Irregular Nests Research Articles

Stromal and Epithelial Architectural Alterations Mimicking Invasion (Pseudoinvasion) in Noninvasive Papillary Urothelial Carcinoma.

Retraction artifact, paradoxic maturation/differentiation, desmoplasia, and complex irregular growth are morphologic criteria of invasion in urothelial carcinoma. To describe changes mimicking invasion in noninvasive papillary urothelial carcinoma (NPUC). We reviewed 159 consecutive in-house patients with NPUC for either the presence of pseudoinvasion (irregular carcinoma nests within dense hyalinized stroma in the absence of other criteria of invasion) or precursor findings (stromal hyalinization not yet associated with epithelial architectural alteration). We assessed the correlation of these findings with age, sex, evidence of peripheral vascular disease, tumor grade, tumor infarction, and tumor size. We then followed up the patients clinically for tumor recurrence or progression. We identified 233 separate NPUCs (136 high grade and 97 low grade) in 125 men and 34 women. Of the 233 tumors, 26 (11.2%) had pseudoinvasion and 24 of 233 tumors (10.3%) had precursor findings. Except for complex irregular growth, no other criteria for invasion were seen. Pseudoinvasion and precursor findings were more common in men (47 of 183 [26%] versus 3 of 50 [6%]; P = .003), larger tumors (mean size, 2.6 versus 1.2 cm; P < .001), and tumors with infarction (33 of 50 [66%] versus 29 of 183 [15.8%]; P < .001). In multivariable analysis, tumor size (odds ratio, 1.49; P =.006), male sex (odds ratio, 6.48; P = .007), and the presence of infarction (odds ratio, 6.59; P < .001) were significant variables. Recurrence rates did not differ between patients with and those without pseudoinvasion (31% [5 of 16] versus 42% [45 of 107], respectively; P = .41). None of the tumors with pseudoinvasion progressed to invasive carcinoma. Given the correlation with size and presence of infarcted papillae, we suggest the possibility of tumor ischemia/infarction as a plausible etiology of pseudoinvasion. Awareness of this phenomenon is important for the accurate diagnosis of invasion in papillary urothelial carcinoma.

Keratocystoma: A Distinctive Salivary Gland Neoplasm Characterized by RUNX2 Rearrangements.

Keratocystoma is a rare salivary gland lesion that has been reported primarily in children and young adults. Because of a scarcity of reported cases, very little is known about it, including its molecular underpinnings, biological potential, and histologic spectrum. Purported to be a benign neoplasm, keratocystoma bears a striking histologic resemblance to benign lesions like metaplastic Warthin tumor on one end of the spectrum and squamous cell carcinoma on the other end. This overlap can cause diagnostic confusion, and it raises questions about the boundaries and definition of keratocystoma as an entity. This study seeks to utilize molecular tools to evaluate the pathogenesis of keratocystoma as well as its relationship with its histologic mimics. On the basis of targeted RNA sequencing (RNA-seq) results on a sentinel case, RUNX2 break-apart fluorescence in situ hybridization (FISH) was successfully performed on 4 cases diagnosed as keratocystoma, as well as 13 cases originally diagnosed as tumors that morphologically resemble keratocystoma: 6 primary squamous cell carcinomas, 3 metaplastic/dysplastic Warthin tumors, 2 atypical squamous cysts, 1 proliferating trichilemmal tumor, and 1 cystadenoma. RNA-seq and/or reverse transcriptase-PCR were attempted on all FISH-positive cases. Seven cases were positive for RUNX2 rearrangement, including 3 of 4 tumors originally called keratocystoma, 2 of 2 called atypical squamous cyst, 1 of 1 called proliferating trichilemmal tumor, and 1 of 6 called squamous cell carcinoma. RNA-seq and/or reverse transcriptase-PCR identified IRF2BP2::RUNX2 in 6 of 7 cases; for the remaining case, the partner remains unknown. The cases positive for RUNX2 rearrangement arose in the parotid glands of 4 females and 3 males, ranging from 8 to 63 years old (mean, 25.4 years; median, 15 years). The RUNX2 -rearranged cases had a consistent histologic appearance: variably sized cysts lined by keratinizing squamous epithelium, plus scattered irregular squamous nests, with essentially no cellular atypia or mitotic activity. The background was fibrotic, often with patchy chronic inflammation and/or giant cell reaction. One case originally called squamous cell carcinoma was virtually identical to the other cases, except for a single focus of small nerve invasion. The FISH-negative case that was originally called keratocystoma had focal cuboidal and mucinous epithelium, which was not found in any FISH-positive cases. The tumors with RUNX2 rearrangement were all treated with surgery only, and for the 5 patients with follow-up, there were no recurrences or metastases (1 to 120 months), even for the case with perineural invasion. Our findings solidify that keratocystoma is a cystic neoplastic entity, one which appears to consistently harbor RUNX2 rearrangements, particularly IRF2BP2::RUNX2 . Having a diagnostic genetic marker now allows for a complete understanding of this rare tumor. They arise in the parotid gland and affect a wide age range. Keratocystoma has a consistent morphologic appearance, which includes large squamous-lined cysts that mimic benign processes like metaplastic Warthin tumor and also small, irregular nests that mimic squamous cell carcinoma. Indeed, RUNX2 analysis has considerable promise for resolving these differential diagnoses. Given that one RUNX2 -rearranged tumor had focal perineural invasion, it is unclear whether that finding is within the spectrum of keratocystoma or whether it could represent malignant transformation. Most important, all RUNX2 -rearranged cases behaved in a benign manner.

Melanocytic Lesions with Peripheral Globules: Proposal of an Integrated Management Algorithm.

A peripheral rim of globules represents a marker of the horizontal growth phase in nevi and is a common feature in children and adolescents. The observation of melanocytic lesions with peripheral globules (MLPGs) in adulthood deserves more attention, since melanoma may exhibit this feature, albeit rarely. Risk-stratified management recommendations considering a global clinical approach are still missing. To analyze current knowledge on MLPGs and propose an integrated management algorithm stratified for age groups. We conducted a narrative review of current published data on MLPGs, analyzing clinical dermoscopic and confocal distinguishing features of melanoma from benign nevi. The risk of finding a melanoma when removing an MLPG increases with age, especially in people >55 years old, and is significantly higher in the extremities, head/neck and in case of a single asymmetrical lesion, ≥6 mm in diameter. Dermoscopic features associated with melanoma diagnosis include atypical peripheral globules, asymmetrical distribution, multiple rims as well as the reappearance of globules after prior loss. In addition, wide blue-grey regression areas, atypical networks, eccentric blotches, tan structureless peripheral areas and vascularization are atypical dermoscopic features. Confocal worrisome findings are represented by pagetoid cells within the epidermis, architectural disarrangement and atypical cells of the dermo-epidermal junction with irregular peripheral nests. We proposed a multi-step age-stratified management algorithm integrating clinical, dermoscopic and confocal findings that may increase the early recognition of melanoma and avoid surgical excision of benign nevi.

Epithelioid hemangioendothelioma mimicking aortic intramural haematoma.

A 69-year-old man presented with a dull chest pain for 2 months. He denied history of hypertension or trauma. Computed tomography angiography (CTA) indicated ‘intramural haematoma’ in descending aorta (Panel A). Control blood pressure and heart rate were as follows: target 120/70 mm/Hg, 60 beats/min, and the patient was discharged. One month later, to check the progression of aortic intramural haematoma, CTA was done (Panel B). The intramural haematoma area is larger than before. Positron emission tomography/computed tomography (PET/CT) was done for the enlarged area of intermural haematoma without clinical manifestation. PET/CT revealed abnormal intense high metabolic region around aorta (Panel C) and a similar hypermetabolic mass in right lower kidney (Panel D), as well as abdominal lymph node metastasis. For histologic confirmation, biopsy of the renal mass was obtained, and pathological studies supported the diagnosis of epithelioid haemangioendothelioma. The pathologic finding showed irregular nests of atypical epithelioid cells with intracytoplasmic vacuoles (Panel E, arrow). The tumour cells are immunoreactive to ETS-related gene (Panel F). The final diagnosis was made as epithelioid haemangioendothelioma around aortic with multiple metastasis. Our patient died <6 months after the diagnosis was made.

Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques.

Administration of a novel and selective small molecule integrin αvβ6 inhibitor, MORF-627, to young cynomolgus monkeys for 28 days resulted in the rapid induction of epithelial proliferative changes in the urinary bladder of 2 animals, in the absence of test agent genotoxicity. Microscopic findings included suburothelial infiltration by irregular nests and/or trabeculae of epithelial cells, variable cytologic atypia, and high mitotic rate, without invasion into the tunica muscularis. Morphologic features and patterns of tumor growth were consistent with a diagnosis of early-stage invasive urothelial carcinoma. Ki67 immunohistochemistry demonstrated diffusely increased epithelial proliferation in the urinary bladder of several monkeys, including those with tumors, and αvβ6 was expressed in some epithelial tissues, including urinary bladder, in monkeys and humans. Spontaneous urothelial carcinomas are extremely unusual in young healthy monkeys, suggesting a direct link of the finding to the test agent. Inhibition of integrin αvβ6 is intended to locally and selectively block transforming growth factor beta (TGF-β) signaling, which is implicated in epithelial proliferative disorders. Subsequent in vitro studies using a panel of integrin αvβ6 inhibitors in human bladder epithelial cells replicated the increased urothelial proliferation observed in monkeys and was reversed through exogenous application of TGF-β. Moreover, analysis of in vivo models of liver and lung fibrosis revealed evidence of epithelial hyperplasia and cell cycle dysregulation in mice treated with integrin αvβ6 or TGF-β receptor I inhibitors. The cumulative evidence suggests a direct link between integrin αvβ6 inhibition and decreased TGF-β signaling in the local bladder environment, with implications for epithelial proliferation and carcinogenesis.

A Unique Case of Squamous Cell Carcinoma Presenting Within a Lesion of Granuloma Annulare

Granuloma annulare (GA) is a common benign granulomatous inflammatory disorder of the dermis or subcutis with classic morphologic and histologic presentation. Common clinical subtypes of granuloma annulare include localized, generalized, subcutaneous, perforating, and patch types. A biopsy is critical in cases of granuloma annulare with atypical features. We present a case of a 58-year-old male who presented with an annular scaly erythematous plaque on the right dorsal hand. Shave biopsy demonstrated irregular nests of mildly atypical squamous epithelium present within the superficial dermis, with abundant histiocytes and multinucleated giant cells arranged in palisades peripherally. These findings were consistent with invasive well-differentiated squamous cell carcinoma (SCC) with surrounding granuloma annulare. This case highlights a unique presentation in which clinicopathologic correlation is critical prior to arriving at a correct diagnosis.

Incidental Colonic Ganglioneuroma on Surveillance Colonoscopy.

CASE REPORT A 73-year-old man with a history of diverticulitis after left hemicolectomy and an end-to-end colo-colonic anastomosis underwent a screening colonoscopy with resection of 4, 2-10-mm tubular adenomas. A 10-mm semipedunculated polyp with a normal mucosal pit pattern under narrow-band imaging was found in the splenic flexure (Figure 1). The polyp was resected using a hot snare and submitted for histopathological diagnosis, which demonstrated colonic mucosa with distorted crypt architecture. The lamina propria was expanded by collection of spindle cells within fibrillary matrix, and irregular nests and groups of ganglion cells indicated a ganglioneuroma (GN) (Figure 2). No clinical symptoms were associated with this finding, and a prior colonoscopy revealed no evidence of GN. Surveillance colonoscopy was recommended in 3 years, given the presence of an adenoma of ≥10 mm in size.Figure 1.: (A) A semipedunculated polyp under white-light imaging in the splenic flexure. (B) A semipedunculated polyp with a normal mucosal pit pattern under narrow-band imaging in the splenic flexure.Figure 2.: (A) An (H&E original magnification 20×) image of the colonic polyp consisting of abnormal appearing ganglion cells (single arrow) and spindled Schwann cells (double arrows). (B) An (H&E original magnification 10×) image of the colonic polyp consisting of abnormal appearing ganglion cells and spindled Schwann cells. H&E, hematoxylin & eosin.Ganglioneuromas of the gastrointestinal tract are rare tumors composed of ganglion cells, nerve fibers, and supporting cells. Gastrointestinal GNs are usually confined to the large intestine and are morphologically classified into 3 categories, namely, polypoid GNs, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis.1 Polypoid GNs are mostly solitary and small (measuring <20 mm), with a sessile or pedunculated appearance. Colonic GNs are characterized by a normal colonic pit pattern under narrow-band imaging. These lesions produce no characteristic symptoms and are usually found incidentally during endoscopy. Rarely, they present with abdominal pain, obstruction, ileus, appendicitis, or weight loss depending on their size and anatomical location.2 Ganglioneuromatous polyposis and diffuse ganglioneuromatosis are associated with genetic syndromes, such as neurofibromatosis 1, multiple endocrine neoplasia 2B syndrome, and juvenile polyposis. Solitary GNs are generally not associated with familial syndromes, although they have been reported in cases of Cowden disease, tuberous sclerosis, polyposis coli, and juvenile polyposis.1 Gastrointestinal GNs are usually treated with endoscopic resection. Currently, no guidelines exist on the management of solitary GNs or recommendations for interval surveillance colonoscopy. Repeat colonoscopy is not necessary because of the benign nature of these lesions, which tend not to recur.3 DISCLOSURES Author contributions: S. Agarwal and Y. Wang designed and drafted the article and acquired data. PG Iyer drafted and revised the article for intellectual content. CL Leggett designed and drafted the article , acquired data, revised the article for important intellectual content, and is the article guarantor. Financial disclosure: None to report. Informed patient consent was obtained for this case report.

A case of spontaneous rete testis adenoma in a Sprague–Dawley rat

A 104-week-old male CD (SD) rat exhibited enlargement of the left testis. Microscopically, this mass was demarcated from the testis by fibrous connective tissue and characterized by cystic dilatation with single-layered columnar cells and papillary proliferation connected to the solid growth area without clear boundaries. In the solid growth area, cells were dissected into irregular alveolar nests by scant fibrous tissue with small blood vessels. The nuclei of proliferating cells were variable in size and round- to oval-shaped, and their cytoplasm was pale or eosinophilic and sometimes contained vacuoles or eosinophilic granules. Immunohistochemically, the tumor cells were positive for vimentin and cytokeratin (CK) 7. Since CK7 was exclusively positive in the rete testis epithelium of the naïve rat, it was valuable to diagnose this tumor as rete testis-originated. Based on these results and the lack of apparent pleomorphism, mitotic figures, and metastasis, the present case was diagnosed as rete testis adenoma.

Regional Ranking of Marine Turtle Nesting in Remote Western Australia by Integrating Traditional Ecological Knowledge and Remote Sensing

Western Australia’s remote Kimberley coastline spans multiple Traditional Owner estates. Marine turtle nesting distribution and abundance in Indigenous Protected Areas and newly declared Marine Parks were assessed by aerial photogrammetry surveys for the Austral summer and winter nesting seasons. Images of nesting tracks were quantified in the lab and verified by ad hoc ground patrols. The rankings of log-scaled plots of track abundance and density give guidance to regional co-management planning. Spatial and temporal differences were detected in that remoter islands had higher nesting usage and few terrestrial predators. The surveys found year-round green turtle nesting peaking in summer, as well as spatial boundaries to the summer and winter flatback stocks. Summer surveys recorded 126.2 island activities per km and 17.7 mainland activities per km. Winter surveys recorded 65.3 island activities per km and quantified a known winter mainland rookery with 888 tracks/km. The three highest density rookeries were found to be winter flatback turtles at Cape Domett, summer green turtles at the Lacepede Islands and summer flatback turtles at Eighty Mile Beach. Moderate to lesser density nesting by summer green turtles and winter flatback turtles occurred in the North Kimberley offshore islands. Traditional Ecological Knowledge and ground-based surveys verified the harder-to-detect species (olive ridley or hawksbill turtles) with irregular nesting, low track persistence and non-aggregated nesting. Higher-density rookeries may provide locations for long-term monitoring using repeated aerial or ground surveys; however, the sparse or infrequently nesting species require insights gleaned by Tradition Ecological Knowledge. Common and conspicuous nesters are easily detected and ranked, but better-informed co-management requires additional ground surveys or surveys timed with the reproductive peaks of rarer species.

Melanocytic lesions with peripheral globules: results of an observational prospective study in 154 high-risk melanoma patients under digital dermoscopy follow-up evaluated with reflectance confocal microscopy.

The management of melanocytic lesions with peripheral globules (MLPGs) is usually age-dependent and can be challenging in high-risk melanoma patients. To evaluate clinical, dermoscopic and reflectance confocal microscopy (RCM) features of MLPG in patients under digital dermoscopic surveillance. To know whether dermoscopic or RCM findings correlate with histologic diagnosis and the accuracy of the dermoscopy-RCM compared with histopathology. During 24 months, we prospectively enrolled MLPG in patients under digital dermoscopy follow-up. All were evaluated by dermoscopy and RCM and excised for histologic examination. We enrolled 154 patients, mean age 42.45years (18.78-73.19). Three melanomas and 19 dysplastic naevi (DNs) were diagnosed. There were no significant differences in the age of the patients (P=0.662). MLPGs with diameter of 6mm or more and asymmetry in two axes were associated with melanoma (P=0.01, P=0.003). Patients with more than one MLPG were less likely to have melanoma. Blue-grey and red colours were more frequent in melanoma (P=0.013 and P=0.000). Different sizes and shapes of PG were associated with DN and melanoma (P=0.000 and P=0.001). In a new lesion, PG in <25% of the circumference was related to malignancy (P=0.010). RCM signs of malignancy were related to melanoma: pagetoid cells (P=0.000), non-edged papillae (P=0.001), atypical junctional thickenings (P=0.000) and atypical cells at the dermal-epidermal junction (P=0.000). Dense irregular nests were associated to melanoma (P=0.019). Dermoscopy and confocal evaluation were able to diagnose 100% of melanomas and 84.21% of DNs. The kappa coefficient between dermoscopy-RCM vs. histology was 0.76. We recommend to excise a MLPG when it presents asymmetry in two axes, 6 or more mm, new lesion with PG in less than the 25% of the circumference, irregular size and shape PGs and irregular dense nests on RCM, regardless of the patient's age.

Histopathology of recurrent Steel syndrome in fetuses caused by novel variants of COL27A1 gene.

Steel syndrome (STLS) encompasses characteristic facies, dwarfness, irreducible bilateral hip and radial head dislocation, and carpal bone coalition due to COL27A1 mutations. Two consecutive pregnancies in a non-consanguineous couple were terminated because of severe fetal anomalies. Complete autopsies with microscopic exam were performed on both fetuses. Next-generation-based clinical exome sequencing was applied to the first fetus. Exome sequencing results, parental segregation, and affection of the second fetus were confirmed by Sanger sequencing. Both fetuses had signs consistent with STLS. Bilateral capitulum humeri absence explained radial head dislocation in STLS. Metaphyseal cartilage showed severe disorganization. Resting cartilage was hypercellular, organized in irregular nests limited by acellular matrix. Two variants in COL27A1 (c.2548G>A -p.Gly850Arg- and c.3249+1G> T) were found in both fetuses in compound heterozygosity with parental Mendelian segregation. This is the first report to include histology of STLS. The COL27A1 variants here described increase the number of mutations associated with STLS.

S1774 Primary Anorectal Malignant Melanoma: Rare and Fatal

INTRODUCTION: We present an uncommon diagnosis of primary anorectal malignant melanoma (ARMM) in a patient with anemia and altered bowel habits. Primary ARMM accounts for less than 4% of anorectal malignancies and less than 1.5% of all melanomas. ARMM can often go undiagnosed, which is detrimental to patients due to its aggressive nature. CASE DESCRIPTION/METHODS: 63 y.o. African American male with a history of ascending colon resection for colon adenocarcinoma 8 years prior was referred for change in bowel habits and nausea with eating. He had worsening intermittent constipation, but denied melena or blood in his stool. He had nausea 45 minutes after eating but no vomiting. He denied recent weight loss. His last colonoscopy was a year after colon resection. The ileocolonic anastomosis was at 70 cm from anal verge, there was a 3 mm hyperplastic polyp in the sigmoid and repeat colonoscopy was recommended in a year. Physical exam was negative for skin hyperpigmentation, moles or lesions. Abdominal exam was negative for tenderness, guarding or rebound. Labs showed normocytic anemia, Hgb 8.1 g/dl from 12 g/dl the year prior. Digital rectal exam revealed a firm immobile mass, 3 cm from anal verge. Colonoscopy showed a fungating, ulcerated, non-obstructing 3 cm mass in the rectum. Biopsies were done with cold forceps for histology. Pathology noted the mass had brownish pigmentation and extensive necrosis, consistent with malignant melanoma. Immunohistochemical staining was positive for S-100, HMB-45, Melan-A and SOX-10 supporting the diagnosis. A diagnosis of primary anorectal malignant melanoma was made as patient had no evidence of cutaneous or ocular melanoma. PET scan showed metastasis to a large pelvic lymph node so patient was not a surgical candidate. Oncology started patient on immunotherapy with ipilmumab and nivolumab. DISCUSSION: Primary ARMM is a rare malignancy, especially in African Americans such as our patient, with a poor prognosis. As with our case, presenting symptoms can be unspecific such as anemia. Often patients with ARMM present with rectal bleeding that is attributed to hemorrhoids and endoscopic intervention is not pursued. This is detrimental as it causes a delay in diagnosis. Our patient’s mass was pigmented, but in 29% of cases the mass may be amelanotic resulting in misdiagnosis. Treatment is abdominoperineal resection if there is no evidence of metastasis. Our case highlights the importance of recognizing primary ARMM as a cause of rectal bleeding in patients with an anorectal mass.Figure 1.: Retroflexed view in the rectum revealing the pigmented, ulcerated, non-obstructing 3 cm mass at 3 cm from anal verge.Figure 2.: The mass is composed of melanoma cells that formed irregular nests and cords, and manifested enlarged and hyperchromatic nuclei with irregular nuclear contours and prominent nucleoli. The pigments were finely granular and brownish. (H&E, x200).Figure 3.: Immunohistochemistry demonstrated the tumor cells to be positive for S-100 (Fig. A, cytoplasmic stain, fast red; X100), HMB-45 (Fig. B, cytoplasmic stain, fast red; X100) and SOX-10 (Fig. D, nuclear stain, fast red; X100). They were negative for expression of pan-cytokeratin, the brown granules in the background are melanin pigments (Fig.C, AE1/3, lack of cytoplasmic stain, DAB; X100).

Clinicopathological features of composite pheochromocytoma

Objective: To detect the clinicopathological features, immunophenotype, diagnosis, and differential diagnosis of composite pheochromocytoma(CP). Methods: Five cases of CP were collected at Zhejiang Provincial People's Hospital from January 2011 to January 2019. The clinical, radiological, histologic, immunohistochemical and outcome data were analyzed; the diagnosis and differential diagnosis were discussed. Results: The patients' age range was 52-68 years (mean 59 years, median 54 years), There were 4 males and 1 female, and the male to female ratio was 4∶1. Tumor size was 3-4 cm (mean 3.6 cm, median 3.5 cm). The most common clinical manifestation was adrenal mass. Histologically, the classical feature was two distinct morphologic components, one with tumor cells arranged in irregular nests, and with fine granular and basophilic oramphophilic cytoplasm; the other was composed of scattered ganglion cells in the background of Schwann cells organized in interwoven bundles. The components of pheochromocytoma expressed PHOX2B(5/5), synaptophysin (5/5), CgA (5/5), the sustentacular cells expressed S-100 protein; the components of ganglioneuroma expressed S-100 protein (5/5), NF (5/5), the ganglion cells were weakly positive for PHOX2B, synaptophysin and CgA. All the cases were surgically resected and all patients were free of recurrence at follow-up. Conclusions: CP is rare adrenal tumor, and it has typical histologic features but no specific clinical manifestations. Attention should be paid to its characteristic histomorphology with the use of PHOX2B, CgA, synaptophysin and S-100 protein immunohistochemistry that is helpful for its diagnosis.

LOW-FAT SPINDLE CELL LIPOMA OF THE LOWER LIP: IMMUNOHISTOCHEMICAL ANALYSIS

A 29-year-old white man was referred for a nodular lesion on the lower lip. The lesion originated after trauma and gradually increased in volume for 2 months without symptomatology and cervical lymphadenopathy. Clinically, a sessile nodule covered by normal-appearing oral mucosa was observed. Surgical removal was performed, and microscopic analyses revealed scarce mature adipose tissue arranged in irregular small nests or single cells, supported by predominantly collagenous stroma, containing foci of wiry to ropey collagen. Spindled cells were arranged discreetly in short bundles surrounded by small blood vessels. No fibrous capsule surrounding the lesion was observed. To better characterize the lesion, a panel of immunohistochemistry was performed, which showed uniform and strong positivity for CD34 (endothelial and spindled cells), as well as reactivity for S100 (adipocytes) and α–smooth muscle actin (vessel walls). The patient's postoperative recovery showed no complications and no recurrence after 1.5 years of follow-up.

Establishment of a model of sentinel lymph node metastasis using immunodeficient swine

Lymph node metastasis occurs via the migration of cancer cells through the lymphatic system. Sentinel lymph node (SLN) biopsy is a common diagnostic strategy. SLNs have been studied using healthy rodents and large animals without metastasis. Here we used immunodeficient swine to establish a model of lymph node metastasis. We used RAG2-knockout immunodeficient swine. A431 human epithelial carcinoma cells expressing green fluorescent protein were injected subcutaneously into the posterior sides of the auricle, forelimb and hindlimb of knockout swine. Indigo carmine dye was injected subcutaneously 8 weeks after tumour cell transplantation. SLNs were extracted, observed using a stereoscopic fluorescence microscope and analysed histologically using haematoxylin and eosin staining, and immunohistochemistry. Lymphoid follicles were found in wild-type swine, and a few aggregated lymphocytes and immature lymphoid follicles were observed in knockout swine. Fluorescence in the lymph nodes indicated metastasis of tumour cells to the lymph nodes. Tumour cells replaced lymph node architectures, showed high-grade nuclear atypia and formed irregular tumour nests. Our model may be useful for the preclinical validation of diagnostic methods and minimally invasive treatment of metastatic cancer.

Phosphaturic mesenchymal tumor with an admixture of epithelial and mesenchymal elements in the jaws: clinicopathological and immunohistochemical analysis of 22 cases with literature review

Information on the heterogeneity of phosphaturic mesenchymal tumor, a rare entity associated with tumor-induced osteomalacia, is limited. In this retrospective analysis of 222 phosphaturic mesenchymal tumors, 22 cases exhibited mixed mesenchymal and epithelial elements, which we propose to term “phosphaturic mesenchymal tumor, mixed epithelial, and connective tissue type.” Phosphaturic mesenchymal tumor of the mixed epithelial and connective tissue type showed a distinctive and significant male predominance (male:female = 2.67:1), with most patients diagnosed at <40 years old. Moreover, all tumors were mainly located in the alveolar bone with focal invasion into surrounding soft tissue and oral mucosa, which could be detected preoperatively by oral examination. The mesenchymal component, composed of spindled cells resembling fibroblasts or myofibroblasts arranged in a storiform or fascicular pattern, exhibited a less prominent vasculature and lower cellularity than the typical phosphaturic mesenchymal tumor (mixed connective tissue type). The epithelial component was typically haphazardly and diffusely distributed throughout the tumor, forming small, irregular nests resembling odontogenic epithelial nests. All cases were immunoreactive for fibroblast growth factor-23, somatostatin receptor 2A, and NSE in both components. Mostly also demonstrated positive staining for CD99 (21/22, 96%), CD56 (16/22, 73%), Bcl-2 (21/22, 96%), and D2-40 (19/22, 86%) in one or both components. S100 was positive in both components in one of seven cases. Interestingly, immunoreactivity was typically stronger and more diffuse in the epithelial than in the paired mesenchymal components. The mesenchymal component was also diffusely positive for CD68 (17/17, 100%) and showed variable focal staining for SMA (15/22, 68%) and CD34 (9/19, 47 %). These results indicate that phosphaturic mesenchymal tumor of the mixed epithelial and connective tissue type has distinctive clinicopathological characteristics and a polyimmunophenotypic profile.

Massive parallelization accelerated solution for the 2D irregular nesting problem

One important field of operations research are the cutting and packing problems, which often have significant environmental and economical impacts and are reoccurring in the wood, textile and shipbuilding industry, among others. They consist of generating a layout of non-overlapping items which are bounded by a single or multiples larger objects, usually referred as containers. The bi-dimensional irregular nesting involves placing irregular shaped items inside a single rectangular container with variable length. Due to the geometric complexity, heuristic solutions are often employed to solve instances with more than a dozen items. Relaxing the overlap constraint is an efficient strategy to obtain more compact layout, however it is usually computationally costly. If the placement is restricted by a grid of points, known as the dotted board model, the overlap evaluation can be reduced to matrix operations, which can be accelerated by massive parallelization using the graphics processing unit (GPU). So as to aid the overlap evaluation and minimization, the obstruction map is adopted as a geometric tool to perform the guided local search. In this work, a parallel GPU implementation of the obstruction map is compared with the serial variant. Results show acceleration of over 10 times for cases with a very refined placement grid. Moreover, analysis of tests with 12 benchmark cases gives guidelines to determine whether it is beneficial to use the parallel implementation for a generic instance.

The Great grey Shrike Lanius excubitor L. of the Arrigoni degli Oddi’s ornithological collection at the Museo Civico di Zoologia, Rome (Italy)

[Lanius excubitor is a polymorphic species with 12 subspecies. In the last years the taxonomy of this species has been reviewed several times. According to the literature, in Italy Lanius excubitor is a regular migrator, wintering and irregular nesting, occurring with three subspecies: L. excubitor excubitor, L. e. homeyeri and L. e. sibiricus. This paper aims at reviewing the subspecies actually occurring in Italy by analyzing the specimens preserved in the Arrigoni degli Oddi’s collection at the Museo Civico di Zoologia in Rome (Italy). The morphometrics and colouring of 66 specimens were examined in relation to the most recent literature data. This review allowed to demonstrate that all specimens described as L. e. homeyeri in this collection have to be attributed to the nominate subspecies; only the specimen described as L. przelwaskii (now L. e. leucopterus) is a true L. e. homeyeri. According to these data, the ssp. homeyeri must be considered very rare in Italy, contrarily to some previously reported information. Specimens ascribed to L. borealis sibiricus do not show the characters of this subspecies, consequently they should not be included in the check list of Italian species.]&#x0D; [Article in Italian]

Lip mass

A 54-year-old man was referred to an oral surgeon for the evaluation of a mass in his lip. The patient indicated that the lesion had been present “for some time” and was growing slowly. His medical history was only significant for penicillin allergy. No history of trauma to the area was reported. Head and neck examination was noncontributory. Intraoral examination revealed the presence of a nodular lesion in the lower left lip covered by intact mucosa. The mass measured approximately 0.6 centimeters across, was nontender, and displayed a firm consistency (Figure 1). The clinical impression was fibrosed mucocele. An excisional biopsy under local anesthesia was performed, and the specimen was submitted for histologic evaluation. Microscopic examination revealed a well-circumscribed cellular nodule demonstrating sheets and closely packed irregular nests and bands with a vague storiform pattern of oval to polygonal cells with oval to irregularly shaped nuclei and scant cytoplasm with indistinct cytoplasmic borders (Figures 2 and 3). Foamy macrophages and multinucleated cells were noted. Mitotic figures (6 per 10 high-power field), some atypical, were identified. Immunohistochemical studies demonstrated lesional cells to be consistently positive to histiocytic markers (cluster of differentiation [CD]68 and CD163; Figure 4) and CD4 (often expressed in histiodendritic neoplasms). 1 Emile J.F. Abla O. Fraitag S. et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 2016; 127: 2672-2681 Crossref PubMed Scopus (747) Google Scholar ALK-1, lysozyme, dendritic markers (factor XIIIa, CD21), and myoid markers (desmin, smooth muscle actin) were negative. Figure 2Low-powered view showing a circumscribed cellular proliferation arranged in intersecting bundles. The arrows point out the circumscription of the tumor cells (hematoxylin-eosin, original magnification x40). View Large Image Figure Viewer Download Hi-res image Figure 3Medium-powered view showing a proliferation of ovoid to polygonal mesenchymal cells with vague storiform regimentation and an interspersed Touton like multinucleated giant cell (arrow) (hematoxylin-eosin, original magnification x200). View Large Image Figure Viewer Download Hi-res image Figure 4Lesional cells are strongly highlighted by the cluster of differentiation 163 marker (immunostain, original magnification x400). View Large Image Figure Viewer Download Hi-res image Dr. Alshagroud is an assistant professor, Advanced Oral and Maxillofacial Pathology Program, Department of Oral Diagnostic Sciences, School of Dental Medicine, King Saud University, Riyadh, Saudi Arabia. Dr. Alharbi is a senior resident, Advanced Oral and Maxillofacial Pathology Program, Department of Oral Diagnostic Sciences, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY. Dr. Caplash is the acting chair, Dentistry/Oral and Maxillofacial Surgery, Rochester Regional Health System, a member of the attending faculty, University of Rochester, and in private practice, Rochester, NY. Dr. Merzianu is an associate professor, Department of Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, NY. Dr. Aguirre is the program director, Advanced Oral and Maxillofacial Pathology, and a professor, Department of Oral Diagnostic Sciences, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY.

Architecture and Synthesis for Area-Efficient Pipelining of Irregular Loop Nests

Modern high-level synthesis (HLS) tools commonly employ pipelining to achieve efficient loop acceleration by overlapping the execution of successive loop iterations. While existing HLS pipelining techniques obtain good performance with low complexity for regular loop nests, they provide inadequate support for effectively synthesizing irregular loop nests. For loop nests with dynamic-bound inner loops, current pipelining techniques require unrolling of the inner loops, which is either very expensive in resource or even inapplicable due to dynamic loop bounds. To address this major limitation, this paper proposes ElasticFlow, a novel architecture capable of dynamically distributing inner loops to an array of processing units (LPUs) in an area-efficient manner. The proposed LPUs can be either specialized to execute an individual inner loop or shared among multiple inner loops to balance the tradeoff between performance and area. A customized banked memory architecture is proposed to coordinate memory accesses among different LPUs to maximize memory bandwidth without significantly increasing memory footprint. We evaluate ElasticFlow using a variety of real-life applications and demonstrate significant performance improvements over a state-of-the-art commercial HLS tool for Xilinx FPGAs.