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A study of immunohistopathologic and cytohistopathologic changes of the parabasal/basal layers in the differentiated squamous intraepithelial neoplasia (DSIN) may elucidate the histopathogenesis and reveal changes aiding early diagnosis and grading of the lesion.A total of 55 consecutive resection specimens of nonbasaloid squamous cell carcinoma of the anterior oral cavity and 8 biopsies before resections displaying DSIN in the overlying squamous epithelium were examined.Squamous epithelium that is continuous/immediately adjacent to invasive squamous cell carcinoma (type 1) and the more peripheral (type 2) epithelium of resection specimens displayed consistent changes in the parabasal/basal layers: (A) cytologic atypia with proliferation of parabasal cells with downward expansion causing reactive proliferation of the basal cell layer in the early stage, invading the basal layer in the late stage; (B) disordered nuclear/cytoplasmic arrangement; (C) "Cobblestone" appearance. Immunoreactivity for TP53 and Ki67 was helpful in the diagnosis. The epithelial spectrum of changes decreased as one moved from type 1 to type 2 lesions. Five out of 8 biopsies showed type 1 lesions (followed by resection in a period of 11±6 mo) and 3 showed type 2 lesions (followed by resection in a period of 55±20 mo). In addition, resections were margin positive for type 2 lesions in 5 cases associated with recurrence at the site of resection during a period of 69±9 months.DSIN is characterized by a proliferation of neoplastic parabasal cells with dyskeratosis, downward expansion/pushing of the basal layer with elongation of rete ridges. We proposed grading of DSIN based on the changes of the parabasal/basal layers.

Traumatic aneurysms of intracranial arteries are rare, forming less than 1% of all intracranial arteries. They may be associated with penetrating and non-penetrating trauma. Most cases are associated with fracturing of the skull. Rupture of traumatic aneurysms occur in up to 50% of cases and are typically delayed from days to weeks following the initiating trauma. We report a case of a 22-year-old man who was punched to the head. He was rendered unconscious but recovered and had a GCS of 14 on admission. CT scans showed subarachnoid hemorrhage. An initial angiogram was negative but on day 7 following the incident he was noted to have a 1 mm aneurysm of the posterior inferior cerebellar artery on CT angiogram. On day 9 he collapsed and was found to have new subarachnoid hemorrhage and to have a 4.0 mm × 3.7 mm. He did not recover and was declared brain dead on day 12. At autopsy, there was a 4.0 mm aneurysm of the left PICA just after the origin of the artery. Histological examination confirmed the presence of a traumatic false aneurysm in the left PICA. This case study shows sequential radiological imaging with pathologiocal correlation.

We hypothesize that cystic structures in metastatic papillary thyroid carcinoma (PTC) develop along the framework of lymphatic channels. To investigate this phenomenon, different categories of PTC were immunostained for D2-40 and TTF1. In this study, reactivity for D2-40 was considered as positive when there is membranous staining as often seen in lymphatic endothelial cells. Thirty cases of PTC with lymph node metastasis or with potential for lymphatic invasion and 20 cases metastatic PTC in lymph nodes were reviewed and found to show double/mosaic immunoreactivity for TTF1/D2-40 in 40-100% of cases. PTC metastasis in lymph nodes with cysts and some branching lymphatic-like channels lined by follicular cells with or without nuclear features of PTC were diffusely reactive to TTF1, and focally to D2-40. For primary and metastatic PTC, focal membranous D2-40 reactivity was also demonstrated in cysts or cleft linings. For25 thyroid neoplasms with no known potential for lymphatic invasion, there was no such immunoreactivity. The mosaic or double immunoreactivity for TTF1/D2-40 suggests lymphatic cancerization and possible endothelial mimicry of follicular cells. Mosaic/double immunoreactivity is helpful to detect the hidden pattern of lymphatic invasion masquerading as 'benign-appearing' follicles and supports our hypothesis of malignant cells developing along the lymphatic framework.

Background: Angiosarcomas (AS) are high-grade sarcomas that comprise less than 1% of soft tissue sarcomas. We compared clinical, pathological and molecular features of primary and recurrent conventional AS, including cases occurring in unusual backgrounds, such as organ transplants, at a site of metal orthopedic implant, and at a site of prior trauma. Materials and Methods: Paraffin blocks from 15 patients with AS were retrieved from our archives. Ten patients had recurrent AS, 4 patients had metastases. AS were morphologically categorized them into epithelioid and conventional types. Immunohistochemical stains included three vascular markers, cytokeratins, Akt, Ki67, HHV8 and EBV in paired samples of primary and recurrent/metastatic AS. Fluorescence In Situ Hybridization (FISH) analysis for Epidermal Growth Factor Receptor (EGFR) and Hepatocyte Growth Factor Receptor (MET) was performed on all AS samples. Results: Conventional AS were positive for more than two vascular markers and negative for cytokeratins. Epithelioid AS demonstrated variable positivity for vascular markers and cytokeratins. All tumors were negative for HHV8 and EBV. All AS displayed cytoplasmic immunopositivity for the phosphorylated forms of Akt. Conclusion: AS with epithelioid features had fewer positive vascular markers, possibly reflecting a lack of differentiation. There were no differences in pattern of immunoreactivity between post-transplant and conventional AS and primary and metastatic AS. No amplification of either EGFR or MET was found but a majority of the cases demonstrated hyperploidy and three cases demonstrated monosomy for EGFR in greater than 50% of cells. Both MET and EGFR are located on chromosome 7 and the detected hyperploidy and monosomy of these two genes are likely related to copy number alterations of chromosome 7. It is unlikely that these two genes play a role in biology of AS. AS with epithelioid features and metal associated AS, which are extremely rare, had an aggressive clinical course.

Introduction. Mapping of different foci in multifocal papillary thyroid carcinoma (PTC) has previously not been done as it is difficult to do so when thyroid specimens are serially sectioned transversely (ie, parallel to the horizontal plane). In this study, thyroidectomy specimens were serially sectioned coronally (ie, parallel to the largest surface of the thyroid gland), which allows for panoramic and 3-dimensional visualization of PTC foci and their relationship to one another. Materials and methods. A total of 125 consecutive total thyroidectomies or lobectomies followed by completion thyroidectomies were serially sectioned coronally and reviewed with identification and characterization of PTC foci. PTCs were grouped into either discrete, encapsulated nodule(s) (EN) of both follicular or papillary architecture, usual variant (UV), or tall cell variant (TCV). Results. The predominant tumor masses were identified in the right lobe, isthmus, and left lobe in 52%, 8%, and 40%, respectively. The largest tumor nodules ranged from 3 to 60 mm (18.8 ± 6.6) with the UV, EN, and TCV groups accounting for 58%, 24%, and 18% of cases, respectively. Three topographic patterns of PTC can be distinguished as follows: ( a) single tumor nodule (37 cases), ( b) main tumor nodule with satellite nodule(s) displaying no or varying degrees of fusion with the main one (30 cases), and ( c) main tumor nodule with either a second large nodule or randomly occurring tumor nodules (58 cases). Bilaterality can be seen in all 3 patterns but was most prevalent in the group comprising the main tumor nodule with either a second large nodule or random tumor nodules. It was least frequent in the EN group without random tumor nodules. The difference in rates of bilaterality between tumors

Signet ring cell (mucin producing) adenocarcinoma is a rare low grade salivary gland malignancy. While currently designated as an adenocarcinoma, myoepithelial differentiation has been implied in previously reported cases. We herein perform a survey of our cases of signet ring cell adenocarcinoma and review the literature in order to refine categorization of this rare tumor. Five cases were retrieved. One was reclassified as a mammary analogue secretory carcinoma, leaving four that fulfilled the criteria for signet ring cell adenocarcinoma: the presence of prominent signet ring or vacuolated cells arranged in islands, interconnecting strands, cords or sheets in a myxoid or hyaline stroma, or pools of mucin. An extensive panel of histochemical and immunohistochemical stains and fluorescence in situ hybridization (FISH) (modeled after common phenotypes and molecular alterations seen in signet ring and myoepithelial tumors at other sites) was performed. The male-to-female ratio was 3:1. The mean age was 56 years (range 18–81). Sites involved included buccal mucosa (2), soft palate (1) and deep parotid (1). Perineural and angiolymphatic invasion were present in three and two cases respectively. One patient was lost to follow up and the remainder were alive and without disease at time of last follow up (mean 38 months). All cases showed mucicarmine positive vacuolated/signet ring cells embedded in a myxoid stroma. Three cases showed at least focal p63 staining and two cases showed positivity for calponin. Membranous E-cadherin was retained in all cases. FISH was negative for ETV6, EWSR1, and ALK1 rearrangements in all four cases. Based on the current series and the previously reported cases, it is evident that signet ring adenocarcinomas have a dual secretory and myoepithelial phenotype and thus as a whole more appropriately designated as ‘secretory myoepithelial carcinoma.’ They behave in a fairly indolent fashion and do not share the major molecular alterations seen in other signet ring and myoepithelial tumor types.

A 67-year-old woman with a history of breast cancer presented with a soft tissue mass at the site of a remote, non-neoplastic lumbar surgery. Excisional biopsy revealed a traumatic neuroma. Five years later she re-presented with a rapidly growing, tender nodule at the same site. An excisional biopsy was again performed and revealed a tumor composed of malignant epithelioid and spindle cells merging imperceptibly with residual traumatic neuroma. The malignant cells were positive for vimentin, S-100 and micropthalmia transcription factor. They were negative for cytokeratins, muscle markers, Melan-A, HMB45, glial fibrillary acidic protein, and myelin basic protein. Electron microscopy showed no melanosomes. The diagnosis of malignant peripheral nerve sheath tumor arising within a long-standing traumatic neuroma was rendered and represents a hitherto unreported origin of this rare, aggressive soft tissue sarcoma.

Positive margins are associated with poor prognosis among patients with oral tongue squamous cell carcinoma (SCC). However, wide variation exists in the margin sampling technique.To determine the effect of the margin sampling technique on local recurrence (LR) in patients with stage I or II oral tongue SCC.A retrospective study was conducted from January 1, 1986, to December 31, 2012, in 5 tertiary care centers following tumor resection and elective neck dissection in 280 patients with pathologic (p)T1-2 pN0 oral tongue SCC. Analysis was conducted from June 1, 2013, to January 20, 2015.In group 1 (n = 119), tumor bed margins were not sampled. In group 2 (n = 61), margins were examined from the glossectomy specimen, found to be positive or suboptimal, and revised with additional tumor bed margins. In group 3 (n = 100), margins were primarily sampled from the tumor bed without preceding examination of the glossectomy specimen. The margin status (both as a binary [positive vs negative] and continuous [distance to the margin in millimeters] variable) and other clinicopathologic parameters were compared across the 3 groups and correlated with LR.Local recurrence.Age, sex, pT stage, lymphovascular or perineural invasion, and adjuvant radiation treatment were similar across the 3 groups. The probability of LR-free survival at 3 years was 0.9 and 0.8 in groups 1 and 3, respectively (P = .03). The frequency of positive glossectomy margins was lowest in group 1 (9 of 117 [7.7%]) compared with groups 2 and 3 (28 of 61 [45.9%] and 23 of 95 [24.2%], respectively) (P .001). Even after excluding cases with positive margins, the median distance to the closest margin was significantly narrower in group 3 (2 mm) compared with group 1 (3 mm) (P = .008). The status (positive vs negative) of margins obtained from the glossectomy specimen correlated with LR (P = .007), while the status of tumor bed margins did not. The status of the tumor bed margin was 24% sensitive (95% CI, 16%-34%) and 92% specific (95% CI, 85%-97%) for detecting a positive glossectomy margin.The margin sampling technique affects local control in patients with oral tongue SCC. Reliance on margin sampling from the tumor bed is associated with worse local control, most likely owing to narrower margin clearance and greater incidence of positive margins. A resection specimen-based margin assessment is recommended.

The number of reported cases of smooth muscle tumor (SMT) arising in patients with AIDS has been increasing since the mid-1990s. The aim of this study is to characterize the epidemiology, clinical manifestations, pathologic features, prognosis and, management of Epstein-Barr virus-related SMT (EBV-SMT) in patients with AIDS. An English language literature search identified 53 articles including 64 reported cases of EBV-SMT. The majority of these reports involved patients who were young, severely immunosuppressed, and had multifocal tumors. The central nervous system was the most common site to be involved. Histologically, tumors had smooth muscle features and were immunoreactive for muscle markers and all but two tumors demonstrated the presence of EBV by either immunohistochemistry, in situ hybridization, and/or PCR. While mitoses and/or necrosis were used to separate leiomyoma from leiomyosarcoma, these features did not correlate with clinical outcome. Treatment included primarily resection, and less often radiotherapy, chemotherapy and highly active antiretroviral therapy (HAART). Overall, EBV-SMTs appear to have variable aggressiveness and clinical outcome and may exhibit a more favorable prognosis compared to conventional leiomyosarcoma. Tumor-related death from EBV-SMT occurred in only 4 of 51 patients.

3109 Background: This study investigates the prognostic value of overexpression of EGFR, HER2 and c-Met by immunohistochemistry (IHC) in Canadian patients with GC and correlates expression with cli...

The presence of a solitary, firm, progressive or rapidly growing mass in the orofacial region has a long list of differential diagnoses, ranging from benign lesions to more fatal malignant ones. Nodular fasciitis (NF) is a benign, reactive proliferation of fibroblasts and myofibroblasts, which typically arises in the subcutaneous fascia, most probably in response to a local injury. Although commonly seen in the upper extremities (50%), orofacial NF is less common, with an incidence of less than 20%, primarily affecting adults in the fourth and fifth decades of their life. In this report, we describe a unique case of oronasal nodular fasciitis, aggravated by trauma, in a six-year-old female child. To the best of our knowledge, this is the first case report in the literature of nodular fasciitis arising in this anatomic location.

Erdheim–Chester disease (ECD) is a rare, multisystem disorder of macrophages. Patients manifest with histiocytic infiltrates that lead to xanthogranulomatous lesions in multiple organ systems. The cytologic features of this disorder are not well characterized. As a result, the cytologic diagnosis of ECD can be very challenging. The aim of this report is to describe the cytomorphology of ECD in a patient presenting with a retroperitoneal soft tissue lesion. A 54-year-old woman with proptosis and diabetes insipidus was found on imaging studies to have multiple intracranial lesions, sclerosis of both femurs and a retroperitoneal soft tissue mass. Fine needle aspiration (FNA) and a concomitant core biopsy of this abnormal retroperitoneal soft tissue revealed foamy, epithelioid and multinucleated histiocytes associated with fibrosis. The histiocytes were immunoreactive for CD68, CD163, Factor XIIIa and fascin, and negative for S100, confirming the diagnosis of ECD. ECD requires a morphologic diagnosis that fits with the appropriate clinical context. This case describes the cytomorphologic features of ECD and highlights the role of cytology in helping reach a diagnosis of this rare disorder.

Background Burkitt lymphoma is a high-grade B cell lymphoma which accounts for less than 1% of all adult cases of non-Hodgkin lymphoma. Rare instances of Burkitt lymphoma developing secondary to prior irradiation have been described in the literature. Case presentation We report a case of a 90-year-old white woman with a recent history of irradiation for Hodgkin lymphoma, who presented with primary Burkitt lymphoma of the supraglottic larynx. She underwent emergency awake tracheostomy with biopsy. A histopathological examination confirmed non-Hodgkin, B cell lymphoma of Burkitt type. Given her age and poor functional status, she underwent treatment with palliative radiotherapy. Conclusions A literature review was performed to clarify the clinical characteristics of radiation-induced Burkitt lymphoma in the head and neck, as well as its diagnosis and management. The present case represents the second case of radiation-induced Burkitt lymphoma in the head and neck in the reported literature, and the first in the supraglottic larynx. It highlights the need to maintain a broad differential in the assessment of malignancies of the larynx, particularly in patients with a prior history of radiation treatment.