Salivary Tumors

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Salivary Tumors
Leon Barnes, M.D. University of Pittsburgh
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In-Situ and Minimally Invasive Carcinoma ex
Pleomorphic Adenoma
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Pleomorphic Adenomas

• APA PA CPA
• Chondroma 5 Basal cell
  adenoma
• Myxoma Myoepithelioma
• 
  Malignant
• Ca ex PA Carsar
  MZPA ?Sa ex PA
• CIS
• MIC
• IC

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In-situ Carcinoma( non-invasive, intracapsular)
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Ki-67
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P 53
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Her-2
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Minimally Invasive Carcinoma
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S-100
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C
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C
C
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Carcinoma-in-situ ExPleomorphic Adenoma

• Of 47 carcinomas ex pleomorphic adenoma reviewed
• by LiVolsi and Perzin, 6 (13) were in-situ.
• None developed local recurrence or metastasis
• following complete excision.
• Must thoroughly section tumor to rule out
  invasion.
• Li Volsi VA, Perzin KH, Cancer 392209, 1977.

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Minimally Invasive CA ex PA

• Tortoledo1984
• 8 mm or less, none DOD
• More than 6 mm, 70.5 local recurrence
• Less than 6 mm, 16.5 local recurrence
• Lewis2002
• 4 patients with invasion of 5 mm
• 2 no progression, 2 DOD
• Cautious prognosis less than 5 mm.

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Encapsulated and minimally invasive CA ex PA

• 12 cases of encapsulated or minimally invasive CA
  ex PA (1.5 mm or less)
• Mean 1.8 cm (range 0.8-3.5 cm)
• 5 aneuploid and 2 diploid no predictive value
• No recurrences or metastasis in 11 cases at mean
  follow-up of 4.2 yrs. (range 15 mos - 13 yrs.)
• Brandwein M, et al, Oral Surg 81655, 1996

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2005 WHO Classification

• Carcinoma ex pleomorphic adenoma
• Non-invasive
• Minimally invasive ( 1.5 mm or less )
• Invasive ( more than 1.5 mm )

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Mets in CIS ex PA

• Author N Mets (follow up)
• LiVolsi 6 0 ( unknown)
• Brandwein 4 0 ( 3-13 yr)
• Lewis 4 0 ( 14 mos-17
  yr)
• Felix 1 1 (
  presented )
• Ihrler 10 0 ( unknown)
• Di Palma 11 0 ( 1-6 yr )
• 36 1 (
  2 )

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Mets in CIS-MIC Ca ex PA

• 12 cases of CIS-MIC
• 30 months median follow-up
• 3 of 12 (25) developed mets vs 8 of 17 (47)
  for greater than 1.5 mm
• 1 MIC patient died of disease
• Katabi N, et al. Mod Pathol 21(suppl 1)
  2008 237A

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Polymorphous Low-Grade Adenocarcinoma
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PLGA

• Occurs almost exclusively in the oral cavity.
• In some series, it represents the second most
  common malignant salivary gland tumor of the oral
  cavity, accounting for 26 of all malignant
  tumors in this region.
• Exceeded in frequency only by mucoepidermoid
  carcinoma which accounts for 36 of all malignant
  intraoral salivary tumors.

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PLGA

• 2 times more common in women
• Average age 50-60 years (range 12-94)
• Slowly growing, slightly elevated, round to oval
  mass. Sometimes polypoid.
• Usually between 1-6 cm, tan or white on sectioning

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PLGA- 337 cases

• Palate 57
• Buccal mucosa 16
• Lip 13
• Alveolar mucosa 4
• Retromolar trigone 3
• Tongue 2
• Floor of mouth 1
• Other sites 9

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PLGA

• Infiltrative growth, multiple patterns of growth,
  and cytologic uniformity
• Solid Rare mitoses
• Glandular No necrosis
• Cribriform Perineural invasion
• Trabecular Calcification
• Cystic
• Papillary

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C-KIT
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CALP
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PLGA

• Complete local excision treatment of choice
• 10-30 incidence of local recurrence
• 5-10 metastasize to cervical lymph nodes
• Distant metastasis uncommon
• More than focal papillary pattern associated
  with increased lymph node mets ( 6/17 35)

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PLGA Differential Diagnosis

• Pleomorphic adenoma
• Adenoid cystic carcinoma
• Low grade papillary adenocarcinoma

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Pleomorphic Adenoma
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P63
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Tumor GFAP

• PA
• PLGA -

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Polymorphous L-G AdenocarcinomavsAdenoid
Cystic Carcinoma
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ACC
C-KIT
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PLGA vs ACC

• Stain PLGA ACC
• KI-67 lt5 gt20
• Bcl-2 Weak-Mod Strong
• S-100 Strong Weak
• Vargas H, et al. Appl Immunohistochem 58-16,
  1997

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PLGA vs ACC

• Feature PLGA ACC
• Cribriform /-
  
• Papillary
  -
• Cysts
  -
• Calcific deposits -

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Low Grade Papillary Adenocarcinoma
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Salivary Duct Carcinoma
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Salivary Duct Carcinoma (N104)

• Age 22-91 years (most over 50)
• Gender 78 M, 22 F
• Sites Parotid 91
• Submandibular 9
• Stensens duct 1
• Buccal mucosa 1
• Tongue 1
• Palate 1

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P63
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Salivary Duct Carcinoma - Variants

• In-situ (intraductal)
• Sarcomatoid
• Mucin-rich
• Micropapillary

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Salivary Duct Carcinoma (N104)

• Size several mm -7 cm
• Perineural invasion 60
• Vascular invasion 31
• Local recurrence 33
• Lymph node mets 59
• Distant mets 46
• Dead of disease 65 (usually in 4 yrs)
• Barnes L, et al. Oral Surg Oral Med Oral Pathol
  7864, 1994

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Salivary Duct Carcinoma Hormonal Status

• Reference Total Cases ER
  PR AR
• Dimery 1 1 ND ND
• Delgado 11 0 ND ND
• Barnes 12 1 0 ND
• Kay 40 0 9 33
• Ockner 17 0 3
  ND
• Nasser 6 0 0 6
• Hoang 28 ND ND 20
• Kapadia 12 0 0 11
• Total 127 2/99 12/87 70/86
• (100) (2) (14) (81)

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Salivary Duct Carcinoma and HER 2 - neu

• 1. 25- 88 positive
• 2. Skalova
• IPEX 8 of 11 were 3, 3 of 11 were 1 to 2
• FISH 4 of 10 showed gene amplification
• No difference in prognosis between
  amplified and non-amplified tumors
• Skalova A, et al Histopathology 42248, 2003

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SDC Differential Diagnosis

• Metastatic breast carcinoma
• Metastatic prostatic carcinoma
• Polymorphous low-grade adenocarcinoma
• Oncocytic adenocarcinoma
• Mucoepidermoid carcinoma
• Adenocarcinoma, NOS

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Breast Metastatic to Parotid Gland

• AFIP Literature
• Total 400 785
• Number 8 19
• 2 2.4
• Gnepp DR, Surg Pathol of Salivary Glands

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Sclerosing Polycystic Adenosis
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SPA

• First described in 1996 by Smith et al.
• Generally regarded as salivary equivalent of
  fibrocystic diseasesclerosing adenosis of
  breast
• Few cases have shown ductal atypia/dysplasia,
  carcinoma-in-situ or clonality raising
  possibility that it may even be a neoplasm.

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SPA

• Only about 40 cases in literature.
• All age groups-- range 9-84 yrs ( ave 41).
• Slightly more common in females ( 58).
• Most present with asymptomatic mass of months to
  years duration. Few associated with pain.

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SPA---35 Cases

• Site Number ()
• Parotid 28
  (80)
• Submandibular 3 (
  9)
• Minor 4
  ( 11)
• (palate, fom, buccal)

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SPA

• 0.3 to 6.0 cms.
• Firm, rubbery, sharply demarcated, occassionally
  multinodular.
• Glistening pale gray cut surface, cystic, often
  with interspersed yellow foci.

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SPA

• Well demarcated, nonencapsulated with peripheral
  rim of normal salivary tissue.
• Matrix is fibrous often with interspersed adipose
  tissue.
• Well to poorly defined lobular proliferation of
  epithelial cells with both ductal and acinar
  differentiation.

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SPA

• Acini may contain prominent, eosinophilic zymogen
  granules.
• Multifocal areas of adenosis.
• Ducts often dilated or cystic and lined by
  epithelium that varies from atrophic to
  hyperplastic to cribriform.

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SPA

• Some ductal cells may be apocrine, mucinous,
  squamoid, or sebaceous.
• Infrequently ductal cells may exhibit
  atypia/dysplaia or carcinoma-in-situ.
• Background of chronic inflammation

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Calponin
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Calponin
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Cam 5.2
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Laminin
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Laminin
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P 63
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ER
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ER
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ER
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P 53
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CD 34
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SPA

• Simple surgical excision.
• 10-20 may recur, usually after an interval of 4
  or more years.
• Histology of recurrent tumor similar to original.
  
• No patient thus far has developed metastasis or
  died of disease.

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SPA

• Polycystic (dysgenetic) disease
• Chronic sclerosing sialadenitis (Kuttner
  tumor)
• Carcinoma

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Polycystic (Dysgenetic) Disease
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• Chronic Sclerosing Sialadenitis
• ( Kuttner Tumor )

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IGg4
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Myoepithelioma
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Myoepitheliomas

• Account for 1-2 of all salivary neoplasms
• Equal sex distribution
• Average age 40-50 yrs. (range 14-81)
• Usually present as a slowly enlarging, painless
  1-5 cm. mass.

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Myoepitheliomas

• Firm, white, tan, yellow or gray
• May or may not be encapsulated
• Composed of plasmacytoid, spindle, clear,
  epithelioid or oncocytic cells. Mix patterns are
  common

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Myoepitheliomas

• EM shows basal lamina, desmosomes, tonofibrils,
  and myofilaments
• 80-90 benign, 10-20 malignant

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Myoepitheliomas(N42)

• Parotid 21 50
• Palate 11 26
• Submandibular 5 12
• Lip 2 5
• Cheek 1 2
• Gingiva 1 2
• Retromolar 1 2
• Barnes L, et al. J Surg Oncol 2821, 1985

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Variants of Myoepithelial Cells

• Plasmacytoid
• Spindle
• Clear Cell
• Epithelioid
• Oncocytic

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Patterns of Myoepitheliomas

• Solid
• Mucinous
• Nodular
• Reticular
• Pseudoglandular

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Neoplastic Myoepithelium - IPEX

• Positive Positive/Negative Negative
• CK (AE1/AE3) SMA EMA
• Vimentin SMMHC CEA
• S100 Cam 5.2 CK7
• Calponin CK 14 B72.3
• p63 CK5/6 Desmin
• 34ße12 Maspin HHF-35
• CD10 GFAP
• Savera AT, Zarbo RJ Adv Anat Pathol 1169, 2004

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IPEX Profile of 18 Myoepithelial Carcinomas

• AE 1/3- 100 SMA- 50
• CK-14- 53 MSA- 31
• S-100- 100 Vimentin- 100
• GFAP- 31 Calponin- 75
• Savera, et al. Am J. Surg Pathol 24761, 2000

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Myoepithelial Carcinoma

• Malignant Myoepithelioma

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Myoepithelial Carcinoma

• Mean age 50-60 yrs.(14-86 yrs)
• MF ranges from 11 to 12
• Location (N70)
• Parotid 64
• Submandibular 13
• Minor 23
• AFIP, Savera and Nagao

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Myoepithelial Carcinoma

• Mean size 3.5- 5.0 cm. (2-20 cm.)
• 55-70 associated with pre-existing benign tumor

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Criteria of Malignancy

• Cellular pleomorphism
• Mitosesmore than 7/10 hpfs
• Perineural and angiolymphatic invasion
• Local invasion
• Necrosis
• Ki-67 index greater than 10
• Aneuploidy and p53 overexpression

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Myoepithelial Carcinoma

• 22-67 Local Recurrence
• 23-47 Mets (lungs, liver, bone, nodes)
• 29-47 DOD (2 mos 35 yrs mean 32 mos.
  in one study)