David H. Aguirre P. Last Year MS University of Chile Gillian Lieberman MD Harvard Medical School
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1 David H. Aguirre P. Last Year MS University of Chile Gillian Lieberman MD Harvard Medical School OCTOBER 19, 2009
2 I. INTRODUCTION CASE REPORT
3 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.
4 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.
5 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.
6 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)
7 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.
8 OUR PATIENT: MRI T1 Isointense lesion MRI: Sagittal T1 C( ) MRI: Axial T1 C( ) MRI: Coronal T1 C( ) (PACS, Beth Israel Deaconess Medical Center )
9 OUR PATIENT: MRI Heterogeneous enhancement MRI: Sagittal T1 C(+) MRI: Axial T1 C(+) MRI: Coronal T1 C(+) (PACS, Beth Israel Deaconess Medical Center )
10 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
11 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
12 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
13 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 )
14 OUR PATIENT: DIAGNOSIS SO, THE PRELIMINARY DIAGNOSIS WAS: UNIFOCAL ORBITAL LANGERHANS CELL HISTIOCYTOSIS and, what is LCH???
15 II. Langerhans Cell Histiocytosis DEFINITION
16 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 )
17 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
18 III. Langerhans Cell Histiocytosis EPIDEMIOLOGY
19 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.
20 IV. Langerhans Cell Histiocytosis CLINICAL PRESENTATION
21 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%)
22 LCH: SIGNS AND SYMPTOMS Skull Spine Painful, immobile scalp mass that may have recently enlarged. Local pain, back stiffness, torticollis, or kyphoscoliosis. Pituitary Diabetes insipidus, panhypopituitarism Soft tissue and RES Fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, skin lesions
23 V. Langerhans Cell Histiocytosis PATHOLOGY
24 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 pentalaminar structures with a zipper like central core.
25 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): ) 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): )
26 VI. Neuroimaging CALVARIA
27 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): )
28 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): )
29 VII. Neuroimaging SKULL BASE
30 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): )
31 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): )
32 VIII. Neuroimaging CRANIOFACIAL
33 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): )
34 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, Available at: Accessed October 8, 2009)
35 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 )
36 IX. Neuroimaging CENTRAL NERVOUS SYSTEM
37 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.
38 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( ) MRI: Coronal T1 C(+) (PACS, Beth Israel Deaconess Medical Center ) (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): )
39 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: )
40 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: ) MRI: Coronal FLAIR MRI: Coronal T1 C( ) MRI: Axial T1 C( ) MRI: Axial 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) (Katati M, Martín JM, Pastor J, Arjona V. Isolated Langerhans Cell Histiocytosis of Central Nervous System. Neurocirugia. 2002; 13(6): )
41 X. Neuroimaging SPINE LESIONS
42 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)
43 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, Available at: Accessed October 8, 2009)
44 XI. Langerhans Cell Histiocytosis DIFFERENTIAL DIAGNOSES
45 LCH: DIFFERENTIAL DIAGNOSES
46 LCH: DIFFERENTIAL DIAGNOSES Osteomyelitis X RAY: Lateral view CT: Axial, Bone Window CT: Axial, Bone Window (Chronic Osteomyelitis. PACS, Beth Israel Deaconess Medical Center ) Renal Cancer Metastasis MRI: Sagittal T1 C( ) MRI: Coronal T1 C(+) (Skull Metastasis. PACS, Beth Israel Deaconess Medical Center )
47 XII. CONCLUSIONS
48 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
49 ACKNOWLEDGEMENTS Dr. E. Kasper Dr. M. Anderson Dr. R. Rojas Dr. G. Lieberman
50 XIII. REFERENCES
51 REFERENCES 1. Binning MJ, Brockmeyer DL. Novel Multidisciplinary Approach for Treatment of Langerhans Cell Histiocytosis of the Skull Base. Skull Base. January 2008; 18(1): 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): Grois N, Tsunematsu Y, Barkovich AJ, Favara BE. Central Nervous System Disease in Langerhans Cell Histiocytosis. Br J Cancer Suppl. 1994; 23: S Grois N. Central Nervous System Disease in LCH. Histiocytosis Association of America Available at: Accessed September 29, Grois N, Prayer D, Prosch H, Lassmann H. Neuropathology of CNS Disease in Langerhans Cell Histiocytosis. Brain. 2005; 128: Gunny R, Clifton A, Al Memar A. Spontaneous Regression of Supratentorial Intracerebral Langerhans' Cell Histiocytosis. Br J Radiol. August 2004; 77(920): 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): Katati M, Martín JM, Pastor J, Arjona V. Isolated Langerhans Cell Histiocytosis of Central Nervous System. Neurocirugia. 2002; 13(6): Khan AN, Chandramohan M, Turnbull I, MacDonald S. Eosinophilic Granuloma, Skeletal. emedicine. May 14, Available at: overview. Accessed October 8, Kulkarni AV, Hawkins C. Chapter 100: Langerhans Cell Histiocytosis. In: Berger MS, Prados MD, eds. Textbook of Neuro Oncology. 1st ed. Philadelphia: Elsevier Saunders; Lichtenstein L. Histiocytosis X: integration of eosinophilic granuloma of bone, "Letterer Siwe disease", and a single nosologic entity. Arch Pathol. 1953; 56: Lieberman PH, Jones CR, Steinman RM. Langerhans Cell (eosinophilic) Granulomatosis. A Clinicopathologic Study Encompassing 50 years. Am J Surg Pathol. 1996; 20: 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
52 THANKS!
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