and biologic agents in mycosis fungoides and the Sezary syndrome. Cancer Treat Rep 1979;63:591-6. 4. Bazin E. Lecons Sur le traitment des Maladies Chroniques en General Affections de la Peau en Particulier par I’Emploi Compare des eaux Minerales I’Hydrotherapie et des Moyens Pharmaceutiques. Paris: Adrien Delahaye, 1870:425. 5 . Vonderheid EC, Van Scott EJ, Wallner PE, Johnson WC. A 10 year experience with topical mechlorethamine for mycosis fungoides: comparison with patients treated by total-skin electronbeam radiation therapy. Cancer Treat Rep 1979;63:681. 6. Worobec-Victor SM. Cutaneous T-cell lymphoma. N J Med 1989;86:395-9. 7. Rappaport H, Thomas LB. Mycosis fungoides: the pathology of extracutaneous involvement. Cancer 1974;34:1198-229. 8 . Suasville EA. Eddy JL, Makuck RW, et al. Hisopathologic staging at initial diagnosis of mycosis fungoides and the Sezary syndrome: definition of these distinctive prognostic groups. Ann Intern Med 1988;109:372-82. 9. Winkler CF, Bunn PA. Cutaneous T-cell lymphoma: a review. Crit Rev Oncol Hematol 1983;1:49-92. 10. Evans GE, Dolziel KL. Mycosis fungoides with oral involvement. Int J Oral Maxillofac Surg 1987;16:634-7. 11. Epstein EH Jr, Levin KL, Croft JD, Lutzner MA. Mycosis fungoides. Survival, prognostic features, response to therapy, and autopsy findings. Medicine 1972;15:61-72. 12. Hood AF, Mark GJ, Hunt JV. Larnygeal mycosis fungoides. Cancer 1979;43:1527-32. 13. Agarwal MK, Gupta S , Gupta OP. Mycosis fungoides of the larynx. Asian Med J 1982;294:268-71. 14. Ferlito A, Gianfranco R. Laryngeal involvement by mycosis fungoides. Ann Otol Rhino1 Laryngol 1986;95:275-7.
Downloaded from oto.sagepub.com at Purdue University on June 5, 2016
310
Otolaryngology Head and Neck Surgery March 1993
News and Announcements
held July 26-30, 1993, at the Tamarron Resort in Durango, Colorado. This 28 hour review and update will encompass all the clinically important areas of MR imaging. Important new concepts and pathological/imaging correlations in the body, musculoskeletal system, ENT, head and neck, brain, and spine will be explored. Daily case presentations will supplement these lectures and will serve to test the registrants' diagnostic abilities in MR imaging. This complete review of MR imaging will be presented by nationally recognized leaders in magnetic resonance imaging. As a result of this comprehensive review, registrants will become familiar with current applications of MR imaging and will be able to integrate many of these applications directly into their practice. Program chairmen for this presentation will be Robert Quencer, MD (University of Miami), Victor Haughton, MD (Medical College of Wisconsin). Twenty-eight credits of Category I will be available. For further information, please contact Marti Carter, CME, Inc., 11011 West Nort Ave., Milwaukee, Wisconsin 53226, or call (414) 771-9520. Ear, Nose, and Throat Diseases: 1993 Update
Children's Hospital of Pittsburgh will hold its 18th Annual Symposium, "Ear, Nose, and Throat Diseases in Children: A 1993 Update." This symposium will be held July 30-31, 1993. CME credits will be awarded.
For further information, please contact the Department of Pediatric Otolaryngology, Children's Hospital of Pittsburgh, 3705 Fifth Avenue at DeSoto St., Pittsburgh, Pennsylvania 15213, or call (412) 692-8577. Twenty-fifth Annual Meeting - Head and Neck Oncologists
The Association of Head and Neck Oncologists of Great Britain will sponsor the Twenty-fifth Annual Meeting of Head and Neck Oncology, to be held in Edinburgh, Scotland, United Kingdom, on August 23-26, 1993. International and local faculty will present extensive social and family programs. For further information, please contact Mr. P. J. Bradley, Honorary Secretary, Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital, Queens Medical Centre, Nottingham, NG7 2UH, England, or phone 0602421421. Sixth International Congress on Interventlonal Ultrasound
The Sixth International Congress on Interventional Ultrasound will be held in Copenhagen, Denmark, on September 7-10, 1993. For further information, please contact Christian Nolsoe, Congress Secretary, Department of Ultrasound, Herlev Hospital, University of Copenhagen, DK-2730 HerlevDenmark, or call + 45/ 44 53 53 00 ext. 3240.
CORRECTION
The Supplement to the December 1992 issue of the JOURNAL (Volume 107, Number 6, Part 2), incorrectly listed Dr. Bruce R. Gordon as Chief of Otolaryngology at the Massachusetts Eye and Ear Institute. Dr. Joseph Nadol is Chief of Otolaryngology at the Massachusetts Eye and Ear Infirmary. Dr. Gordon is Chief of Otolaryngology at Cape Cod Hospital.
M y c o s i s fungoides, a form of cutaneous T-cell lymphoma, is a malignant lymphoma predominantly affecting the skin. The causes and treatment modalities for this disorder are varied. Extracutaneous involvement by the tumor connotes a poor prognosis. We report an unusual case in which laryngeal involvement is the first sign of mycosis fungoides outside the skin.
From the Department of Otolaryngology (Dr. Gordon), New York Eye and Ear Infirmary; the Departments of Pathology (Dr. Lee), Surgery (Dr. Conley), and Medicine (Dr. Bufill), St. Vincent’s Hospital; and Division of Dermatology (Dr. Vonderheid), Hahnemann University.
CASE REPORT
An 81-year-old man presented in September 1990 with a 6-month history of progressive dysphagia, poor appetite, and 30-pound weight loss. Indirect Iaryngoscopy revealed an erythematous, submucosal swelling on the laryngeal surface of the epiglottis extending to the right pyriform sinus. There were no palpable cervical lymph nodes. The epiglottic lesion was demonstrated on CT scan (Fig. I). Received for publication May 22, 1991; revision received Feb. 2, 1992; accepted Feb. 25, 1992. Reprint requests: Lawrence J. Gordon, MD, Department of Otolaryngology, New York Eye and Ear Infirmary, 310 East 14th St., New York, NY 10003. 2314131651
Fig. 1. CT scan shows t h e epiglottic mass (arrow). 120
Downloaded from oto.sagepub.com at Purdue University on June 5, 2016
Volume 107 Number 1 July 1992
Case Reports 121
Fig. 2. Epiglottic mycosis fungoides demonstrates a diffuse proliferation of large, atypical lymphoid cells (Hematoxylin-eosinstain; original magnification x 250). with irregularly folded nuclear membrane and prominent nucleoli [inset, Hematoxylin-eosinstain; original magnification x 1000).
Fig. 3. A, Touch preparation of the epiglottic lesion reveals large or medium-sized,atypical lymphoid cells with cerebriform nuclei (long arrows), pale cytoplasm, and mitosis (short arrow] [Wright-Giemsa stain; original magnification x 1000.) B, lmmunohistochemicai studies of paraffin section of the epiglottic lesion demonstratesstrong reactivity of the cell membrane with CD3 (open arrow] (Hematoxylin counterstained; original magnification x 1000).
Downloaded from oto.sagepub.com at Purdue University on June 5, 2016
OtolaryngologyHead and Neck Surgery
122 Case Reports
Fig. 4. MRI of the lumbosacral spine (T,-weighted) sagittal sections. A, without gadolinium; B, with gadolinium. Abnormal enhancement is seen within the spinal canal along the conus and cauda equina, with areas of nodularity [arrow).These findings suggest carcinomatous leptomeningitis. Cutaneous lesions were diagnosed as mycosis fungoides (MF) in December 1986. Treatment included electron-beam radiotherapy, nitrogen mustard, and PUVA with regression of his cutaneous plaques. In early 1990, lesions developed on his trunk and extremities. Dysphagia subsequently developed as the result of the epiglottic lesion. A biopsy of the epiglottic lesion was performed; the pathology was read as consistent with acute and chronic inflammation. However, after repeat biopsy with immunohistochemical staining, the pathology was revised to mycosis fungoides. The lesion is characterized by a diffuse infiltration of large or medium-sized, atypical lymphoid cells with irregular cerebriform nuclei, prominent nucleoli, pale cytoplasm, and frequent mitoses (Figs. 2 and 3). Immunohistochemical studies showed positive staining with CD3 (T-cell antigen), and Leu22 (T-cell and B-cell subset antigen); and negative staining with LCA (leucocytic common antigen), UCHL-I (T-cell antigen), L26 (B-cell antigen) and LN2 (B-cell antigen) antibodies indicating the tumor is of T-cell origin. The loss of LCA and UCHL-1 indicates an aberrant T-cell phenotype consistent with lymphoma. Mycosis fungoides involving the epiglottis was diagnosed after original slides from his previous skin biopsies were reviewed. No evidence of other visceral involvement was found. The patient was treated with external-beam ionizing radiation to the larynx in October 1990 for a total of 27 Gy in nine fractions.
One month later he was readmitted for aspiration pneumonia as a result of his progressively debilitated state; there were no cranial neuropathies. He became increasingly lethargic and disoriented as his mental status declined. MRI scan of his brain and spinal cord was consistent with leptomeningeal MF (Fig. 4). His lumbar puncture revealed mycosis fungoides cells confirmed by cytology and T-cell studies. He continued to do poorly and died of pneumonia in November 1990. At autopsy, all organs, including brain, skin, and larynx, revealed no residual MF.
DISCUSSION Mycosis fungoides became recognized as a distinct pathological entity (a T-cell lymphoma) after 1970,' and since then the annual incidence of mycosis fungoides has increased 3.2 fold. It is more common among men, blacks, and older individuals.2 The etiology of mycosis fungoides is obscure; however, HTLVI and industrial exposure have been suggested as cont r i b u t o r ~ The . ~ classic form of this disease progresses to three stages: (1) the premycotic stage, (2) the plaque stage, and (3) the tumor ~ t a g eSeveral .~ treatment regimens have been used, including electron-beam and ionizing radiation, PUVA, topical nitrogen mustard, and systemic chemotherapy. Current evidence indicates that topical nitrogen mustard with total skin electron-beam
Downloaded from oto.sagepub.com at Purdue University on June 5, 2016
Volume 107 Number 1
Case Reports 123
July 1992
radiation may cure more than 30% of patients with early stage d i ~ e a s e . ~ , ~ Extracutaneous involvement of mycosis fungoides at autopsy is found in 71% of cases; the viscera most commonly involved in decreasing order are lung, spleen, liver, kidney, thyroid, pancreas, bone marrow, and heart.’ Mean survival in the presence of visceral disease is 25 months.8 Age, absolute lymphocyte count, extent of disease, and symptoms may have prognostic significance, but extent of disease is the only definite prognostic factor. Mycosis fungoides may involve the upper respiratory tract; intraoral involvement is the most common. l o Autopsy studies by Epstein et al.” revealed the larynx to be involved in terminal dissemination of the disease in three cases. Laryngeal involvement by mycosis fungoides has been reported involving the supraglottic larynx.12-’4As with other cases of visceral metastasis, this is a grave prognostic sign. REFERENCES 1. Edelson RL, Kirkpatrick CH, Shevach EM, et al. Preferential
cutaneous infiltration by neoplastic thymus-derived lymphocytes. Ann Intern Med 1974;80685-92. 2. Weinstock MA, Horn JW. Mycosis fungoides in the United States: Increasing incidence and descriptive epidemiology. JAMA 1988;260:42-6. 3. Fischmann AB, Bunn PA, Guccione JG, et al. Exposure to chem-
icals, physical agents, and biologic agents in mycosis fungoides and the Sezary syndrome. Cancer Treat Rep 1979;63:591-6. 4. Bazin E. Lecons Sur le traitment des Maladies Chroniques en General Affections de la Peau en Particulier par I’Emploi Compare des eaux Minerales I’Hydrotherapie et des Moyens Pharmaceutiques. Paris: Adrien Delahaye, 1870:425. 5 . Vonderheid EC, Van Scott EJ, Wallner PE, Johnson WC. A 10 year experience with topical mechlorethamine for mycosis fungoides: comparison with patients treated by total-skin electronbeam radiation therapy. Cancer Treat Rep 1979;63:681. 6. Worobec-Victor SM. Cutaneous T-cell lymphoma. N J Med 1989;86:395-9. 7. Rappaport H, Thomas LB. Mycosis fungoides: the pathology of extracutaneous involvement. Cancer 1974;34:1198-229. 8 . Suasville EA. Eddy JL, Makuck RW, et al. Hisopathologic staging at initial diagnosis of mycosis fungoides and the Sezary syndrome: definition of these distinctive prognostic groups. Ann Intern Med 1988;109:372-82. 9. Winkler CF, Bunn PA. Cutaneous T-cell lymphoma: a review. Crit Rev Oncol Hematol 1983;1:49-92. 10. Evans GE, Dolziel KL. Mycosis fungoides with oral involvement. Int J Oral Maxillofac Surg 1987;16:634-7. 11. Epstein EH Jr, Levin KL, Croft JD, Lutzner MA. Mycosis fungoides. Survival, prognostic features, response to therapy, and autopsy findings. Medicine 1972;15:61-72. 12. Hood AF, Mark GJ, Hunt JV. Larnygeal mycosis fungoides. Cancer 1979;43:1527-32. 13. Agarwal MK, Gupta S , Gupta OP. Mycosis fungoides of the larynx. Asian Med J 1982;294:268-71. 14. Ferlito A, Gianfranco R. Laryngeal involvement by mycosis fungoides. Ann Otol Rhino1 Laryngol 1986;95:275-7.
Downloaded from oto.sagepub.com at Purdue University on June 5, 2016
310
Otolaryngology Head and Neck Surgery March 1993
News and Announcements
held July 26-30, 1993, at the Tamarron Resort in Durango, Colorado. This 28 hour review and update will encompass all the clinically important areas of MR imaging. Important new concepts and pathological/imaging correlations in the body, musculoskeletal system, ENT, head and neck, brain, and spine will be explored. Daily case presentations will supplement these lectures and will serve to test the registrants' diagnostic abilities in MR imaging. This complete review of MR imaging will be presented by nationally recognized leaders in magnetic resonance imaging. As a result of this comprehensive review, registrants will become familiar with current applications of MR imaging and will be able to integrate many of these applications directly into their practice. Program chairmen for this presentation will be Robert Quencer, MD (University of Miami), Victor Haughton, MD (Medical College of Wisconsin). Twenty-eight credits of Category I will be available. For further information, please contact Marti Carter, CME, Inc., 11011 West Nort Ave., Milwaukee, Wisconsin 53226, or call (414) 771-9520. Ear, Nose, and Throat Diseases: 1993 Update
Children's Hospital of Pittsburgh will hold its 18th Annual Symposium, "Ear, Nose, and Throat Diseases in Children: A 1993 Update." This symposium will be held July 30-31, 1993. CME credits will be awarded.
For further information, please contact the Department of Pediatric Otolaryngology, Children's Hospital of Pittsburgh, 3705 Fifth Avenue at DeSoto St., Pittsburgh, Pennsylvania 15213, or call (412) 692-8577. Twenty-fifth Annual Meeting - Head and Neck Oncologists
The Association of Head and Neck Oncologists of Great Britain will sponsor the Twenty-fifth Annual Meeting of Head and Neck Oncology, to be held in Edinburgh, Scotland, United Kingdom, on August 23-26, 1993. International and local faculty will present extensive social and family programs. For further information, please contact Mr. P. J. Bradley, Honorary Secretary, Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital, Queens Medical Centre, Nottingham, NG7 2UH, England, or phone 0602421421. Sixth International Congress on Interventlonal Ultrasound
The Sixth International Congress on Interventional Ultrasound will be held in Copenhagen, Denmark, on September 7-10, 1993. For further information, please contact Christian Nolsoe, Congress Secretary, Department of Ultrasound, Herlev Hospital, University of Copenhagen, DK-2730 HerlevDenmark, or call + 45/ 44 53 53 00 ext. 3240.
CORRECTION
The Supplement to the December 1992 issue of the JOURNAL (Volume 107, Number 6, Part 2), incorrectly listed Dr. Bruce R. Gordon as Chief of Otolaryngology at the Massachusetts Eye and Ear Institute. Dr. Joseph Nadol is Chief of Otolaryngology at the Massachusetts Eye and Ear Infirmary. Dr. Gordon is Chief of Otolaryngology at Cape Cod Hospital.
