Salivary gland Workshop Trondheim 31th may 2012 Peter Jebsen cytopathologist Oslo University Hospital Rikshospitalet Anna Bofin ass. Professor St. Olavs Hospital, Trondheim
Drying artifacts Lymfocytes and ciliated epithelium PAP x 400
Lymfocytes with lytic changes (above) and without artifacts (right). DQ x400
WHO histological classification of salivary gland tumors 2005 Benign epithelial tumors Pleomorhic adenoma Myoepithelioma Basal cell adenoma Warthins tumor Canalicular adenoma Lymphadenoma, sebaceous/non-sebaceous Ductal papilloma inverted papilloma - intraductal papilloma - sialadenoma papilliferum Cystadenoma
Pleomorphic adenoma Def WHO 2005 Pleomorphic adenoma is a tumor of variable encapsulation characterized microscopically by architectural rather than cellular pleomorphism. Epithelial and modified myoepithelial elements intermingle most commonly with tissue of mucoid, myxoid or chondroid appearance. Cytology -fibrillary chondromyxoid ground substance - spindle shaped mesenchymal cells seen mainly in stromal matrix - epithelial cells single and in poorly cohesive clusters and sheets - regular ovoid nuclei with bland nuclear chromatin and well defined cytoplasm
Salivary gland From biopsy archive: Cytology + M89400 + 2008 +2009: 2008: FNAC 59 cases from 57 patients 2009: FNAC 47 cases from 45 patients Total 106 cases 102 patients Follow up: 65 Parotid PA (6 patients with recurrence) 25 No surgical follow up 5 Parafaryngeal tumors (3 PA, 1 Chordoma, 1 no surgery) 4 Myoepithelioma (2 previous surgery for PA same location) 1 Basal cell adenoma 2 Small salivary gland tumors (1 PA, 1 Adenoma NOS)
Cg 1745/09
CHORDOMA CK EMA S100
Cytology from Lillehammer small county lab Probably epithelial tumor with myxoid stromal komponent consider pleomorhic adenoma (FNAC from tumor in pharynx). NB! We have also considered the possibility of a chordoma which may present a similar microscopic picture. Our diagnosis should be related to radiologic findings. Other mesenchymal lesion is not excluded( ekstraskeletal myxoid chondrosarkoma) but we consider this probability more unlikely. From medical records: Cytology suggest pleomorphic adenoma but radiology is consisten with chordoma with a large tumor in the area of C2.
Parapharyngeal chordoma: A diagnostic challenge and potential mimic of pleomorphic adenoma on fine-needle aspiration cytology. Castro M et al: Diagn. Cytopathol 2011 Nov 18. The above mentioned paper is the first publication on chordoma mimicking pleomorphic adenoma. but patient had previously been treated for chordoma
Myoepithelioma
Myoepithelial cells Can look like other cells Plasmacytoid Spindle celle Epitheloid Clear cell Myoepithelial immun markers: P63, ck5/6 (s 100, SMA)
Female 40 years old. Tumor anterior to right ear for some years. X40 Cg 390/09 Cellgroups without pink fibromyxoid stroma
Warthins tumor Def: A tumor composed of glandular and often cystic structures lined by columnar eosinophilic or oncocytic cells. The stroma contains a variable amount of lymphoid tissue with germinal centres. (WHO 2005) ------ Probably related to tobacco smoking Look for 3 components in smears: -oxyfilic epithelial cells -cystic component with debris and macrophages -lymphoid cells Our experience: Could be a difficult diagnosis unless all 3 components are clearly present. More false positive diagnosis then in PA! and more non-conclusive specimen
Cg 09 538
Cg 11 188
From pathology archive 2008-2011 M 85610 Warthins tumor cyt and hist Cytology 2008 21 cases 21 patients 2009 18 cases 17 patients 2010 30 cases 25 patients 2011 35 cases 29 patients Total 104 cases 94 patients 15 surgical follow up: Warthins tumor
The other way round.ie: What have Warthins tumor been called on preop FNAC? Biopsy Cytology 2008 11 cases 5 Warthin 4 cystic lesions (1 FN Warthin) (1 incidental finding no cyt) 2009 2 cases 1 Warthin 1 suspicious sq cells (other lab) 2010 5 cases 2 Warthin 1 non-representative 1 cyst /FN Warthin) 1 mal. cells (FP!) 2011 12 cases 7 Warthin 3 cystic lesions (1 FN Warthin) 1 susp sq cells 1 non-diagn Total 30 cases 15 Warthin 9 cysts (3 FN Warthin) 3 susp/malignant 2 non-diagn 1 no cyt
Male 68 years old. Tumor caudal to right parotid gland. Metastases or salivary gland tumor? Cg11 826
More single atypical squamous cells
The patient underwent radio-chemo therapy and neck dissection Neck dissection with Warthins tumor and a small area with macrophage reaction as the only findings. Notification of possibly wrong cytologic diagnosis with adverse treatment effect was sent.
Female 80 years. Tumor left side of neck and a pulmonary tumor with unknown diagnosis.
CT-guided fnac (other hospital) showed non-small cell carcinoma with dissimilar cells compared to cells from neck and neck tumor was removed. Other constituents of cellmaterial with onkocytic differentiation clue to Warthins tumor? Cg09 2039
Onkocytoma DEF: Benign tumors composed of large, polygonal epithelial cells with prominent eosinophilic cytoplasm that is due to accumulation of atypical mitochondria.
Male 57 years- for 2 years slowly growing tumor in left parotid gland -Oncocytic cells no cytoplasmic granularity -Prominent dissosiation- is also seen in Acinic Cell Carcinoma
Cg09 904 Female 65 years Slow growing tumor in right parotid gland
Onkocytoma. Note fibrous capsule Dd: Dominant nodule in oncocytic hyperplasia
Nodular oncocytic metaplasia with dominant nodulus. Right picture shows multiple foci of microscopic metaplastic nodules in macroscopic tumorfree area(he x20) The metaplastic cells often shows clear cell differentiation in this condition Bg 10 3085
WHO histological classification of salivary gland tumors 2005 Malignant epithelial tumors Acinic Cell Carcinoma Mucoepidermoid carcinoma Adenoid cystic carcinoma Epithelial-myoepithelial carcinoma Clear cell carcinoma NOS Basal cell adenocarcinoma Sebaceous carcinoma Cystadenocarcinoma Salivary duct carcinoma Myoepithelial carcinoma Squamous cell carcinoma Small cell carcinoma And 12 other carcinoma types (total 24 entities) Malignant lymphomas Metastases!
Acinic Cell Carcinoma Def: (WHO) Acinic Cell Carcinoma is a malignant epithelial neoplasm of salivary glands in which at least some of the neoplastic cells demonstrate serous acinar cell differentiation, which is characterized by cytoplasmic zymogen secretory granules. Salivary ductal cells are also a component of this neoplasm. Histogenesis Most investigators consider tumor origin probably from neoplastic transformation of terminal ductal cells. However it has been shown that normal serous acinar cells undergo mitotic division and some acc could arise from transformation of these cells (WHO H&N 2003)
Above: Normal parotid gland x100 Right: ACC
-ACC with prominent lymphoid component-dd metastases to lymph node. - This phenomenon also observed in some Mucoepidermoid carcinomas
Adenoid cystic carcinoma Def (WHO) Adenoid cystic carcinoma (AdCC) is a basaloid tumor consisting of epithelial and myoepithelial cells in variable morphologic configurations (tubula, cribriform and solid) It has a relentless clinical course and ususally a fatal outcome. Diff diagnosis (according to WHO) Basal cell adenoma Basal cell adenocarcinoma Epithelial-myoepithelial carcinoma Cellular pleomorphic adenoma Polymorphous lowgrade adenocarcinoma
Female 30 years old. Tumor in right submandibular gland Cg1940/10
Immunomarkers useful for subtyping -androgen receptor and AP15 - Salivary duct carcinoma cd 117 (c-kit) - Adenoid cystic carcinoma -Bcl2 basal cell adenoma - ck5/6 and ck 7 demonstrates epithelial/myoepithelial pattern -. Origin of metastases
The ENT-surgeons algoritm for treating salivary gland tumors 1: Benign tumors - surgery with free margins (< 0.5 millimeter will do) 2: Lowgrade malignant tumors surgery with free margins Generally-specify shortest tumorfree margin in millimeters, 3: High-grade malignant tumors- Salivary duct carcinoma, dedifferentiated salivary gland carcinomas, high-grade adeno carcinoma NOS. Surgery with free margins + radiotherapy Aim for the cytologist according to the ENT-surgeon: To classify the tumor according to one of the above mentioned categorys
How sure can we be about the correctness of our cytologic diagnosis? -Pleomorphic adenoma is almost always correctly recognized, (myoepithelioma, basalcell adenoma) and almost never mistaken for malignant lesions. -Warthins tumor- the diagnosis is easy in typical cases BUT regular false positive diagnosis for atypical squamous lesion/metastases from squamous cell carcinoma occur -Be careful- if no primary scc could be found -Consider biopsy if irregular/atypical squamous cells are found in places were parotid gland origin could not be excluded -Adequate information about tumor location is important (lymph node vs salivary gland)
How is the reproducibility of the malignant categories? Low-grade lesions- acinic cell carcinoma and the well differentiated adenoid cystic carcinoma are mostly correct diagnosed. Note many different entities according to WHO-classification, many are rarely seen and many of the lesions have overlapping features ie: low reproducibility of the singel entity with no consequence for patient-treatment according to preop. algoritm. High-grade lesions highly atypical and no difficulty in recognizing malignant cells. Parotid primary usually salivary duct carcinoma or adenocarinoma NOS. Note that metastases in parotid gland is just as frequent as high-grade primary carcinomas. Squamous cell carcinoma most scc are metastases. On cytology consider primary scc as an exclusion diagnosis
Recommendations ( = Useful cytologic categories according to PJ) -pleomorphic adenoma -Warthins tumor These 2 diagnosis make up approx 70% of all lesions -acinic cell carcinoma -adenoid cystic carcinoma -lowgrade carcinoma NOS -high grade adenocarcinoma -metastases
From AFIP: Tumors of Salivary Gland, serie 4
Myoepithelial cells Can look like other cells Plasmacytoid Spindle cells Epitheloid Clear cell Myoepithelial immun markers: P63, ck5/6 (s 100, SMA)