Neoadjuvant presurgical PD-1 inhibition in oral cavity squamous cell carcinoma.

Oral cavity squamous cell carcinoma (OCSCC) is a prevalent surgically treated subset of head and neck cancer with frequent recurrence and poor survival. Immunotherapy has demonstrated efficacy in recurrent/metastatic head and neck cancer. However, whether antitumor responses could be fostered by neoadjuvant presurgical immunotherapy remains unclear. Using a Simon's two-stage design, we present results of a single-arm phase-II trial where 12 patients with stage II-IVA OCSCC received 3 to 4 biweekly doses of 3 mg/kg nivolumab followed by definitive surgical resection with curative intent. Presurgical nivolumab therapy in this cohort shows an overall response rate of 33% (n = 4 patients; 95% CI: 12%-53%). With a median follow up of 2.23 years, 10 out of 12 treated patients remain alive. Neoadjuvant nivolumab is safe, well-tolerated, and is not associated with delays in definitive surgical treatment in this study. This work demonstrates feasibility and safety for incorporation of nivolumab in the neoadjuvant setting for OCSCC (ClinicalTrials.gov: NCT03021993).

Microscopic Extranodal Extension in HPV-Negative Head and Neck Cancer and the Role of Adjuvant Chemoradiation.

OBJECTIVE: Pathologic extranodal extension (ENE) is an important adverse feature for human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), but the prognostic significance of microscopic ENE (ENEmi) and role of adjuvant concurrent chemoradiation (CRT) for ENEmi remain unclear. This study evaluates (1) the prognostic significance of ENEmi in HPV-negative HNSCC and (2) whether adjuvant CRT is associated with improved overall survival (OS) for these patients. STUDY DESIGN: Retrospective cohort study. SETTING: Commission on Cancer (CoC)-accredited facilities. METHODS: This retrospective cohort study included patients in the National Cancer Database from 2009 to 2015 with pathologic node-positive (pN+) HPV-negative HNSCC with either pathologic ENEmi or no ENE who had undergone margin-negative surgery. The association of ENEmi with OS was evaluated using Cox proportional hazard analyses. Analyses were repeated in patients with ENEmi receiving adjuvant therapy to evaluate the association of adjuvant CRT with OS. RESULTS: We included 5483 patients with pN+ HPV-negative HNSCC, of whom 24% had ENEmi. On multivariable analysis, ENEmi was associated with decreased OS relative to no ENE (adjusted hazard ratio [aHR], 1.43; 95% CI, 1.28-1.59). Among patients with ENEmi who received ≥60 Gy of adjuvant radiation therapy (RT) (n = 617), adjuvant CRT was not associated with improved OS relative to RT (aHR, 0.91; 95% CI, 0.66-1.27). CONCLUSION: For patients with HPV-negative HNSCC, pN+ with ENEmi is associated with worse OS than pN+ without ENE. However, for patients with ENEmi, concurrent CRT is not associated with improved OS relative to RT. The optimal adjuvant paradigm for ENEmi requires additional investigation.

Data Set for the Reporting of Malignant Odontogenic Tumors: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

A data set has been developed for the reporting of excisional biopsies and resection specimens for malignant odontogenic tumors by members of an expert panel working on behalf of the International Collaboration on Cancer Reporting, an international organization established to unify and standardize reporting of cancers. Odontogenic tumors are rare, which limits evidence-based support for designing a scientifically sound data set for reporting them. Thus, the selection of reportable elements within the data set and considering them as either core or noncore is principally based on evidence from malignancies affecting other organ systems, limited case series, expert opinions, and/or anecdotal reports. Nevertheless, this data set serves as the initial step toward standardized reporting on malignant odontogenic tumors that should evolve over time as more evidence becomes available and functions as a prompt for further research to provide such evidence.

Data Set for the Reporting of Oral Cavity Carcinomas: Explanations and Recommendations of the Guidelines From the International Collaboration of Cancer Reporting.

The International Collaboration on Cancer Reporting is a nonprofit organization whose goal is to develop evidence-based, internationally agreed-upon standardized data sets for each cancer site for use throughout the world. Providing global standardization of pathology tumor classification, staging, and other reporting elements will lead to the objective of improved patient management and enhanced epidemiologic research. Carcinomas of the oral cavity continue to represent a significant oncologic management burden, especially as changes in alcohol and tobacco use on a global scale contribute to tumor development. Separation of oral cavity carcinomas from oropharyngeal tumors is also important, as management and outcome are quite different when human papillomavirus association is taken into consideration. Topics such as tumor thickness versus depth of invasion, pattern of invasive front, extent and size of perineural invasion, and margin assessment all contribute to accurate classification and staging of tumors. This review focuses on the data set developed for Carcinomas of the Oral Cavity Histopathology Reporting Guide, with discussion of the key elements developed for inclusion.

Peritoneal Deciduoid Mesothelioma: An Unusual Presentation Complicating an Already Challenging Diagnosis.

This report highlights a diagnostically challenging case of diffuse deciduoid mesothelioma occurring in the peritoneum of a 25-year-old woman, 8 months postpartum. Optimally debulked tumor consisted of sheets of polygonal cells arranged in solid, trabecular, and pseudopapillary configurations, with vesicular, occasionally grooved nuclei and small nucleoli. A barrage of immunohistochemical stains revealed an unusual staining pattern characterized by diffusely positive keratin, WT-1, and mesothelin staining, but lack of calretinin positivity. Electron microscopy demonstrated only rare thin, long, branching cellular projections. Cytogenetics revealed balanced translocations of 12p and 1q and 16p. Based on compiled ancillary studies, a diagnosis of deciduoid mesolthelioma was made and supported by consultations from experts at 3 outside facilities. Twenty-seven months after diagnosis, the patient is alive and undergoing treatment with progression of disease. This case is presented in detail, and a discussion of the diagnostic criteria and current application of those criteria is provided.

Familiar and unfamiliar pseudoneoplastic lesions of the head and neck.

Pseudoneoplastic lesions in the head and neck are numerous. Familiarity with the sites of predilection and demographics of these lesions is particularly useful if the differential diagnosis for a minimal biopsy sample includes benign and malignant entities. This article is a brief overview of some common and unusual pseudo neoplasms specific to this region.

Malignant odontogenic tumors: an update on selected tumors.

This is an update on selected odontogenic malignancies. The article deals with aspects of recognized odontogenic carcinomas, odontogenic sarcoma and a yet unrecognized entity, sclerosing odontogenic carcinoma. Odontogenic malignancies are exceedingly rare, complicating a thorough understanding of the biologic behavior, reproducible standardized diagnostic criteria, appropriate classification and clinical management. Without the knowledge of the tumor's biologic behavior, adequate clinical management is difficult and patient outcomes uncertain. The histopathologic features are emphasized as well as the more recent biomarker findings. These recent advances may facilitate further understanding of this group of malignancies and provide useful stratification to guide patient management.

Sclerosing rhabdomyosarcoma: report of a case arising in the head and neck of an adult and review of the literature.

Sclerosing rhabdomyosarcoma is a unique rhabdomyosarcoma variant, characterized by a prominent hyalinizing matrix. A notable pitfall is the potential for the unusual matrix and often pseudovascular growth pattern of this lesion to lead to confusion with other sarcoma types, including osteosarcoma, chondrosarcoma, and angiosarcoma. Here we report a case of sclerosing rhabdomyosarcoma arising in a 40-year old male. The tumor was centered in the pterygomaxillary fossa with extensive infiltration into adjacent structures. Fine needle aspiration yielded a preliminary diagnosis of high-grade pleomorphic undifferentiated sarcoma, for which he received neoadjuvant chemotherapy and surgical resection. Microscopic examination showed a malignant spindled to round cell neoplasm with prominent osteoid-like, hyaline stroma. Focal rhabdomyoblastic differentiation and diffuse immunoreactivity for desmin and myogenin aided in diagnosis. Nineteen months status post primary resection, the patient expired with multiple lung and bony metastases. Among 39 cases reported thus far (including the present case), there is a broad age range (0.3-79 years), with an average age at presentation of 27 years. The most commonly involved sites are the extremities (n = 19) and head and neck (n = 15). Most cases have been treated by resection, often combined with radiation and/or chemotherapy. Out of 31 cases with follow-up information provided, 6 patients developed local recurrence, 7 patients developed regional or distant metastasis, and 5 patients died of disease. Herein we discuss the ongoing controversy regarding how sclerosing rhabdomyosarcoma might best fit into existing rhabdomyosarcoma classification schemes, based upon current clinicopathologic and molecular genetic evidence.

Intravascular fasciitis: report of an intraoral case and review of the literature.

Intravascular fasciitis (IF) is an unusual variant of nodular fasciitis. It is characterized by intraluminal, intramural, and extramural involvement of small to large arteries or veins. Only three cases involving the oral cavity have been reported previously in the literature. Here we present an additional case of oral IF arising in the submucosa of the upper lip of a 20-year old female. Microscopic examination showed a well-circumscribed, nodular proliferation of spindle cells arranged in intersecting fascicles. Occasional multinucleated giants cells also were noted. The tumor was present within the lumen of an intermediate-sized artery and extended into adjacent smaller vessels, thereby creating a multinodular appearance. Extramural extension into the surrounding connective tissue also was observed. Among the 31 cases of IF reported thus far (including the present case), the majority (n = 23) arose in individuals in the 1st through 3rd decades, with a 1.4:1 male:female ratio. The most common sites of involvement were the head and neck (n = 11) and upper extremity (n = 11), followed by the lower extremity (n = 6) and trunk (n = 3). Conservative excision is standard treatment, although local recurrence has been reported in three cases. It is important for the pathologist to be aware of this lesion in order to avoid misdiagnosis as a sarcoma with angioinvasion.

Oral mucoceles: a clinicopathologic review of 1,824 cases, including unusual variants.

PURPOSE: To review the clinicopathologic features of oral mucoceles, with special consideration given to unusual variants and exclusion of salivary duct cysts. MATERIALS AND METHODS: This was a retrospective consecutive case review of all oral mucoceles diagnosed by the Medical University of South Carolina, Oral Pathology Biopsy Laboratory, from 1997 to 2006. The following data were recorded: patient demographics, clinical features (anatomic location, color, size, and consistency), clinical impression, history of trauma, history of periodic rupture, and occurrence of unusual mucocele variants. RESULTS: During the study period, 1,824 oral mucoceles were diagnosed. Of these cases, 1,715 represented histopathologically confirmed cases that were not recurrences. There was no significant gender predilection, and the average age was 24.9 years. The most common locations were the lower labial mucosa (81.9%), floor of mouth (5.8%), ventral tongue (5.0%), and buccal mucosa (4.8%); infrequent sites included the palate (1.3%) and retromolar area (0.5%). The lesions most often were described as blue/purple/gray or normal in color. The mean maximum diameter was 0.8 cm (range, 0.1 to 4.0 cm). In 456 cases, a history of trauma was reported, and in 366 cases a history of periodic rupture was reported. Unusual variants included superficial mucoceles (n = 3), mucoceles with myxoglobulosis (n = 6), and mucoceles with papillary synovial metaplasialike change (n = 2). CONCLUSIONS: Our results confirm the findings of previous investigators regarding the major clinicopathologic features of oral mucoceles. Special variants of oral mucoceles occur infrequently, although it is important to recognize these variants to avoid misdiagnosis.

Common Lesions of the Larynx and Hypopharynx.

Benign and malignant lesions of the larynx and hypopharynx present an interesting and diverse spectrum of diagnostic entities, which may be infrequently encountered in routine surgical pathology practice. This article places emphasis on illustrating the classical pathologic characteristics, differential diagnosis, clinical significance, and presentation of common lesions unique to these sites. The initial diagnosis of these lesions is via small endoscopic biopsy. Many of the entities have overlapping histologic features which necessitate optimizing the information available in a small sample. The focus of this article is to provide useful criteria to enable separating the more common types of lesions encountered in these sites.

Co-occurrence of Langerhans cell histiocytosis and Rosai-Dorfman disease: possible relationship of two histiocytic disorders in rare cases.

Rosai-Dorfman disease and Langerhans cell histiocytosis are both disorders of accessory immune cells. Two cases have been previously reported of concurrent Langerhans cell histiocytosis and Rosai-Dorfman disease. In this report, we characterize the findings and selected molecular studies in nine additional cases. Histology was reviewed. Immunohistochemical stains were performed on all cases in which slides or blocks were available. A combination of CD1a, S-100, CD3, CD20, langerin, CD68, CD163, CD21, CD35 and CD123 immunohistochemical stains were performed. High-resolution array comparative genomic hybridization was performed on six samples from five cases. In these cases, seven were female and two male, with an average age of 25 years (15 months-59 years). A majority of the cases were identified in lymph node. Areas of Langerhans cell histiocytosis had a typical appearance with the existence of bland 'coffee-bean' nuclei, clear cytoplasm and associated eosinophils. The immunophenotype was typical, including expression of CD1a, S100, CD68 and langerin. In areas of Rosai-Dorfman disease, there was emperipolesis seen in all cases. Cells were intermediate-large in size with large round nuclei and ample clear or pale cytoplasm. The lesional cells were positive for S100, CD68, CD163, without expression of langerin or CD1a. Array comparative genomic hybridization showed gains and/or losses in four of the six samples. One case showed no gains or losses and one additional case showed gains and losses in the Langerhans cell histiocytosis, while no abnormalities were discovered in the Rosai-Dorfman disease component. These findings are comparable to those seen in previous studies of Langerhans cell histiocytosis. We report the clinical and pathologic findings of the combination of Langerhans cell histiocytosis and Rosai-Dorfman disease. Furthermore, we suggest on the basis of evidence from our cases that, when simultaneous, the two entities may be pathophysiologically related.

Neural outcomes after plasma knife dissection: a pathologic study and clinical correlation.

BACKGROUND: The initial aim was to determine the rate of pathologic tissue damage when dissecting the rat sciatic nerve with either bipolar forceps or low-temperature tripolar plasma knife. The second aim was to determine the safety and effectiveness of the plasma knife during parotid surgery. METHODS: A prospective, randomized, single-blind study was performed on 40 rat sciatic nerves dissected by either bipolar electrocautery with a cold knife or a plasma knife. Dissected nerves were excised and submitted blindly to pathology for analysis of nerve injury. The degree of nerve trauma was graded by the Carlander nerve injury classification. Separately, a review was performed on the facial nerve outcomes of 30 patients who underwent plasma knife parotidectomy. RESULTS: No thermal or neural injury was noted in the 40 rat sciatic nerves dissected by either bipolar electrocautery or plasma knife (p = 1.0). Two plasma knife-dissected nerves (8%) demonstrated significant numbers of mast cells in the perineural soft tissue. In 30 patients undergoing plasma knife-parotidectomy, 10 (33%) had mild weakness of 1 or 2 preserved facial nerve branch postoperatively (House-Brackmann 2) that resolved within 1 month, whereas 2 (7%) had visible weakness in 1 branch (HB 3) that normalized after 3 months of follow-up. CONCLUSION: Plasma knife nerve dissection seems to be a safe and effective alternative to conventional methods. This technique may confer some advantages over conventional methods with the ability to simultaneously cut and coagulate tissue with minimal thermal spread and electrical stimulation of adjacent neural structures.

Papillary synovial metaplasia-like change in oral mucoceles: a rare and previously undescribed histopathologic variant of a common oral lesion.

The development of synovial membrane-like structures has been described previously only in association with breast implants, the bone-cement interface of hip prostheses, tendon implants, testicular implants, and traumatized skin. Previous investigators have theorized that this phenomenon-referred to as "synovial metaplasia"-develops in response to gliding trauma. In some cases, these lesions can exhibit a papillary growth pattern. We report 2 unusual cases of oral mucoceles exhibiting papillary synovial metaplasia-like change: the first arising in the lower lip of an 11-year old African-American boy and the second in the lower lip of a 12-year-old European-American girl. We propose that these cases represent a rare and previously undescribed histopathologic variant of the oral mucocele. These lesions should be distinguished from other oral lesions that may exhibit a papillary cystic growth pattern.

Pseudomembranous disease (ligneous inflammation) of the female genital tract, peritoneum, gingiva, and paranasal sinuses associated with plasminogen deficiency.

Pseudomembranous disease (or ligneous inflammation) is a rare condition characterized by accumulations of fibrin-rich eosinophilic material. Recent investigations have linked the etiology of this condition to plasminogen deficiency (hypoplasminogenemia). Although much of the literature concerning this disease has focused upon the often clinically striking ocular manifestations, it is important to note that pathologic changes may develop in a variety of anatomic locations, including the oral cavity, upper and lower respiratory tract, female genital tract, kidneys, and gastrointestinal tract. Here, we report an unusual case of a 33-year-old woman who initially presented with gingival inflammation. In subsequent years, she developed additional signs and symptoms related to sinonasal and genital tract involvement. Despite numerous clinical evaluations, biopsies, and laboratory tests, the patient's diagnosis remained elusive for 7 years. Ultimately, it was the distinctive appearance of the gingiva that led to a diagnosis of plasminogen deficiency. Unfortunately, the complicated clinical course and elapsed time between initial presentation and diagnosis illustrated by the present case are not uncommon among patients with this condition. Greater familiarity with the clinical and histopathologic features of this condition among pathologists and treating clinicians is essential for timely diagnosis and management.

Ovarian mucinous tumors associated with mature cystic teratomas: morphologic and immunohistochemical analysis identifies a subset of potential teratomatous origin that shares features of lower gastrointestinal tract mucinous tumors more commonly encountered as secondary tumors in the ovary.

Most primary ovarian mucinous tumors are of surface epithelial-stromal origin and exhibit diffuse expression of cytokeratin 7 (CK7) combined with variable expression of cytokeratin 20 (CK20); this immunoprofile distinguishes them from most lower gastrointestinal tract tumors secondarily involving the ovaries. The uncommon ovarian mucinous tumors of germ cell (teratomatous) origin have not been extensively evaluated to determine the utility of these markers and other markers of intestinal differentiation for distinguishing these tumors from metastatic gastrointestinal tract mucinous tumors. Immunohistochemical expression of CK7, CK20, CDX2, and villin was assessed in 44 ovarian mucinous tumors associated with a mature cystic teratoma. All cases lacked evidence of a nonovarian primary mucinous tumor. All mucinous tumors were unilateral; 6 cases had bilateral teratomas. All tumors displayed gastrointestinal-type mucinous differentiation, with epithelium that was commonly goblet cell-rich or hypermucinous; 21 were associated with pseudomyxoma ovarii and 3 of these had pseudomyxoma peritonei. Tumor architecture ranged from purely cystadenomatous (n=24), to proliferative (n=13), to carcinomatous (n=6); some tumors had admixtures of these patterns. One tumor had a goblet cell carcinoidlike pattern with pseudomyxoma ovarii. Three carcinomas had a signet ring cell component. Cystadenomatous tumors without pseudomyxoma ovarii (n=15) exhibited all possible CK7/CK20 coordinate expression profiles with nearly equal frequency. All proliferative tumors without pseudomyxoma ovarii (n=8) expressed CK7, most often in combination with CK20 expression. All cystadenomatous and proliferative tumors with pseudomyxoma ovarii (n=9 and n=5) were CK7-/CK20+. All carcinomatous tumors had pseudomyxoma ovarii; 3 were CK7-/CK20+, 2 were CK7+/CK20+, and 1 was CK7+/CK20-. The presence of pseudomyxoma ovarii was significantly associated with a CK7-/CK20+ profile (86% with pseudomyxoma ovarii vs. 13% without, P<0.0001), CDX2 positivity (79% vs. 0%, P<0.0001), and villin positivity (57% vs. 5%, P=0.0009). A subset of mucinous tumors associated with mature cystic teratomas exhibiting morphologic and immunohistochemical features of lower intestinal tract-type mucinous tumors may be teratomatous in origin. In practice, the more common diagnosis of secondary involvement by a lower intestinal tract mucinous tumor should be addressed in the pathology report and in subsequent clinical evaluation; interpretation as a true primary ovarian mucinous tumor of teratomatous origin can be considered as an alternative diagnosis when evaluation and follow-up fail to identify a nonovarian source of the mucinous tumor. Those tumors having CK7 expression with or without CK20 expression may be derived from upper gastrointestinal tract-type or sinonasal-type teratomatous elements but could be independent tumors of surface epithelial-stromal origin.