Salivary Gland Malignancies

8/16/2019 Salivary Gland Malignancies

1/69

Abigail C.

Schnieders

, MD

Robert P.

Zitsch

III, MD


2/69

Lumpy Lucielle

68 year old femalepresents with 6 month

history of “lump” onthe left side of her face


3/69

Mass has been slowly enlarging. No pain, nofluctuation in size. Asymptomatic otherwise.

Any other key elements of history?

What would you like to do next?

Case Presentation


4/69

PE:

Large 4cm mass of the left tail of parotid

Non compressible, firm

Facial nerve intact and symmetric bilaterally

No displacement of oropharyngeal tissue on intraoralexamination

No palpable cervical lymphadenopathyWhat else will you consider in your diagnostic work-

up?

Case Presentation


5/69

Case Presentation

Next steps?


6/69

Case Presentation

CT guided FNA

Results – neoplastic lesion

PA vs adenoid cystic


7/69

3% of all head and neck malignancies

0.9 per 100,000 US

Diverse group of malignancies

Behavior dependent on histologic type

Etiology not well understood

Possible low dose radiation exposure

Salivary Gland Malignancies

John B Sunwoo. Malignant Neoplasms of the Salivary Glands. Cummings Ch. 88


8/69

“the smaller the gland, the more likely the tumorwill be malignant”

Rate of Malignancy &

Location


9/69

Malignant neoplasm is most commonly seen withwhich gland?

1. Parotid2. Sublingual gland

3. Submandibular gland

4. Minor salivary gland

Salivary Gland Carcinoma


10/69

Malignant neoplasm is most commonly seen withwhich gland?

1. Parotid1. Although only 20-25% of parotid neoplasms are

malignant, 75-80% of salivary gland neoplasms arelocated in the parotid, thus making the total number ofmalignancies highest in this location

2. Sublingual gland

3. Submandibular gland

4. Minor salivary gland



11/69

Which histologic subtype is most commonly foundin the parotid gland?

1. Acinic Cell carcinoma2. Adenoid Cystic carcinoma

3. Adenocarcinoma

4. Mucoepidermoid carcinoma



12/69

Which histologic subtype is most commonly foundin the parotid gland?

1. Acinic Cell carcinoma2. Adenoid Cystic carcinoma

3. Adenocarcinoma


1. 80-90% of these tumors occur within the parotid gland



13/69

Which of the following subtypes is most commonlyfound in the submandibular and minor salivary

glands?1. Acinic Cell carcinoma

2. Adenoid Cystic carcinoma


4. Squamous Cell carcinoma



14/69

Which of the following subtypes is most commonlyfound in the submandibular and minor salivary

glands?1. Acinic Cell carcinoma

2. Adenoid Cystic carcinoma

1. 2/3 of these tumors arise from minor salivary glands

3. Mucoepidermoid carcinoma4. Squamous Cell carcinoma



15/69

Asymptomatic Mass Range from indolent to rapidly growing

Pain Can be associated with infection, cystic degeneration

May indicate invasion of perineural tissue

Spiro et al

2807 patients

10% - pain 10% - CN VII paralysis

Episodic swelling Gland obstruction

Clinical Presentation

Spiro RH. Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg. 1986;8(3):177-184.


16/69

Parapharyngeal Space

InvolvementMass on oral

examination

Alterations in speechand swallow due tomass effect

70-80% of

parapharyngeal spacetumors are benign

Parapharyngeal Space Tumors Author: Christine G Gourin, MD, FACS; Chief Editor: Arlen D Meyers

l d l d


17/69

Prestyloid vs. Post-styloidspace

Parapharyngeal space divided intocompartments by the fascia of thetensor veli palatini

The prestyloid compartmentcontains: retromandibular portion of the

deep lobe of the parotid gland,adipose tissue, and lymph nodesassociated with the parotid gland

The poststyloid compartmentcontains: the internal carotid artery, the

internal jugular vein, CNs IX- XII,the sympathetic chain, and lymphnodes.

Management of Tumors of the Parapharyngeal Space. Ricardo L. Carrau, MD, Jonas T. Johnson, MD, Eugene N. Myers, MD |May 1, 1997. Department of Otolaryngology,University of Pittsburgh Medical Center, Pennsylvania


18/69

Reserve cell theory

Neoplasms arise from stem cells of the salivary ductsystem

Multicellular theory

Neoplasms arise from differentiated cells along the gland

Type of neoplasm dependent on stage of differentiationof the cell at the time of neoplastic transformation Intercalated duct

Adenoid cystic & acinic cell carcinoma

Excretory duct

Mucoepidermoid, squamous cell, ductal carcinoma

Pathogenesis


19/69

Pathogenesis


20/69

WHO Classification


21/69

Classification


22/69

Prevalence by Histologic Subtype


23/69

Mucoepidermoid carcinoma

Name that tumor


24/69

Most common salivary gland malignancy

80-90% occur in parotid Second most common malignancy of the SMG

Female predominance

Mean age of 45

Also the most common salivary gland cancer inpediatric population

Mucoepidermoid Carcinoma


25/69


Grossly appear as bluish cyst

May disguise as mucocele

Histologically: hallmark ismixed population of cells

Mucous

Epithelial (squamoid)

Intermediate

Clinical behavior andtreatment based on grade


26/69


Increase in grade = loss ofcystic formations and moresolid nests of tumors

Several different gradingsystems

Designed to identify tumorsthat develop progressivedisease

Brandwein et al Refined grading system

such that low gradetumors did not showtendency to metastasize


27/69


Low grade Cystic areas with mucin High proportion of mucous cells to

epidermoid cells Well-circumscribed, pushing

margins Capable of local invasion and

metastasis 5-yr survival = 70%

High grade Solid

Low proportion of mucous cells toepidermoid cells Differentiation from scca

Characterized by invasion ofadjacent normal structures,atypical mitoses, perineuralinvasion, lymph node metastases

5-yr survival = 47%


28/69

Adenoid cystic carcinoma Bonus Points: which histologic subtype? cribriform

Name that tumor


29/69

Biologically and clinically distinct subtype of

salivary gland carcinoma 10% of salivary gland neoplasms

Second most common malignancy of parotid

M=F

Peak incidence between 50-60

Adenoid Cystic Carcinoma


30/69

“Contradictory clinical course”

Slow growing

Infiltrative

Multiple recurrences over a protracted course

Frequent distant metastases



31/69

Grossly: solid, light tan, firm, well circumscribed, butunencapsulated



32/69


Histologically:

Differentiate toward

cells of normal salivarygland acini

Infiltrates surroundingtissues

Characterized by

basaloid epithelial nestsin a hyaline stroma

Perineural invasion is atypical feature


33/69


Grade I

Tubular ACC Small tubule-like

structures withepithelial lining sittingin a pink, hyalinizedand hypocellularstroma

35%


34/69

Adenoid Cystic Grade II

Cribriform “Swiss cheese” pattern of

vacuolated areasNests of basaloid cells

arranged around gland-like spaces

Central spaces look likeglandular lumina but arereally extracellular

cavities containingground substance andmyxoid materialproduced by tumor cells

44%


35/69


Grade III

SolidSolid sheets/ nests

of basaloid cellsno gland-like

structuresno defined

architecture

21%


36/69

Perineural invasion

Identified in 70-75% of cases

Typically associated with a poorer prognosis



37/69

Persson et al

Recent identification of tumor specific translocation in

six patients t(6;9) (q22-23;p23-24)

Fuses MYB oncogene to transcription factor geneNF1B

Leads to activation of MYB targets Apoptosis, cell cycle control, cell growth



38/69

Name that Tumor!

Hints:

2 cell types

Serous acinar Clear cells

4 histologic patterns

Acinic cell carcinoma


39/69

Name that Tumor!

Hints:

Ductal component

Myoepithelial cells

A:

Epithelial-myoepithelial


40/69

FNA

Among tumors of the head and neck, FNA of the salivarygland are considered to have the highest rate of error

College of American Pathologists Inter-laboratoryComparison Program

5 year review of data (6249 cases) 73% sensitivity False negatives: Lymphoma, Acinic cell, low grade mucoepidermoid, Adenoid

cystic

91% specificity False postive: Adenoid cystic Monomorphic adenoma/ Pleomorphic adenoma

LymphomaWarthins

Batsakis JG, Sneige N, El-Naggar AK. Fine-needle aspiration of salivary glands: its utility and tissue effects. Ann Otol Rhinol Laryngol 1992;101:185


41/69

Debate over cost effectiveness Ultimate surgical removal in most cases May impact necessity for intraoperative frozen section analysis Extent of tumor spread, margins, confirming diagnosis

Advantages Potential to obtain definitive diagnosis Direction of management Preoperative patient counseling

Disadvantages Hemorrhage/ infarction may obscure final diagnosis Delay in definitive treatment Surgical excision still needed for definitive diagnosis

FNA

Batsakis JG, Sneige N, El-Naggar AK. Fine-needle aspiration of salivary glands: its utility and tissue effects. Ann Otol Rhinol Laryngol 1992;101:185


42/69

Which modalities are best for imaging salivary glandmasses?

US

CT

MRI

PET

Imaging


43/69

Ultrasound

US cannot definitivelydetermine malignancy

Malignant features: Irregular shape/ borders

Blurred margins

Hypoechoic structure

Intraglandular nodes

Many benign neoplasmscan also have thesefeatures


44/69

CT

The periparotid fat stripseparating the deep lobe of theparotid gland from theparapharyngeal space is animportant anatomic landmark

Allows for the differentiationof deep lobe parotid tumorsinvolving the parapharyngealspace from tumors that arise

from ectopic salivary glandtissue in the parapharyngealspace.

MRI


45/69

MRI

Benign and malignant

lesions aredistinguishable on T1 Separation from fatty

parenchyma Sorn and Biller 35 tumors examined by MRI

Benign tumors = low T1 andhigh T2 with well definedmargins

Malignant lesions = low T1and T2 signal with poorlydefined margins

Freling and colleagues 116 patients with parotid

masses No correlation between

malignancy and signalintensity or margin analysis

PET


46/69

Potential role for staging and management in salivary

gland carcinomas

Kim et al Retrospective review of 55 patients

Compared PET/CT and CT/MRI

Sensitivity/ specificity for PET – 96%/92%

Sensitivity/ specificity for MRI/CT – 54%/83%

Tumor grade was unassociated with sensitivity of the test

Identified the need for additional surgery in 47% ofpatients

PET

Roh JL, Ryu CH, Choi SH, et al. Clinical utility of 18F-FDG PET for patients with salivary gland malignancies. J Nucl Med 2007;

Razfar A, Heron DE, Branstettar BF, et al. Positron emission tomography–computed tomography adds to the management of salivary glandmalignancies.Laryngoscope 2010; 120:734–738.

St i


47/69

Staging


48/69

Mainstay of treatment is surgery

Parotidectomy Lateral lobe tumors can be treated with superficial

parotidectomy

Partial deep lobe resection can be performed to achievenegative margins

Total parotidectomy indicated for High grade malignant tumors with high risk for metastasis

Any parotid lesion with intraglandular or cervical nodemetastases

Any lesion within the deep lobe itself

Surgical Treatment


49/69

SMG

Gland excision with level Ib dissection recommended

Sublingual Wide local excision with level I dissection

Reconstruction with STSG or free tissue transfer

MSG

Most frequent location palate

Partial or total maxillectomy

Surgical Treatment


50/69

Management of Neck

Spiro RH. Management of malignant tumors of the salivary glands. Oncol 1998;12(5):671. (Review of treatment guidelines for malignant

neoplasms of the salivary glands.)


51/69

Management of the Neck

Management of the N0 neck Neck dissection recommended

with

Tumors >4cm

High grade histology

Management of the N+ neck

Ipsilateral MRND for clinicallyor radiographically positive

nodes Incidence of multilevel node

involvement

R di ti Th


52/69

Radiation Therapy

Adjuvant radiation therapy improves local control

T3/T4

High grade Positive nodes

Perineural involvement

Close or positive surgical margin

Bone, cartilage, muscle involvement Recurrent disease

R di ti Th


53/69

Neutron beam radiation

Higher rates of locoregional control compared to

conventional radiation Advanced stage

Recurrent disease

Incomplete resection

Higher degree of tumor destruction with less toxicityto surrounding tissue

Particularly good for adenoid cystic

Radiation Therapy

Prott FJ, Micke O, Haverkamp U et al. Results of fast neutron therapy of adenoid cystic carcinoma of the salivary glands. Anticancer Res 2000;20(5C):3743. (The University of Munster experiencewith neutron-beam radiotherapy and adenoid cystic carcinoma.)

Douglas JG et al. Treatment of salivary gland neoplasms with fast neutron radiotherapy .Arch OtolaryngolHead Neck Surg 2003;129 (9):944. (The University of Washington experience with andtheir evaluation of the efficacy of neutron-beam radiotherapy for adenoid cystic carcinoma.


54/69

Chen et al

Retrospective analysis of 140 patients with ACC

Omission of postoperative RT independentlypredicted local recurrence

hazard ratio of 5.82

Identified certain features of tumors wherebypostoperative radiation therapy is useful controllinglocoregional recurrence

Advanced stage tumors, presence of positive margins,high grade tumors, neural/ bone involvement

Radiation Therapy

Chen AM. Adenoid Cystic carcinoma of the head and neck treated by surgery with or without postoperative radiationtherapy: prognostic features of recurrence. Int J Radiat Oncol Biol Phys 2006; 66:152-9


55/69

Dutch Head and Neck Oncology Cooperative Group Terhaard et al

Retrospective multivariate analysis of 565 patients Surgery alone = relative risk of local recurrence of 9.7

compared with those patients treated by surgery andpostoperative RT

Improved regional control in N+ neck 86%vs 62%

No effect on development of distant metastases or overallsurvival

Radiation Therapy

Terhaard CH. The role of radiotherapy in the treatment of malignant salivary gland tumors. Int J Radiol Biol Phys 2005; 61:103-111


56/69

Terhaard et al 386/498 patients received adjuvant RT

10 year local control rates:

Same results were not observed for T1/T2 tumors

T1 – 95% vs 83%

T2 – 91% vs 88%

Adjuvant Radiotherapy

Adjuvant RT Surgery only

T3/T4 tumors 84% 18%

Close margins 95% 55%

Positive margins 82% 44%

Bone invasion 86% 54%

P


57/69

Armstrong et al Retrospective matched pair analysis

Postoperative RT improved local control in stageIII/IV 5 year local control rates Surgery + RT = 51%

Surgery alone = 17%

5 year determinate survival rates 51.2% and 9.5%

No difference in outcomes between two treatmentgroups in patients with stage I and II

Radiation Therapy

Armstrong JG. Malignant tumors of the major salivary glands. A matched pair analysis of the role of combined surgery andpostoperative radiotherapy. Arch Otolarynol Head Neck Surg. 1990;116:290-3


58/69

Matsuba et al

Study of high grade malignancies of parotid

5 year local control rates 70% with post op RT

20% without

Radiation Therapy

d d h


59/69

Adjuvant Radiation Therapy


60/69

Typically limited to palliative

Partial responses in 50%

Pain control

Paclitaxel

Chemotherapy alone does not improve survival rates

ChemoRT increases local control and

Chemotherapy


61/69

Mostly based on small patient series, often withmultiple histologic subtypes within studies

Eastern Cooperative Oncology Group Phase II trial

Single agent paclitaxel in 45 patients

8/31 with mucoepidermoid or adenocarcinoma had

partial response 0/14 of adenoid cystic carcinoma showed response

Chemotherapy

Gilbert J. Phase II trial of taxol in salivary gland malignancies: a trial of the Eastern Cooperative Oncology Group. HeadNeck 2006; 28 (3):197-204


62/69

Concurrent chemoRT

After primary surgical resection in high risk patients

After surgical resection for recurrence In inoperable patients

Chemo Radiation

Pederson AW, HarafDJ, Blair EA, et al. Chemoreirradiationfor recurrent salivary gland malignancies. Radiother Oncol 2010; 95:308–311.Tanvetyanon T, Qin D, Padhya T, et al. Outcomes of postoperativeconcurrent chemoradiotherapy for locally advanced major salivary gland carcinoma. Arch Otolaryngol Head Neck Surg

2009; 135:687–692.Katori H, Tsukuda M. Concurrent chemoradiotherapy with cyclophosphamide, pirarubicin, and cisplatin for patients with locally advanced salivary gland carcinoma. Acta Otolaryngol 2006;126:1309–1314.


63/69

Tanvetyanon et al 24 patients with locally advanced major salivary gland

carcinoma 12 treated with postoperative RT 12 treated with postoperative concurrent chemoradiotherapy

All but 1 patient had stage III or IV disease Close or positive margins noted in 83% Median radiation dose was 63 Gy Platinum based regimens were used in chemoRT arm

Overall 3 year survival Radiation alone = 44% Chemoradiation = 83% P= 0.05

ChemoRT

Tanvetyanon T. Outcomes of Postoperative Concurrent Chemoradiotherapy for Locally Advanced Major Salivary Gland Carcinoma. Arch Otolaryngology HeadNeck Surg 2009; 135 (7): 687-692

Post Operative ChemoRT


64/69

Post-Operative ChemoRT

Tanvetyanon T. Outcomes of Postoperative Concurrent Chemoradiotherapyfor Locally Advanced Major Salivary Gland Carcinoma. Arch

Otolaryngology Head Neck Surg 2009; 135 (7): 687-692


65/69

Management

Head Neck Pathol 2009 March; 3(1) 69-77


66/69

Recent interest in molecular targeting of salivary gland

malignancies Molecular markers

EGFR Overexpression in all histologic subtypes Lapatinib (tyrosine kinase inhibitor of EGRF and HER2)

Phase II study showed disease stability in 36%

HER2 Ductal carcinoma

C-kit Adenoid cystic Imatinib (c-kit inhibitor)

Although there is overexpression of these molecular markers,the rates of true genetic mutation is much lower

Molecular Targeting

Papaspyrou G, Hoch S, Rinaldo A, et al. Chemotherapy and targeted therapy in adenoid cystic carcinoma of the head and neck: a review. Head Neck 2010Locati LD, Perrone F, Losa M, et al. Treatment relevant target immunophenotyping of 139 salivary gland carcinomas (SGCs). Oral Oncol2009; 45:986–990.


67/69

Radiation Therapy Oncology Group

Recently opened a phase II randomized trial

Comparing radiation and concurrent cisplatin withradiation alone in high risk patients after surgicalresection

ChemoRT

Prognostic Variables


68/69

Prognostic Variables

Overall 10-year disease freesurvival rate of patients withsalivary gland malignancies~47-74%


69/69

Pederson DJ, Blair EA, et al. Chemoreirradiation for recurrent salivary gland malignancies. Radiother Oncol 2010;

95:308–311. Tanvetyanon T, Qin D, Padhya T, et al. Outcomes of postoperative concurrent chemoradiotherapy for locally

advanced major salivary gland carcinoma. Arch Otolaryngol Head Neck Surg 2009; 135:687–692. Katori H, Tsukuda M. Concurrent chemoradiotherapy with cyclophosphamide, pirarubicin, and cisplatin for

patients with locally advanced salivary gland carcinoma. Acta Otolaryngol 2006; 126:1309–1314. Papaspyrou G, Hoch S, Rinaldo A, et al. Chemotherapy and targeted therapy in adenoid cystic carcinoma of the

head and neck: a review. Head Neck 2010 Locati LD, Perrone F, Losa M, et al. Treatment relevant target immunophenotyping of 139 salivary gland

carcinomas (SGCs). Oral Oncol 2009; 45:986–990 Roh JL, Ryu CH, Choi SH, et al. Clinical utility of 18F-FDG PET for patients with salivary gland malignancies. J Nucl

Med 2007; Razfar A, Heron DE, Branstettar BF, et al. Positron emission tomography–computed tomography adds to the

management of salivary gland malignancies.Laryngoscope 2010; 120:734–738

• Batsakis JG, Sneige N, El-Naggar AK. Fine-needle aspiration of salivary glands:its utility and tissue effects. Ann Otol Rhinol Laryngol 1992;101:185\

• Cummings . Chapter 88• Bailyes. Chapter 109

References

Documents

Salivary Gland Malignancies