Carcinomas indiferenciados de glándula salival
Nuevos conceptos en la clasificación y el diagnóstico
Llúcia Alòs
Hospital Clínic, Universidad de Barcelona
Carcinomas indiferenciados de glándula salival
• Uncommon malignant epithelial neoplasms that lack
histomorphological features of either glandular or
epidermoid differentiation and cannot be characterized
as any other type of salivary gland carcinoma.
• A broad definition of undifferentiated carcinoma includes
three types:
*high-grade neuroendocrine carcinomas (small and
large cell types)
*lymphoepithelial carcinoma
*large cell undifferentiated carcinoma
WHO, AFIP
Case 1. Clinical history
• A 54 year-old man complained of a painless, rapidly growing mass in right parotid region for 2 months.
• The CT-scan disclosed a tumoration in parotid gland 2 cm. in diameter.
• No other tumours in the head and neck region or lung were detected.
• A fine-needle aspiration cytology of the tumor was performed before the surgical excision of the right parotid gland.
Immunophenotype
Epithelial markers:
*Pan-cytokeratins
*Low molecular weight cytokeratins
CAM5.2
Neuroendocrine markers: *CD56(neural adhesion molecule) *synaptophysin
*neuron-specific enolase
*neurofilament
neurofilament
TTF-1 negative
Diagnosis
Small-cell carcinoma of salivary gland
(high-grade neuroendocrine carcinoma,small cell type)
Small-cell carcinoma of the salivary gland Clinicopathological data
• Most high-grade neuroendocrine carcinomas of salivary gland
• 80% in parotid gland; less frequently in submandibular gland;
rarely in minor salivary glands
• Most patients are over 60. Slight predilection for males.
Small-cell carcinoma of the salivary gland
Subclassification into *Merkel cell type: CK20-positive (75% of cases) or *pulmonary type:CK20-negative (25% of cases)
CK20 CK7
Treatment and follow-up of the patient
• Treatment: surgical resection, radiotherapy and
chemotherapy
• The patient is alive, without disease, after 40 months
of follow-up
79 y-o male
Tumour in parotid gland
Immunophenotype
Epithelial markers:
*Pan-cytokeratins
*Low molecular weight cytokeratins
Neuroendocrine markers: *CD56(neural adhesion molecule) *synaptophysin
*neuron-specific enolase
TTF-1 negative CK20
CK 20 negative
CAM5.2
Treatment and follow-up of the patient
• Treatment: surgical resection, radiotherapy and
chemotherapy
• The patient presented cervical lymph nodes
metastases, after 6 months of diagnosis
Small-cell carcinoma of the parotid gland
• Local recurrence and distant metastases develop in more than 50% of cases
Nagao T et al. Am J Surg Pathol 2004; 28:762- 770.
Prognostic
factors
Differential diagnoses
metastases of small-cell carcinoma from other organs
Ordoñez NG Am J Surg Pathol 2000; 24:1217-23.
La Pedrera, Barcelona
Case 2. clinical history
• A 52 year-old chinese man with antecedents of chronic sinusitis
which required surgical treatment, presented a tumoration in right
parotid region for 5 months.
• The CT-scan disclosed a tumoration in parotid gland 2 cm. in
diameter. No cervical adenopathies were detected.
• No other tumorations in the upper respiratory tract or lung were
detected.
34BE12
34BE12
CAM5.2
EBER
CD8 TIA-1
Diagnosis
Lymphoepithelial carcinoma of the salivary gland
Lymphoepithelial carcinoma of the salivary glands
Etiologic factors
Epstein-Barr virus (EBV) infection
Benign lymphoepithelial lesion
Kutok JL.Annu Rev Pathol 2006
Ng and Khoury, Adv Anat Pathol 2009
Epstein-Barr virus: latency patterns
Lymphoepithelial carcinoma of the salivary glands
Epidemiology
Endemic areas:
* Genetic predisposition: HLA phenotype
Eskimos/Inuits (Greenland, Canada, Alaska)
Asians (Southeastern China, Japan)
* Oncogenic variants of EBV
* Environmental factors (salted fish)
Lymphoepithelial carcinoma of the salivary gland Clinicopathological data
• The most frequent malignant salivary gland tumour in endemic
areas ; 1% of malignant salivary gland carcinomas in non
endemic areas.
• 80% in parotid gland; 20% in submandibular gland
• Most patients are in the 5th decade of life. Slight predilection for
females.
60 y-o caucasian female
Tumour in parotid gland
EBER
Lymphoepithelial carcinoma of the salivary gland
Treatment and follow-up
• About 40% of patients present cervical lymph node
metastases and 20%, distant metastases
• Treatment : surgical resection, radiotherapy and/or
chemotherapy, depending on stage
• Overall survival is 60-80% at 10 years
Parc Güell, Barcelona
Case 3. clinical history
• A 77 year-old man presented with a tumoration in right parotid
region very rapid growth for 1 month and facial nerve palsy.
• The CT-scan disclosed a tumoration in parotid gland 3.6 cm. in
diameter and multiple cervical adenopathies.
• No other tumours in the head and neck region or lung were
detected.
Immunophenotype
*LMW cytokeratins positive
*HMW cytokeratins positive
*neuroendocrine markers negative
34BE12
CAM5.2
Diagnosis
Large-cell undifferentiated carcinoma
of the salivary gland
Large-cell undifferentiated carcinoma of the salivary gland Clinicopathological data
• 1 to 20% of malignant salivary gland carcinomas, depending on
published series
• 80% in parotid gland; less frequently in submandibular gland;
rarely in minor salivary glands
• Peak incidence in 7th decade. Slight predilection for males.
• The tumours grow rapidly. Lymph node metastases and facial
nerve palsy are very frequent
Large-cell undifferentiated carcinoma of the salivary gland Histological characteristics
• Sheets of large cells (30 m), polygonal with eosinophilic cytoplasm. Pleomorphic nuclei, prominent nucleoli.
• Frequent necrosis, vascular and perineural invasion.
• Lack of acinar, ductal or myoepithelial differentiation.
• Frequent lymphoid inflammatory infiltrate.
CD8
Lymphoepiehelial carcinoma
vs.
Large cell undifferentiated carcinoma
Wang CP et al. Cancer 2004; 101:2020-7
NUT-rearragement midline carcinomas
• Morphology of large-cell undifferentiated or poorly differentiated
carcinomas
• Translocation t(15;19) (q13; p13.1): BRDT-NUT fusion oncogene
More than 50% in the head and neck region
(upper respiratory tract, salivary glands)
Prevalence in young patients. No gender predilection
Highly lethal clinical course; unresponsive to chemoradiotherapy
15 y-o male
Sumandibular gland
Ziai J, et al. Head and Neck Pathol 2010; 4:163-168
Haack H et al. Am J Surg Pathol 2009; 33:984-991
0
10
20
30
40
50
60
70
Small CC LEC LC Undiff NUT
male
female
age
tumour type
Undifferentiated carcinomas of the salivary glands
Large-cell undifferentiated carcinoma of the salivary glands Differential Diagnoses
• Metastases of undifferentiated carcinomas from the upper respiratory tract and lung
• Adenoid-cystic carcinoma solid type
• (focal glandular differentiation and myoepithelial component)
• Malignant melanoma
• (S100 protein, melanA, HMB45)
• Non-Hodgkin lymphoma (lymphoid markers)
Metastases of undifferentiated carcinomas from
the upper respiratory tract
Oropharynx
large cell undifferentiated/ lymphoepithelial-like carcinomas
are frequently related to HPV- infection
Nasopharynx
large cell undifferentiated/lymphoepithelial carcinomas are
related to EBV infection
Hypopharynx, Larynx
large cell undifferentiated/ lymphoepithelial-like carcinomas
are usually not related to HPV or EBV infections
Nasopharyngeal undifferentiated carcinoma
50 y-o man
EBER
Oroparyngeal lymhoepithelioma-like carcinoma
60 y-o woman
p16
HPV16
Thank you
Contributors:
Alessandro Franchi, University of Florence
Montse Gomà, Hospital de Bellvitge, Barcelona
Leonardo Rodriguez, Hospital Clínic of Barcelona