Download Neuroimaging of Langerhans Cell Hystiocytosis

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:
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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:
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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%)
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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:
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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:
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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
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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.
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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.
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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!