This study validates the current N classification system, supports the adverse effect of immunosuppression, and suggests that intense follow-up for 2 years postsurgery is warranted. Survival at this regional center is comparable to that achieved at metropolitan tertiary cancer centers.

Askin tumors are highly malignant small-round-cell tumors of the thoracopulmonary region, which occur rarely. Therefore, we report on our experiences with eight patients (5 male, 3 females), who were treated in our department between 11'94 and 10'97 (age: 9-40 years, mean age: 20.5 years). All Askin tumors were diagnosed by histological and immunohistochemical examinations as well as molecular genetic proof of characteristic translocations. In all patients, the tumor arose from the chest wall, infiltrating adjacent ribs and parts of the lung. At the time of first diagnosis, five patients did not reveal any metastases. One patient suffered from intrapulmonary metastases and two patients from an infiltration of the diaphragm and of adjacent vertebral bodies. Treatment consisted of a pre- and postoperative (radio-) chemotherapy according to the EVAIA protocol and a radical tumor resection in all patients. The postoperative course was uneventful in seven patients, one patient suffered from pneumonia after multiple wedge resections for intrapulmonary metastases. Four patients, in whom primary tumor resection was complete, are alive 14, 20, 35 and 84 months after first diagnosis - only one patient had to undergo a second operation for a local relapse 17 months after first diagnosis. The other 4 patients, who suffered from a very extensive primary tumor, expired 13, 17, 18 and 39 months after the diagnosis was made. Our data demonstrate that Askin tumors require an aggressive multimodality treatment consisting of pre- and postoperative chemotherapy, radical surgical resection and postoperative irradiation, which may be performed preoperatively in selected cases, too.

Perineural spread of tumour cells along cranial nerves is a severe complication of primary cutaneous squamous cell carcinomas of the head and neck region. While surgical excision of the tumour is the treatment of choice, removal of all the tumour is often complicated by the neural location and recurrence is frequent. Non-invasive immune treatments such as checkpoint inhibitor blockade may be useful in this set of tumours although little is understood about the immune response to perineural spread of squamous cell carcinomas. Immunohistochemistry studies suggest that perineural tumour contains a lymphocyte infiltrate but it is difficult to quantitate the different proportions of immune cell subsets and expression of checkpoint molecules such as PD-1, Tim-3 and CTLA-4. Using flow cytometry of excised perineural tumour tissue, we show that a T cell infiltrate is prominent in addition to less frequent B cell, NK cell and NKT cell infiltrates. CD8 T cells are more frequent than other T cells in the tumour tissue. Amongst CD8 T cells, the frequency of Tim-3, CTLA-4 and PD-1 expressing cells was significantly greater in the tumour relative to the blood, a pattern that was repeated for Tim-3, CTLA-4 and PD-1 amongst non-CD8 T cells. Using immunohistochemistry, PD-1 and PD-L1-expression could be detected in close proximity amongst perineural tumour tissue. The data suggest that perineural SCC contains a mixture of immune cells with a predominant T cell infiltrate containing CD8 T cells. Elevated frequencies of tumour-associated Tim-3+, CTLA-4+ and PD-1+ CD8 T cells suggests that a subset of patients may benefit from local antibody blockade of these checkpoint inhibitors.