Case of the month December 2017

Dre Ana Barrigón Benítez Institut universitaire de pathologie, Lausanne

Clinical history

30 years-old male, presenting with a right

lower pulmonary mass.

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.

Bronchial aspiration

PAP, 20x. Spindle cells in a myxoid stroma.

PAP, 40x.

Granuloma?

PAP, 200x.

Bronchial aspiration

PAP 400x. Spindle cells with elongated nuclei (sometimes binucleated) and prominent nucleolus.

Bronchial aspiration

PAP 400x. Mild irregularity of nuclear contours. Intranuclear inclusions (arrow). Mixed inflammatory infiltrate.

Giant cell

PAP, 400x. Intranuclear inclusions (arrow).

PAP, 400x.

PAP, 200x.

PAP, 400x.

PAP, 400x.

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.

H&E, 400x Cell-block

H&E, 400x Cell-block

H&E, 400x

Cell-block

H&E, 400x

Cell-block

ALK: cytoplasmic and nuclear staining, 400x

Immunocytochemistry Cell-block

Immunocytochemistry

ALK: cytoplasmic and nuclear staining, 400x

Immunocytochemistry

• Cells are positive for:

– Vimentine & ALK (strong).

– AML, EMA et focally S100.

– Calponine (weak).

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)

ALK rearrengement – break-apart FISH

Biopsy

Courtesy dr. Letovanec, dr. Bisig

Cytologic Diagnostic

Mesenchymal tumor, ALK-positive, consistent with

inflammatory myofibroblastic tumor.

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.

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)

Inflammatory myofibroblastic tumor

Tipically solitary

Macroscopy: firm, circumscribed mass, white,

tan or grey cut surface

+/- necrosis

+/- calcifications.

1-15 cm (4 cm)

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.

Inflammatory myofibroblastic tumor Histology

MIXED INFLAMMATORY BACKGROUND:

lymphocytes, plasma cells (polyclonal),

histiocytes and occasionally eosinophils and

neutrophils.

MYXOID MATRIX

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

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

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)

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.

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.