Download I shall talk after you- my topic is Salivary glands, recent

EscoP Courses in Pathology
Belgrade 2011, Serbia
Head and neck Pathology, 7-9 April 2011
New entities and recent developments in salivary gland pathology
Alena Skálová, MD, PhD
Charles University in Prague
Medical Faculty in Pilsen
The review describes the new findings on salivary gland pathology. Newly recognized
entities include sclerosing polycystic adenosis (SPA) initially believed to be
reactive/inflammatory lesion similar to fibrocystic disease of breast (1). Recent molecular
study using the HUMARA (human androgen receptor assay) for clonality analysis
demonstrated that SPA is clonal, and thus most likely neoplastic process (2).
Mammary analogue secretory carcinoma (MASC) of salivary glands was recently
described as a new entity characterized histologically by resemblance to secretory breast
cancer (3). It was demonstrated that MASCs harbour a recurrent balanced chromosomal
translocation t(12;15)(p13;q25), which leads to a fusion gene between the ETV6 gene from
chromosome 12 and the NTRK3 gene from chromosome 15, exactly as in secretory breast
cancer (3).
Cribriform adenocarcinoma of the tongue (CAT) is an infiltrative tumor that
occurs almost exclusively in the base of the tongue characterized by synchronous metastases
in lateral neck lymph nodes, but no distant spread (4). In 1999, we published a series of this
distinctive type of adenocarcinoma occurring typically in the posterior tongue and
retromolar region (4). These tumors were designated cribriform adenocarcinoma of the
tongue (CAT) (4). The tumor was recognized by the latest issue of the WHO classification as a
possible variant of PLGA, but it was noted that it was not yet clear whether this represented
a genuine separate entity (5). Therefore, over the subsequent years, we have collected a
new series of 23 cases of these tumors, some of which arose in minor salivary glands other
than in the tongue (6). All the patients in our latest series were adults with a mean age at
diagnosis of 55.8 years (range 25-85). Fourteen of the 23 tumors were localized in the
tongue, three in the soft palate, two in the retromolar buccal mucosa, three in the lingual
tonsils, and one in the upper lip. Fifteen patients out of 23 had synchronous metastases in
the cervical lymph nodes at the time of diagnosis, bilateral in three cases; in 3 patients, the
nodal metastasis was the first evidence of disease, later investigation revealing primary
neoplasms in the base of tongue and tonsil, respectively. In addition, one patient developed
a cervical lymph node metastasis 8 years after excision of a primary tumor of the tongue.
Data on treatment and follow-up were available in 14 cases. The patients were treated by
radical excision with clear margins (12 cases) or by simple excision (2 cases). Neck dissection
was performed in 10 patients; nine received radiotherapy, but none was treated by
chemotherapy. Twelve patients are alive with no evidence of recurrent or metastatic disease
after treatment, one patient died two years after surgery without evidence of tumor, and
one patient is alive with recurrent tumor of the palate (6). In short, we believe the present
study shows that CATS is a distinct tumor entity that differs from PLGA by location (i.e. most
often arising on the tongue), cytology, histological architecture, and behavior, with frequent
metastases at the time of presentation of the primary tumor (6).
In addition, old salivary gland tumor entities with new findings were included, such as
salivary duct carcinoma (SDC) with newly recognized morphological variants (7,8), and a
proposal of molecular classification (9). SDC and invasive breast ductal carcinomas have
remarkably similar morphological features. Microarray studies have demonstrated that the
latter can be subclassified into biologically and clinically meaningful molecular subgroups:
luminal, molecular apocrine, HER2 and basal-like cancers. In our recent study of forty-three
pure salivary duct carcinomas (10), the immunohistochemical panel previously validated for
breast cancer was applied in order to determine whether SDC could likewise be classified
into analogous molecular groups. SDC cases were stained with antibodies for estrogen
receptor (ER), progesterone receptor (PR), androgen receptor (AR), HER2, epidermal growth
factor receptor (EGFR) and cytokeratin 5/6. HER2 status was assessed by
immunohistochemistry and silver in situ hybridisation. Cases were classified as HER2 positive
if they expressed HER2 protein and harboured the HER2 gene amplification, regardless of
the expression of other markers. Tumors lacking HER2 expression which expressed either ER,
PR or AR were considered of ‘luminal’/molecular apocrine phenotype, again regardless of
the expression of other markers. Cases negative for HER2, ER, PR or AR which expressed
either EGFR or Ck 5/6 were considered of ‘basal-like’ phenotype. Carcinomas which were
negative for all markers were considered of indeterminate phenotype. Analysis revealed
that 16.3% of the tumours were of HER2 phenotype, 67.4% were of ‘luminal’/molecular
apocrine phenotype, 7% were of basal-like phenotype and 9.3% were of indeterminate
phenotype. Interestingly, the in situ and invasive components displayed the same molecular
subtype in all but one case. Our results demonstrate that SDC can be classified into
molecular subgroups approximately equivalent to those in the breast. Understanding the
phenotypic complexity of SDCs may help expedite the development of novel therapeutic
targets for these usually very aggressive tumors (10).
Selected References:
1. Skálová A, Michal M, Simpson RHW, Stárek I, Přádná J, Pfaltz M. Sclerosing polycystic
adenosis of parotid gland with focal dysplasia and ductal carcinoma in situ. Report of
three cases with immunohistochemical and ultrastructural examination. Virchows
Arch 2002:440:29-35.
2. Skalova A, Gnepp DR, Simpson RH, et al. Clonal nature of sclerosing polycystic
adenosis of salivary glands demonstrated by using the polymorphism of the human
androgen receptor (HUMARA) as a marker. Am J Surg Pathol 2006: 30:939-944.
3. Skálová A, Vaneček T, Šíma R, Laco J, Weinreb I, Perez-Ordonez B, Stárek I, Geierová
M, Simpson RHW, Passador-Santos F, Ryska A, Leivo I, Kinkor Z, Michal M. Mammary
analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion
gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol
2010:34:599-608.
4. Michal M, Skalova A, Simpson RH, et al Cribriform adenocarcinoma of the tongue: a
hitherto unrecognized type of adenocarcinoma characteristically occurring in the
tongue. Histopathology 1999: 35:495-501.
5. Luna MA, Wenig BM. Polymorphous low-grade adenocarcinoma. In: Barnes EL,
Eveson JW, Reichart P, et al, eds. World Health Organization Classification of
Tumours. Pathology and Genetics of Head and Neck Tumours. Lyon, IARC Press, 2005,
pp. 223-224.
6. Skalova A, Sima R, Kaspirkova-Nemcova J, Simpson RHW, Elmberger G, Leivo I, Di
Palma S, Jirasek T, Gnepp RD, Weinreb I, Perez-Ordoñez B, Mukensnabl P, Rychly B,
Michal M. Cribriform Adenocarcinoma of the Tongue and Other Minor Salivary
Glands: Characterization of New Entity. Am J Surg Pathol 2011- accepted.
7. Simpson RH, Prasad AR, Lewis JE, Skalova A, David L. Mucin rich variant of salivary
duct carcinoma: a clinicopathologic and immunohistochemical study of four cases.
Am J Surg Pathol 2003:27:1070-1079.
8. Nagao T, Gaffey TA, Visscher DW, et al. Invasive micropapillary salivary duct
carcinoma: a distinct histologic variant with biologic significance. Am J Surg Pathol
2004: 28:319-326.
9. Di Palma S, Skalova A, Ungari M, et al. Pure salivary duct carcinoma can be classified
into luminal, HER2 and basal-like phenotypes. (Abstract). Mod Pathol 2008:21 (Suppl
1):234A.
10. Di Palma S, Simpson RHW, Skálová A, Ungari M, Sandison A, Whitaker S, Parry S,
Marchiò C, Reis-Filho JS. Pure salivary duct carcinomas can be classified into luminal/
molecular apocrine, HER2 and basal-like phenotypes. Submitted in Histopathology
2011.