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