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Aims: NUT midline carcinoma (NMC) is a rare undifferentiated and aggressive carcinoma that locates characteristically to the midline of the head and neck, and mediastinum. NMC is characterized by chromosomal rearrangements of the gene NUT, at 15q14. The BRD4 gene on 19q13 is the most common translocation partner forming a fusion oncogene, BRD4-NUT. By the end of 2014, the International NUT Midline Carcinoma Registry had 48 patients treated for NMC. Laryngeal NMC are exceedingly rare, and we report a case series of seven cases., Methods and Results: We searched for cases in files of different hospitals as well as a thorough search of the English language literature. The diagnosis of NMC is made by demonstration of NUT rearrangement either by immunohistochemistry, fluorescence in-situ hybridization (FISH) or reverse transcription-polymerase chain reaction (RT-PCR). We found three previously published cases, and in this series add four cases of our own., Conclusions: NMC consists of monomorphic, often discohesive, cells with an epithelioid appearance and distinct nucleoli. The tumours typically show abrupt squamous differentiation. The mean age of the patients was 34 years, hence significantly lower than that for conventional laryngeal carcinoma. All tumours were located in the supraglottis and five patients died of the disease after 3, 7, 8, 9 and 11 months. Laryngeal NMC may be underdiagnosed, and an increased awareness among pathologists is warranted. NMC has characteristic morphological features, and positive immunostaining with the NUT antibody is diagnostic. Its aggressive behaviour demands a very intense treatment strategy and the need for its recognition is emphasized further by new promising treatment strategies., (© 2016 John Wiley & Sons Ltd.)

Aims: To validate histological criteria for the grading of epithelial hyperplastic laryngeal lesions (EHHL) (dysplastic laryngeal lesions), we used a system that had been devised and tested in Ljubljana, Slovenia over many years and was felt to be more appropriate to laryngeal pathology than is the commonly-used model of intraepithelial neoplasia in the cervix., Methods and Results: Vocal cord biopsies of 45 patients with a broad spectrum of EHLL were reviewed. Detailed histological criteria were formulated for each of the four grades of EHLL in the Ljubljana classification, comprising simple hyperplasia (benign spinous layer augmentation), abnormal hyperplasia (benign basal and parabasal layer augmentation), atypical hyperplasia (risky for malignancy) and carcinoma in situ (actually malignant, but without invasion)., Conclusions: Using these criteria a high degree of concordance of histological diagnoses of grading levels for the Ljubljana classification was achieved between the pathologists of the Working Group. The system was found to be more precise for routine diagnostic work than the others in vogue. The different grades of the Ljubljana classification correspond to significantly different levels yielded in each grade by the semiobjective methods of quantitative morphometry and immunohistochemistry.

We describe the pathological features of a case of laryngeal epithelioid leiomyoma (leiomyoblastoma) which, to our knowledge, is the second case to be reported in the world literature. A review of the literature confirmed that leiomyoma as such is a very rare neoplasm in the larynx, and only 33 cases have been previously reported. The neoplasm was located in the left vocal cord and consisted of mainly epithelioid, round or spindle-shaped cells, often with clear cytoplasm, which were arranged predominantly in solid nests and sheets. The tumour cells showed positive immunoreactivity for smooth muscle actin and desmin. The tumour showed low mitotic activity and immunostaining with MIB 1 (Ki-67) accordingly revealed the occasional cell only to be positive, confirming a low proliferative activity in agreement with a benign neoplasm. Epithelioid leiomyomas located in other sites have been shown to act occasionally in a malignant fashion, and the necessity for careful long-term follow-up of the patient is therefore emphasized.

The expression of EGFR was determined immunohistochemically in two groups of patients with glottic carcinoma, one that recurred after a full course of radiotherapy and one that did not. Using a 4-graded scale (-,+,++, ) 80% (12/15) of the recurrent carcinomas had a staining intensity and proportion of stained cells of ++ or more. The same figure for non-recurrent carcinomas was 39% (7/18). The difference is statistically significant (chi-squared with Yates' correction, P less than 0.05). The results indicate that an increased expression of EGFR may influence the rate of recurrence of glottic squamous cell carcinoma after radiotherapy.

Comparison of reported series of laryngeal lesions is complicated by the inconsistency in the terminology. The classification of these lesions should logically be based on the degrees of dysplasia, as this has a bearing on the prognosis. The material for this study consisted of 193 patients with hyperplasia and/or keratosis, with or without mild dysplasia (Group I), moderate dysplasia (Group II), and severe dysplasia and carcinoma in situ (Group III). They were treated over a 14-year period (1966-1979) at Linköping University Hospital. Of the 98 patients in Group I available for follow-up, 23 had repeat excisions. Moderate dysplasia developed in 3 patients, severe dysplasia in 2, and invasive carcinoma in another 2 within 3 and 3.5 years; they both underwent laryngectomy. Among the 24 patients in Group II available for follow-up, severe dysplasia developed in 3 and invasive carcinoma in 3 up to 13 years after the initial diagnosis, all but one (with severe dysplasia) received a full course of radiotherapy, on one case total laryngectomy was subsequently performed for recurrent carcinoma. Of the 39 patients with severe dysplasia and carcinoma in situ 16 were given primary radiotherapy; 4 of these developed invasive carcinoma; 3 of them underwent total laryngectomy and one partial laryngectomy. Excision or stripping of the vocal cords was the primary treatment in 23 cases; 5 of these developed invasive carcinoma; 2 of them underwent total laryngectomy. Diffuse lesions and well differentiated forms of severe dysplasia caused most problems and had the highest incidence of invasive carcinoma irrespective of the form of treatment. Patients with hyperplasia, keratosis, dysplasia and carcinoma in situ should be carefully followed up, as invasive carcinoma may develop many years after the initial diagnosis.

Twelve human laryngeal carcinomas and 14 normal vocal cord epithelia were studied in vitro by the method of tissue culture incorporating video time-lapse microscopy. Different events were photographed by taking 'stills' from the television monitor during play-back. Outgrowths from both tumour and normal explants formed only as monolayers. Mitoses were mainly found to be localized approximately mid-way between explant and the edge of the outgrowth. Some cells were seen to become suddenly active producing oscillating blebs and sometimes they detached themselves from the monolayer culture and changed appearance. This was more prevalent in the tumour cultures. In both tumour and normal cell cultures lymphocytes were observed and their normal chemokinetic movement was changed into a rapid chemotactic attraction by the presence of a mitotic epithelial cell. These lymphocytes appear to represent T-suppressor cells. The present study has shown that primary tissue culture can be a valuable tool in the study of laryngeal carcinoma. The interaction between mitotic tumour cells and lymphocytes may represent a transformation of T-lymphocytes into LAK cells.