case of the month december 2017 - cytology.ch...case of the month december 2017 dre ana barrigón...
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Case of the month December 2017
Dre Ana Barrigón Benítez Institut universitaire de pathologie, Lausanne
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Clinical history
30 years-old male, presenting with a right
lower pulmonary mass.
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Investigation
• Bronchial aspiration, brushing and biopsy are performed.
• Cytological examination shows atypical spindle cells with
elongated nuclei, prominent nucleolus, binucleation and
intranuclear inclusions within a background of mixed
inflammatory infiltrate and myxoid stroma.
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Bronchial aspiration
PAP, 20x. Spindle cells in a myxoid stroma.
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PAP, 40x.
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Granuloma?
PAP, 200x.
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Bronchial aspiration
PAP 400x. Spindle cells with elongated nuclei (sometimes binucleated) and prominent nucleolus.
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Bronchial aspiration
PAP 400x. Mild irregularity of nuclear contours. Intranuclear inclusions (arrow). Mixed inflammatory infiltrate.
Giant cell
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PAP, 400x. Intranuclear inclusions (arrow).
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PAP, 400x.
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PAP, 200x.
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PAP, 400x.
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PAP, 400x.
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Cell-block H&E, 20x. Cells in a myxoid stroma. Pigment.
H&E, 400x. Spindle cells with elongated nuclei, prominent nucleolus and binucleation. Mixed inflammatory background.
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H&E, 400x Cell-block
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H&E, 400x Cell-block
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H&E, 400x
Cell-block
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H&E, 400x
Cell-block
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ALK: cytoplasmic and nuclear staining, 400x
Immunocytochemistry Cell-block
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Immunocytochemistry
ALK: cytoplasmic and nuclear staining, 400x
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Immunocytochemistry
• Cells are positive for:
– Vimentine & ALK (strong).
– AML, EMA et focally S100.
– Calponine (weak).
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Histology
• Bronchial biopsies are also performed.
• Diffuse infiltration of spindle-cells, with
elongated nucleus and some intranuclear inclusions in a myxoid matrix
(same aspect than the cell-bloc)
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ALK rearrengement – break-apart FISH
Biopsy
Courtesy dr. Letovanec, dr. Bisig
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Cytologic Diagnostic
Mesenchymal tumor, ALK-positive, consistent with
inflammatory myofibroblastic tumor.
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Inflammatory myofibroblastic tumor
Rare space-occupying lesion of unknown etiology that can mimic a number of benign, inflammatory
and neoplastic diseases.
Generally, benign behaviour with occasional spontaneous regression, but have been reported to recur, metastasize and undergo sarcomatous
transformation.
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Inflammatory myofibroblastic tumor
< 1% of all tumours, in adult (44y) and paediatric
populations (8y)
♂=♀
50-60% asymptomatic (cough, chest pain, fever, pneumonia
>>> haemoptysis, dyspnoea, fatigue, stridor or weight loss)
Bronchial or tracheal, central > Extrapulmonary (abdomen, retroperitoneum, pelvis, head and neck, trunk and
extremities)
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Inflammatory myofibroblastic tumor
Tipically solitary
Macroscopy: firm, circumscribed mass, white,
tan or grey cut surface
+/- necrosis
+/- calcifications.
1-15 cm (4 cm)
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Inflammatory myofibroblastic tumor Histology
SPINDLE CELLS: pale eosinophilic cytoplasm,
indistinct borders, variably tapering or plump
ovoid vesicular nuclei with well-formed nuclear
grooves, intranuclear inclusions and
multinucleation. Fascicular pattern.
Variable mitotic rate.
Nuclear atypia is generally absent or minimal.
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Inflammatory myofibroblastic tumor Histology
MIXED INFLAMMATORY BACKGROUND:
lymphocytes, plasma cells (polyclonal),
histiocytes and occasionally eosinophils and
neutrophils.
MYXOID MATRIX
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Inflammatory myofibroblastic tumor Immunohistochemistry
Positivity: • ALK ( ̴ 50%) particulary in children and
young adults. Cytoplasmic / nuclear membranous Stain pattern correlates with type of ALK rearrangement (fusion with TPM3, TPM4, CLTC, RANBP2) • Actine sm • Vimentin
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A review of the cytopathology archives at The Johns Hopkins Hospital identified 12 cases with histologically proven inflammatory pseudotumor. IPT is a rare space-occupying lesion of unknown etiology that can mimic malignancy on clinicoradiological and pathological examination. FNA of IPTs are diagnostically challenging!! Diagnostic accuracy of cytology for IPT is low (42%) Diagnosis of exclusion
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Inflammatory myofibroblastic tumor Differential diagnosis
– For spindle cell lesions:
• Sclerosing hemangioma • Fibrous solitary tumour • GIST • Benign and malignant nerve sheat tumours • Sarcomatous carcinoma • Melanoma • Sarcomas (malignant fibrous histiocytoma, leiomyosarcoma,
fibrosarcoma)
– Spindle cell less pronounced: • Plasma cell granuloma • Plasmacytoma • Lymphomas (anaplastic large cell lymphoma ALK+, Hodgkin)
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Inflammatory myofibroblastic tumor Conclusion
* IPT is a rare clinical entity of uncertain histogenesis and prognosis. * Frequent mimicker of a number of benign inflammatory and neoplastic diseases. * Spindle cell + mixed inflammatory background + myxoid matrix. Nuclear atypia and mitosis rare! * Cytologic diagnosis is possible but challenging diagnosis of exclusion! * Rearrangement of ALK gene particularly in children and young adults.
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References • Travis W.D et al. WHO Classification of Tumours of the Lung,
Pleura, Thymus and Heart. 2015: 121, 122. • Suster, Moran. Diagnostic Pathology: Thoracic. Amirsys. I (2):
192-195. • Hosler G.A., Steinberg D.M. et al. Inflammatory Pseudotumor:
A Diagnostic Dilemma in Cytopathology. Diagnostic Cytopathology, 2004; 31: 267-270.
• Lee J-C., Wu J-M, et al. Cytopathologic Features of Epithelioid Inflammatory Myofibroblastic Sarcoma With correlation of Histopathology, Immunohistochemistry, and Molecular Cytogenetic Analysis. Cancer Cytopathology, August 2015: 495-504.
• Kalpana A., Sadhana D, et al. A Rare Case of Inflammatory Myofibroblastoma of Diaphragm. Indian J Surg, June 2013; 75 (Suppl 1): S243-S246.