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David H. Aguirre P. Last Year MS University of Chile Gillian Lieberman MD Harvard Medical School OCTOBER 19, 2009 I. INTRODUCTION CASE REPORT OUR PATIENT: PRESENTATION • 23y/o M without significant PMHX. • He had a MVA with a head to steering wheel trauma. He suffered a left forehead laceration. Thereafter he had progressive swelling of the affected eye, peri‐orbital redness and sensation of sinus fullness. No fevers/chills/sweats/wt loss. He went to see an internist one month after the MVA. Ointment was prescribed. • The patient felt this helped so he continued to use the ointment for about a month. • With time, the patient’s eye was more swollen, so he presented to an ophthalmologist two months post‐MVA. The ophthalmologist prescribed oral antibiotic and requested a CT scan. The scan was performed at an outside hospital. OUR PATIENT: CT SCAN • CT posterior fossa and orbits: • Exophthalmos, inhomogeneous mass 3.5x3x2cm with rim enhancement and low‐density center, which is centered on the posterior roof of the orbit. • Referred to BIDMC and admitted. OUR PATIENT: HISTORY • PAST MEDICAL/SURGICAL HISTORY: • None • SOCIAL HISTORY: • • • • • • • • born/raised in Arizona moved to Massachusetts 2 years ago works as photo lab supervisor lives in Halifax with parents and son (22 months old) active, camps, fishes. Travel to Mexico once, years ago. no smoking, rare etoh, no ivdu lots of tattoos, about 2 per year. always in tattoo parlors. sexually active with women. currently monogamous. OUR PATIENT: HISTORY • PAST MEDICAL/SURGICAL HISTORY: • None • FAMILY HISTORY: • healthy son. • no diseases in mom/dad/siblings • ALLERGIES: • NKDA • MEDICATIONS at home: • po abx (cannot ascertain from history) OUR PATIENT: PHYSICAL EXAM • PHYSICAL EXAM: • • • • • • • • • • • Gen: NAD, normal respiratory effort. Mental status: Awake and alert, cooperative with exam, normal affect. Orientation: Oriented to person, place, and date. Speech intact. CN: Left peri‐orbital swelling and erythema; mild proptosis, chemosis; no audible bruit; no pulsation; II: Pupils equally round and reactive to light bilaterally. Visual fields are full to confrontation. III, IV, VI: Extraocular movements intact except for discreet limitation in extreme upward gaze on left. V, VII: Facial strength and sensation intact and symmetric. XII: Tongue midline without fasciculation. Motor: Normal bulk and tone bilaterally. No abnormal movements, tremors. Strength full power 5/5 throughout. No pronator drift. Sensation: Intact to light touch bilaterally. OUR PATIENT: MRI T1 Isointense lesion MRI: Sagittal T1 C(‐) MRI: Axial T1 C(‐) (PACS, Beth Israel Deaconess Medical Center. 2009.) MRI: Coronal T1 C(‐) OUR PATIENT: MRI Heterogeneous enhancement MRI: Sagittal T1 C(+) MRI: Axial T1 C(+) (PACS, Beth Israel Deaconess Medical Center. 2009.) MRI: Coronal T1 C(+) OUR PATIENT: SURGERY • Surgery: • Left‐sided 1.5 craniotomy for dissection and decompression • Intra‐operative image guidance with BrainLab • Microscopic dissection and decompression of middle temporal fossa, anterior skull base and orbital roof • Intra‐orbital decompression, dissection and evacuation of lesion that looks like chronic hematoma/abscess • Fresh frozen analysis confirmed PMN infiltrate consistent with chronic inflammation and abscess • Intra‐operative cultures were sent off for gram‐stain, culture and sensitivity • Pericranial autograft for repair • Autologous cranioplasty OUR PATIENT: MANAGEMENT • Management of the orbital abscess was started by the infectious disease team with Cefepime, AmBisome and Vancomycin. • All cultures negative! • …and the pathology examination… OUR PATIENT: PATHOLOGY • Pathology Examination, ten days later: • SOFT TISSUE, RETRO‐ORBITAL/CRANIAL FOSSA REGION, BIOPSY: • ATYPICAL HISTIOCYTIC AND EOSINOPHIL RICH INFILTRATE • “Overall, this is an unusual lesion, with histiocytic and eosinophilic rich infiltrate. The eosinophils form almost an abscess, while the histiocytes are in an organized bundles and display an unusual immunohistochemical profile characteristic of Langerhans Cell Histiocytosis” • Patient began LCH study, looking for other foci… OUR PATIENT: LCH STUDY Whole body BONE SCAN with Tc‐99m Skull BONE SCAN with Tc‐99m and X‐RAYS Whole body BONE SCAN with Tc‐99m (PACS, Beth Israel Deaconess Medical Center. 2009.) OUR PATIENT: DIAGNOSIS SO, THE PRELIMINARY DIAGNOSIS WAS: UNIFOCAL ORBITAL LANGERHANS CELL HISTIOCYTOSIS … and, what is LCH??? II. Langerhans Cell Histiocytosis DEFINITION LCH: DEFINITION • Histiocytosis X is a rare disease of unknown cause. • It is an uncommon proliferative disorder of bone marrow‐derived antigen‐presenting cells of the dendritic cell line, also known as Langerhans cells • The basic pathological feature of this disease is to form tumor masses or granulomatosis with destruction of the surrounding tissues. ELECTRON MICROSCOPE: Langerhans Cell (Siena et al. Massive ex-vivo generation of functional dendritic cells from mobilized CD34(+) blood progenitors for anticancer therapy. Exper. Hematol. 23 (14), Dec 1995, pp. 1463-1471) LCH: TERMINOLOGY • In 1953 L. Lichtenstein grouped three distinct clinical syndromes that show indistinguishable histology, under the term “Histiocytosis X”. • Eosinophilic Granuloma • Limited to bone (5‐15y) • Hand‐Schüller‐Christian disease • Multifocal bone lesions and extraskeletal involvement of RES and pituitary gland (1‐5y) • Letterer‐Siwe disease • Disseminated involvement of the RES with fulminant clinical course (<2y) • The actual term for these disease is “Langerhans Cell Histiocytosis” III. Langerhans Cell Histiocytosis EPIDEMIOLOGY LCH: EPIDEMIOLOGY • LCH is more common in children than in adults, with most cases being diagnosed before the age of 15 years. • The incidence is estimated at between 0.2 and 2 per 100,000 children under 15 years of age. • Large series tend to demonstrate a preponderance in males, sometimes as high as 60% to 70% of cases. • Is more common in whites of northern European descent. IV. Langerhans Cell Histiocytosis CLINICAL PRESENTATION LCH: SITES OF INVOLVEMENT • Unifocal (65%) • Bone (90%) • • • • • Skull Femur Pelvis Ribs Vertebrae – T > L > C • Others (10%) • Lung • Lymph node • Skin • Multifocal (45%) • Bone (60%) • Skull (>50%) • Bone + Soft Tissue (25%) • Soft Tissue (15%) LCH: SIGNS AND SYMPTOMS • Skull • Painful, immobile scalp mass that may have recently enlarged. • Spine • Local pain, back stiffness, torticollis, or kyphoscoliosis. • Pituitary • Diabetes insipidus, panhypopituitarism • Soft tissue and RES • Fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, skin lesions V. Langerhans Cell Histiocytosis PATHOLOGY LCH: PATHOLOGY • The key feature is the presence of Langerhans cells. • They show positive immunohistochemical staining for CD1a and S‐100 • The diagnostic gold standard feature is the ultra‐structural identification of Birbeck granules, which are 34nm wide tubular or tennis‐racket‐shaped intra‐cytoplasmic penta‐ laminar structures with a zipper‐like central core. LCH: PATHOLOGY Birbeck granules Langerhans Cell PATHOLOGY: Langerhans Cell (s100, CD1a) (D'Ambrosio, S. Soohoo, C. Warshall, A. Johnson, and S. Karimi. Craniofacial and Intracranial Manifestations of Langerhans Cell Histiocytosis: Report of Findings in 100 Patients. Am. J. Roentgenol., August 1, 2008; 191(2): 589 – 597) ELECTRON MICROSCOPE: Langerhans Cell (Birbeck granules) (Hasegawa K, Mitomi T, Kowa H, Motoori T, Yagisita S. A clinico-pathological study of adult histiocytosis X involving the brain. J Neurol Neurosurg Psychiatry.1993 Sep;56(9):1008–1012 ) VI. Neuroimaging CALVARIA LCH NEUROIMAGING: CALVARIA • In the calvarium, the lesions are round or oval lytic lesions, and have a characteristic beveled edges. X‐RAY: Lateral view CT: Axial, Bone Window (D'Ambrosio, S. Soohoo, C. Warshall, A. Johnson, and S. Karimi. Craniofacial and Intracranial Manifestations of Langerhans Cell Histiocytosis: Report of Findings in 100 Patients. Am. J. Roentgenol., August 1, 2008; 191(2): 589 – 597) LCH NEUROIMAGING: CALVARIA • On MRI, lesions are: • • • T1: isointense to gray matter T2: Isointense or hyperintense Variable enhancement after gadolinium administration MRI: Axial T1 C(‐) MRI: Axial T1 C(+) MRI: Axial T2 (D'Ambrosio, S. Soohoo, C. Warshall, A. Johnson, and S. Karimi. Craniofacial and Intracranial Manifestations of Langerhans Cell Histiocytosis: Report of Findings in 100 Patients. Am. J. Roentgenol., August 1, 2008; 191(2): 589 – 597) VII. Neuroimaging SKULL BASE LCH NEUROIMAGING: SKULL BASE • Radiologic findings: • Destructive, lytic “punched out” bone lesions CT: Axial, Bone Window CT: Axial, Soft Tissue Window (D'Ambrosio, S. Soohoo, C. Warshall, A. Johnson, and S. Karimi. Craniofacial and Intracranial Manifestations of Langerhans Cell Histiocytosis: Report of Findings in 100 Patients. Am. J. Roentgenol., August 1, 2008; 191(2): 589 – 597) LCH NEUROIMAGING: SKULL BASE • On MRI: • T1: variable signal intensity • T2: hyperintense • Homogeneous enhancement on CT and MRI after contrast administration MRI: Axial T1 C(‐) MRI: Axial T1 C(+) MRI: Coronal T1 C(‐) MRI: Coronal T1 C(+) (D'Ambrosio, S. Soohoo, C. Warshall, A. Johnson, and S. Karimi. Craniofacial and Intracranial Manifestations of Langerhans Cell Histiocytosis: Report of Findings in 100 Patients. Am. J. Roentgenol., August 1, 2008; 191(2): 589 – 597) VIII. Neuroimaging CRANIOFACIAL LCH NEUROIMAGING: FACIAL SWELLING • LCH typically presents as rapidly progressive facial swelling X‐RAY: Lateral view CT: Axial, Bone Window CT: Axial, Soft Tissue Window MRI: Axial T1 C(+) (D'Ambrosio, S. Soohoo, C. Warshall, A. Johnson, and S. Karimi. Craniofacial and Intracranial Manifestations of Langerhans Cell Histiocytosis: Report of Findings in 100 Patients. Am. J. Roentgenol., August 1, 2008; 191(2): 589 – 597) LCH NEUROIMAGING: MANDIBLE • The mandible is the second most common location of LCH • Mandible lesions tend to destroy alveolar bone, which produces the radiologic appearance of “floating teeth” X‐RAY: AP view X‐RAY: Oblique view (Khan AN, Chandramohan M, Turnbull I, MacDonald S. Eosinophilic Granuloma, Skeletal. eMedicine. May 14, 2008. Available at: http://emedicine.medscape.com/article/389350-overview. Accessed October 8, 2009) LCH NEUROIMAGING: ORBITAL • Orbital LCH is characteristically: • Isointense to gray matter on T1, T2, and proton density sequences • Enhance avidly on CT and MRI after contrast administration. MRI: Sagittal T1 C(‐) MRI: Sagittal T1 C(+) (PACS, Beth Israel Deaconess Medical Center. 2009.) IX. Neuroimaging CENTRAL NERVOUS SYSTEM LCH NEUROIMAGING: CNS • The most common CNS locations involved are the hypothalamic–pituitary axis and cerebellum. • Diabetes insipidus is the most common endocrine manifestation of LCH. LCH NEUROIMAGING: CNS • MRI findings in central diabetes insipidus are characterized: • • Lack of high signal intensity of the posterior pituitary on T1‐weighted images Often associated with enhancement and thickening of the pituitary stalk of greater than 3 mm NORMAL PITUITARY GLAND MRI: Sagittal T1 C(‐) MRI: Sagittal T1 C(‐) (PACS, Beth Israel Deaconess Medical Center. 2009.) MRI: Coronal T1 C(+) (D'Ambrosio, S. Soohoo, C. Warshall, A. Johnson, and S. Karimi. Craniofacial and Intracranial Manifestations of Langerhans Cell Histiocytosis: Report of Findings in 100 Patients. Am. J. Roentgenol., August 1, 2008; 191(2): 589 – 597) LCH NEUROIMAGING: CNS • Neurodegenerative changes are the second most frequent pattern. • Bilateral symmetric lesions in the cerebellum and basal ganglia of variable signal quality on MRI MRI: Axial T2 MRI: Axial T1 C(‐) MRI: Axial T2 (Grois N, Prayer D, Prosch H, Lassmann H. Neuropathology of CNS Disease in Langerhans Cell Histiocytosis. Brain. 2005; 128: 829-838) LCH NEUROIMAGING: CNS • Other more rare lesions includes parenchyma, meninges, pineal gland, choroid plexus… MRI: Coronal T2 MRI: Axial T1 C(+) MRI: Axial T1 C(+) MRI: Coronal T1 C(+) (Grois N, Prayer D, Prosch H, Lassmann H. Neuropathology of CNS Disease in Langerhans Cell Histiocytosis. Brain. 2005; 128: 829-838) MRI: Coronal FLAIR MRI: Coronal T1 C(‐) (Gunny R, Clifton A, Al-Memar A. Spontaneous Regression of Supratentorial Intracerebral Langerhans' Cell Histiocytosis. Br J Radiol. August 2004; 77(920): 685-7) MRI: Axial T1 C(‐) MRI: Axial T1 C(+) (Katati M, Martín JM, Pastor J, Arjona V. Isolated Langerhans Cell Histiocytosis of Central Nervous System. Neurocirugia. 2002; 13(6): 477-479) X. Neuroimaging SPINE LESIONS LCH NEUROIMAGING: SPINE • The lesions are similar to skull lesions. • More than 80% involves the vertebral body, and is usually limited to a single vertebral level. • Vertebra can be partially or completely collapsed (vertebra plana) LCH NEUROIMAGING: SPINE vertebra plana MRI: Sagittal T1 C(‐) MRI: Sagittal T1 C(‐) (Khan AN, Chandramohan M, Turnbull I, MacDonald S. Eosinophilic Granuloma, Skeletal. eMedicine. May 14, 2008. Available at: http://emedicine.medscape.com/article/389350-overview. Accessed October 8, 2009) XI. Langerhans Cell Histiocytosis DIFFERENTIAL DIAGNOSES LCH: DIFFERENTIAL DIAGNOSES LCH: DIFFERENTIAL DIAGNOSES Osteomyelitis X‐RAY: Lateral view CT: Axial, Bone Window CT: Axial, Bone Window (Chronic Osteomyelitis. PACS, Beth Israel Deaconess Medical Center. 2009.) Renal Cancer Metastasis MRI: Sagittal T1 C(‐) MRI: Coronal T1 C(+) (Skull Metastasis. PACS, Beth Israel Deaconess Medical Center. 2009.) XII. CONCLUSIONS CONCLUSIONS • LCH is a rare disease which mainly affect bone • The neuroimaging of LCH is, in most of the cases, non‐specific and it can vary depending on the location, specially on MRI • LCH should be considered as a differential diagnosis of craniofacial tumors ACKNOWLEDGEMENTS • Dr. E. Kasper • Dr. M. Anderson •Dr. R. Rojas •Dr. G. Lieberman XIII. REFERENCES REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. Binning MJ, Brockmeyer DL. Novel Multidisciplinary Approach for Treatment of Langerhans Cell Histiocytosis of the Skull Base. Skull Base. January 2008; 18(1): 53‐8. D'Ambrosio N, Soohoo S, Warshall C, Johnson A, Karimi S. Craniofacial and Intracranial Manifestations of Langerhans Cell Histiocytosis: Report of Findings in 100 Patients. Am J Roentgenol. August 2008; 191(2): 589 – 597. Grois N, Tsunematsu Y, Barkovich AJ, Favara BE. Central Nervous System Disease in Langerhans Cell Histiocytosis. Br J Cancer Suppl. 1994; 23: S24‐8. Grois N. Central Nervous System Disease in LCH. Histiocytosis Association of America. 2002. Available at: http://www.histio.org/site/c.kiKTL4PQLvF/b.1851567/k.AED5/Central_Nervous_System_Disease_in_LCH.htm. Accessed September 29, 2009. Grois N, Prayer D, Prosch H, Lassmann H. Neuropathology of CNS Disease in Langerhans Cell Histiocytosis. Brain. 2005; 128: 829‐838. Gunny R, Clifton A, Al‐Memar A. Spontaneous Regression of Supratentorial Intracerebral Langerhans' Cell Histiocytosis. Br J Radiol. August 2004; 77(920): 685‐7. Hasegawa K, Mitomi T, Kowa H, Motoori T, Yagisita S. A Clinico‐pathological Study of Adult Histiocytosis X Involving the Brain. J Neurol Neurosurg Psychiatry. September 1993; 56(9): 1008–1012. Katati M, Martín JM, Pastor J, Arjona V. Isolated Langerhans Cell Histiocytosis of Central Nervous System. Neurocirugia. 2002; 13(6): 477‐479. Khan AN, Chandramohan M, Turnbull I, MacDonald S. Eosinophilic Granuloma, Skeletal. eMedicine. May 14, 2008. Available at: http://emedicine.medscape.com/article/389350‐overview. Accessed October 8, 2009. Kulkarni AV, Hawkins C. Chapter 100: Langerhans Cell Histiocytosis. In: Berger MS, Prados MD, eds. Textbook of Neuro‐Oncology. 1st ed. Philadelphia: Elsevier Saunders; 2004. Lichtenstein L. Histiocytosis X: integration of eosinophilic granuloma of bone, "Letterer‐Siwe disease", and a single nosologic entity. Arch Pathol. 1953; 56: 84‐102. Lieberman PH, Jones CR, Steinman RM. Langerhans Cell (eosinophilic) Granulomatosis. A Clinicopathologic Study Encompassing 50 years. Am J Surg Pathol. 1996; 20: 519‐552. Siena et al. Massive ex‐vivo generation of functional dendritic cells from mobilized CD34(+) blood progenitors for anticancer therapy. Exper. Hematol. 23 (14), Dec 1995, pp. 1463‐1471. THANKS!