Immunohistochemical and HPV-related features of laryngeal adenosquamous carcinoma




Abstract


Background


Adenosquamous carcinoma (ASC) of the head and neck is a rare malignancy characterized by loco-regional and distant aggressiveness. At histology, ASC reveals two distinct, juxtaposed components, squamous cell carcinoma (SCC), and true adenocarcinoma.


Methods


The immunohistochemical expression of AE3, CK19 and CAM5.2, and HPV infection was tested in a case of laryngeal ASC.


Results


The patient had no regional lymph node metastases, but developed a recurrence in neck soft tissues shortly after primary radical surgery. The laryngeal surgical specimen had the typical morphological features of ASC. The tumor’s squamous and glandular components were both strongly and diffusely immunoreactive for AE3 and CK19, whereas CAM5.2 selectively stained only the gland-like part. We found no high- or low-risk HPV DNA (28 genotypes) in the specimens. The patient underwent salvage extended radical neck dissection and received postoperative radio-chemotherapy. At 4-month follow-up control, neck recurrence was found. Palliative chemotherapy was instituted.


Conclusions


An accurate histological and immunohistochemical diagnosis is mandatory to differentiate ASC from conventional SCC. Radical surgical excision is recommended for laryngeal ASC. Adjuvant postoperative therapy is administered in most cases, but there are no widely accepted indications for these treatments.



Introduction


Adenosquamous carcinoma (ASC) of the head and neck is quite a rare malignancy, histopathologically featuring both squamous cell carcinoma (SCC) and true adenocarcinoma, as defined by the World Health Organization (WHO) in 2005 , and somewhat similarly by the Armed Forces Institute of Pathology (AFIP) group in 2008 . On histological examination, the two components of ASC are separate but closely juxtaposed. SCC usually predominates, ranging from well- to poorly-differentiated. The adenocarcinomatous component typically features ductular structures with trabeculae and solid tumor nests at the infiltrating tumor’s edge. Mucin production is often apparent, but (unlike the presence of true gland formation) it is not a requirement for diagnosis. Gland formation classically consists of “punched out” spaces with smooth (rather than ragged) boundaries . The glandular component typically expresses carcinoembryonic antigen (CEA) and low-molecular-weight cytokeratins (CKs) . The idea of ASC of the head and neck as a separate entity remained controversial for several years because it was considered a high-grade mucoepidermoid carcinoma (MEC) , but its decidedly worse prognosis (than even high-grade MEC) and morphological and clinical differences justify the distinction between these entities .


Little is known about the etiopathogenesis of ASC of the head and neck, mainly because of its rarity. There is little room for doubt about its loco-regional and distant aggressiveness, however . Laryngeal ASC is usually already advanced at the time of its diagnosis . Here we report a case of laryngeal ASC that recurred in the neck soft tissues 4 months after pathologically radical primary surgery.





Case report


A 55-year-old diabetic man, formerly a heavy-smoker, was referred to the Otolaryngology Section of Padova University, complaining of a six-month history of hoarseness. Upper aero-digestive tract endoscopy revealed an ulcerated lesion of the anterior third of both true vocal folds and evidence of left larynx fixation. Clinical examination of the neck was negative.


The patient underwent microlaryngoscopy under general anesthesia: the lesion involved the anterior third of the true vocal folds, the anterior commissure and the left laryngeal ventricle. Histological examination of laryngeal biopsies identified a moderately-differentiated SCC. Head and neck contrast-enhanced computerized tomography (CT) showed a thickening of the true vocal folds with no involvement of the cartilages or pre-epiglottic and paraglottic spaces. Multiple enlarged neck lymph nodes with an uneven contrast enhancement were disclosed on the left side. Chest x-ray, and liver ultrasonography were normal.


A supracricoid laryngectomy with crico-hyoido-epiglottopexy and bilateral selective neck dissection (left ND [II-IV], right ND [II-IV]) was performed together with a temporary tracheostomy. Histology on the surgical specimen was consistent with laryngeal ASC ( Fig. 1 A ) with free surgical margins and no perineural, lymphatic or vascular invasion. No metastases were found in the 55 neck lymph nodes assessed. The tumor’s squamous and glandular components were both strongly and diffusely immunoreactive for AE3 (mouse monoclonal, 1:100; Progen, Heidelberg, Germany; Fig. 1 B) and CK19 (mouse monoclonal, 1:100; Dako, Glostrup, Denmark; Fig. 1 C), while CAM5.2 selectively stained only the gland-like part (mouse monoclonal, 1:50; Becton Dickinson, San Jose, USA; Fig. 1 D). HPV detection and typing were performed on genomic DNA extracted from formalin-fixed, paraffin-embedded tumor samples using the INNO-LiPA HPV Genotyping Extra assay (Innogenetics, Gent, Belgium), as described elsewhere . No high-risk HPV DNA (genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82), probable high-risk HPV DNA (genotypes 26, 53, 66), low-risk HPV DNA (genotypes 6, 11, 40, 43, 44, 54, 70), or other HPV DNA (genotypes 69, 71, 74) were found in the present case. The patient was assessed by a multidisciplinary team including a radiotherapist and an oncologist, who found no indication for postoperative adjuvant treatment. Daily swallowing rehabilitation began after the tenth postoperative day. The patient was discharged after a hospital stay of 1 month, when he was capable of normal oral feeding.




Fig. 1


Micrograph showing squamous (upper right) and glandular (lower left) components of the tumor (A). Both areas are strongly and diffusely immunoreactive for AE3 (B) and CK19 (C), while CAM5.2 focally stained only the gland-like part (D). (Original magnification 5 ×).


A right neck swelling was found at 4-month postoperative follow-up, and a head and neck contrast-enhanced CT scan disclosed a hypodense, solid mass 2.5 cm in size with peripheral contrast enhancement located at the bifurcation of common carotid artery, and multiple enlarged lymph nodes. Fine needle aspiration cytology of the mass revealed atypical cells with keratinized orangephilic cytoplasm and intercellular bridges. Right extended radical neck dissection was performed, extending it to the right external carotid artery. Histology was conclusive for ASC involving the soft tissues with perineural, lymphatic, and vascular invasion; the pathologist that assessed the lymph nodes of the extended radical neck dissection found no metastases. After discharge, the patient was administered postoperative radiotherapy to the neck (64 Gy in 32 fractions) plus concurrent weekly platinum (35 mg/m 2 ). At 4-month follow-up control after completing adjuvant treatment, further right neck recurrence was diagnosed. Palliative chemotherapy was instituted. Nowadays the patient is alive with evidence of disease.





Case report


A 55-year-old diabetic man, formerly a heavy-smoker, was referred to the Otolaryngology Section of Padova University, complaining of a six-month history of hoarseness. Upper aero-digestive tract endoscopy revealed an ulcerated lesion of the anterior third of both true vocal folds and evidence of left larynx fixation. Clinical examination of the neck was negative.


The patient underwent microlaryngoscopy under general anesthesia: the lesion involved the anterior third of the true vocal folds, the anterior commissure and the left laryngeal ventricle. Histological examination of laryngeal biopsies identified a moderately-differentiated SCC. Head and neck contrast-enhanced computerized tomography (CT) showed a thickening of the true vocal folds with no involvement of the cartilages or pre-epiglottic and paraglottic spaces. Multiple enlarged neck lymph nodes with an uneven contrast enhancement were disclosed on the left side. Chest x-ray, and liver ultrasonography were normal.


A supracricoid laryngectomy with crico-hyoido-epiglottopexy and bilateral selective neck dissection (left ND [II-IV], right ND [II-IV]) was performed together with a temporary tracheostomy. Histology on the surgical specimen was consistent with laryngeal ASC ( Fig. 1 A ) with free surgical margins and no perineural, lymphatic or vascular invasion. No metastases were found in the 55 neck lymph nodes assessed. The tumor’s squamous and glandular components were both strongly and diffusely immunoreactive for AE3 (mouse monoclonal, 1:100; Progen, Heidelberg, Germany; Fig. 1 B) and CK19 (mouse monoclonal, 1:100; Dako, Glostrup, Denmark; Fig. 1 C), while CAM5.2 selectively stained only the gland-like part (mouse monoclonal, 1:50; Becton Dickinson, San Jose, USA; Fig. 1 D). HPV detection and typing were performed on genomic DNA extracted from formalin-fixed, paraffin-embedded tumor samples using the INNO-LiPA HPV Genotyping Extra assay (Innogenetics, Gent, Belgium), as described elsewhere . No high-risk HPV DNA (genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82), probable high-risk HPV DNA (genotypes 26, 53, 66), low-risk HPV DNA (genotypes 6, 11, 40, 43, 44, 54, 70), or other HPV DNA (genotypes 69, 71, 74) were found in the present case. The patient was assessed by a multidisciplinary team including a radiotherapist and an oncologist, who found no indication for postoperative adjuvant treatment. Daily swallowing rehabilitation began after the tenth postoperative day. The patient was discharged after a hospital stay of 1 month, when he was capable of normal oral feeding.


Aug 23, 2017 | Posted by in OTOLARYNGOLOGY | Comments Off on Immunohistochemical and HPV-related features of laryngeal adenosquamous carcinoma

Full access? Get Clinical Tree

Get Clinical Tree app for offline access