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Background Despite its global significance, challenges associated with understanding the epidemiology and accurately detecting, measuring, and characterizing the true burden of seasonal influenza remain in many resource-poor settings. Methods A prospective observational study was conducted in Cambodia at 28 health facilities between 2007 and 2020 utilizing passive surveillance data of patients presenting with acute undifferentiated febrile illness (AUFI) to describe the prevalence of influenza A and B and characterize associated risk factors and symptoms using a questionnaire. A comparison of rapid influenza diagnostic tests (RIDTs) and real-time reverse transcription polymerase chain reaction (rRT-PCR) results was also conducted. Results Of 30 586 total participants, 5634 (18.4%) tested positive for either influenza A or B, with 3557 (11.6%) positive for influenza A and 2288 (7.5%) positive for influenza B during the study. Influenza A and B were strongly associated with the rainy season (odds ratio [OR], 2.30; P <.001) and being from an urban area (OR, 1.45; P <.001). Analysis of individual symptoms identified cough (OR, 2.8; P <.001), chills (OR, 1.4; P <.001), and sore throat (OR, 1.4; P <.001) as having the strongest positive associations with influenza among patients with AUFI. Analysis comparing RIDTs and rRT-PCR calculated the overall sensitivity of rapid tests to be 0.492 (95% CI, 0.479–0.505) and specificity to be 0.993 (95% CI, 0.992–0.994) for both influenza type A and B. Conclusions Findings from this 14-year study include describing the epidemiology of seasonal influenza over a prolonged time period and identifying key risk factors and clinical symptoms associated with infection; we also demonstrate the poor sensitivity of RIDTs in Cambodia. [ABSTRACT FROM AUTHOR]

Diarrheal diseases are a leading cause of mortality and morbidity, disproportionally affecting persons residing in low and middle-income countries. Accessing high-resolution surveillance data to understand community-level etiology and risk remains challenging, particularly in remote and resource limited populations. A multi-year prospective cohort study was conducted in two rural and two peri-urban villages in Cambodia from 2012 to 2018 to describe the epidemiology and etiology of acute diarrheal diseases within the population. Suspected diarrheal episodes among participants were self-reported or detected via routine weekly household visits. Fresh stool and fecal swabs were tested, and acute-illness and follow-up participant questionnaires collected. Of 5027 enrolled participants, 1450 (28.8%) reported at least one diarrheal incident. A total of 4266 individual diarrhea case events were recorded. Diarrhea incidence rate was calculated to be 281.5 persons per 1000 population per year, with an event rate of 664.3 individual diarrhea events occurring per 1000 population per year. Pathogenic Escherichia coli, Aeromonas spp., and Plesiomonas shigelloides were the most prevalent bacterial infections identified. Hookworm and Strongyloides stercoralis were the predominant helminth species, while Blastocystis hominis and Giardia lamblia were the predominant protozoan species found. Norovirus genotype 2 was the predominant virus identified. Mixed infections of two or more pathogens were detected in 36.2% of positive cases. Risk analyses identified unemployed status increased diarrhea risk by 63% (HR = 1.63 [95% CI 1.46, 1.83]). Individuals without access to protected water sources or sanitation facilities were 59% (HR = 1.59 [95% CI 1.49, 1.69]) and 19% (HR = 1.19 [95% CI 1.12, 1.28]) greater risk of contracting diarrhea, respectively. Patient-level surveillance data captured in this long-term study has generated a unique spatiotemporal profile of diarrheal disease in Cambodia. Understanding etiologies, together with associated epidemiological and community-level risk, provides valuable public health insight to support effective planning and delivery of appropriate local population-targeted interventions. [ABSTRACT FROM AUTHOR]

Background: The development of respiratory infections secondary to Aspergillus spp. spores found ubiquitously in the ambient environment is uncommon in immunocompetent patients. Previous reports of invasive upper airway aspergillosis in immunocompetent patients have generally demonstrated the efficacy of treatment regimens utilizing antifungal agents in combination with periodic endoscopic debridement, with symptoms typically resolving within months of initiating therapy.Case Presentation: A 43-year-old previously healthy female presented with worsening respiratory symptoms after failing to respond to long-term antibiotic treatment of bacterial sinusitis. Biopsy of her nasopharynx and trachea revealed extensive fungal infiltration and Aspergillus fumigatus was isolated on tissue culture. Several months of oral voriconazole monotherapy failed to resolve her symptoms and she underwent mechanical debridement for symptom control. Following transient improvement, her symptoms subsequently returned and failed to fully resolve in spite of increased voriconazole dosing and multiple additional tissue debridements over the course of many years.Conclusions: Invasive upper airway aspergillosis is exceedingly uncommon in immunocompetent patients. In the rare instances that such infections do occur, combinatorial voriconazole and endoscopic debridement is typically an efficacious treatment approach. However, some patients may continue to experience refractory symptoms. In such cases, continued aggressive treatment may potentially slow disease progression even if complete disease resolution cannot be achieved. [ABSTRACT FROM AUTHOR]

Objectives: Limited literature is available on the tumor microenvironment (TM) of upper tract urothelial carcinoma (UTUC). This study comprehensively reviews programmed death 1 receptor (PD-1)-positive and CD8+ tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression on tumor epithelium (TE).Methods: Seventy-two nephroureterectomy specimens were analyzed for PD-L1, PD-1, and CD8. One percent or more tumor and lymphohistiocyte PD-L1 expression was considered positive. TIL density by H&E was scored semiquantitatively from 0 to 3, and CD8+ and PD-1+ TILs were quantified in hotspots.Results: Of the cases, 37.5% demonstrated PD-L1+ on TE. PD-L1+ TE showed an association with pathologic stage (P = .01), squamous differentiation (SqD) (P < .001), TILs by H&E (P = .02), PD-1+ peritumoral TILs (P = .01), and PD-L1+ peritumoral lymphohistiocytes (P = .002). Finally, there was a significant difference in PD-1+ peritumoral TILs in cases with SqD vs no SqD (P = .03).Conclusions: Aggressive UTUC is associated with a distinct TM. Furthermore, TM of UTUC-SqD was distinctly different from those with no SqD, warranting study in a larger cohort. [ABSTRACT FROM AUTHOR]

Sclerosing rhabdomyosarcoma (RMS) is a rare subtype of RMS with unique prominent stromal hyalinization and a pseudovascular architecture. It overlaps morphologically with spindle cell RMS and poses both diagnostic and therapeutic challenges because of its rarity and aggressive clinical course. In this article, we report a case of sclerosing RMS arising from a prior craniotomy site, which demonstrated both sclerosing and spindle cell components. A literature review of RMS with sclerosing morphology identified 122 cases. Our review documents the following: sclerosing RMS occurs in both childhood and adult populations, has a predilection for the head and neck areas, and has a worse prognosis in adults. Sclerosing RMS harbors a high frequency of MYOD1 mutations, conferring a poor clinical outcome. Sclerosing RMS and spindle RMS likely represent a morphologic spectrum of one entity. [ABSTRACT FROM AUTHOR]

Abstract: Background: Leiomyosarcoma is a rare neoplasm of the head and neck. The purpose of this study was to present our single‐institution case series of head and neck leiomyosarcoma and a review of cases in the National Cancer Data Base (NCDB). Methods: Patients with head and neck leiomyosarcoma at the University of Pennsylvania and in the NCDB were identified. Demographic characteristics, tumor factors, treatment paradigms, and outcomes were evaluated for prognostic significance. Results: Nine patients with head and neck leiomyosarcoma from the institution were identified; a majority had high‐grade disease and cutaneous leiomyosarcoma, with a 5‐year survival rate of 50%. Two hundred fifty‐nine patients with leiomyosarcoma were found in the NCDB; macroscopic positive margins and high‐grade disease were associated with poor prognosis (P < .01), and positive surgical margins were related to adjuvant radiation (P < .001). Conclusion: Head and neck leiomyosarcoma presents at a high grade and is preferentially treated with surgery. Several demographic and tumor‐specific factors are associated with outcomes and prognosis. [ABSTRACT FROM AUTHOR]

The article presents case studies of two patients with unusual morphologic and immunophenotypic changes observed in a giant-cell tumor (GCT) of bone after treating with denosumab (AMG 162). It discusses the application of positron emission tomography (PET)/computed tomography (CT). Information about denosumab, a monoclonal antibody, is provided.

PEComas are mesenchymal neoplasms composed of perivascular epithelioid cells (PEC) and include a spectrum of tumors. PEComas and malignant melanoma share common morphological, immunohistochemical, and ultrastructural features, such as epithelioid cell morphology and melanocytic immunophenotype. Melanocytic markers commonly expressed in PEC tumors include HMB-45, Melan-A/MART-1, tyrosinase, microphthalmia transcription factor (MITF), and occasionally, S100. Given this morphological and immunophenotypical overlap, the differential diagnosis between a PEComa and malignant melanoma can represent a challenge. Additional diagnostic difficulty is the differentiation of melanoma and PEComa from clear cell sarcoma that is indistinguishable from melanoma based on the immunohistochemical profile. Recent studies have shown that MUM-1, a known lymphocyte marker shows positive immunostaining in nevi and melanomas, its expression in PEComas and clear cell sarcoma, however, has not been previously addressed. In this study, the authors analyzed MUM-1 expression using immunohistochemistry in PEComas (n = 8), the PEComa family members, angiomyolipomas (n = 13), and clear cell sarcomas (n = 11) and compared the staining pattern with malignant melanomas (n = 25), both primary (n = 14) and metastatic (n = 11). It was found that 92.3% of primary melanomas and 81.3% of metastatic melanomas were MUM-1 positive. In contrast, MUM-1 was only weakly positive in only 25% of PEComas and negative in all angiomyolipomas. MUM-1 expression was noted in 72.7% of clear cell sarcomas. The study demonstrated differential MUM-1 expression between PEComas and other true melanocytic tumors and suggested that the addition of MUM-1 to the usual panel of melanocyte markers could be a helpful adjunctive study to aid in the differential diagnosis between these entities. [ABSTRACT FROM PUBLISHER]

We report an unusual, rare case of primary epithelioid rhabdomyosarcoma of a lymph node in the parotid basin. A 72-year-old man with a history of squamous cell carcinoma of the forehead and cheek had a 5-cm mobile nontender mass of the parotid tail and right level II region. A positron emission tomography/computed tomography scan confirmed a hypermetabolic soft tissue mass in the right parotid gland. Histologic sections showed an intraparotid lymph node almost completely effaced by a centrally necrotic malignant epithelioid neoplasm consisting of uniform-appearing dyshesive cells exhibiting rhabdoid morphologic features with abundant eosinophilic fibrillary cytoplasm, eccentric nuclei, and prominent nucleoli. Bizarre cells were not seen. In immunohistochemical studies, neoplastic cells expressed desmin and myogenin. Electron microscopy showed a mixture of thick and thin filaments, primitive Z-band formation, and well-formed sarcomeres. Fluorescence in situ hybridization studies for FOXO1, PAX3, and/or PAX7 rearrangements were negative. An extensive clinical and radiologic workup showed no evidence of primary tumor elsewhere. Complete resection of the tumor was performed, and adjuvant chemotherapy was given; patient was disease free 12 months after surgery. [ABSTRACT FROM AUTHOR]

The DNA-binding factor TFE3 is closely related to microphthalmia-associated transcription factor (MiTF) and is over-expressed in alveolar soft part sarcoma (ASPS) and select renal cell carcinomas. Reports of TFE3 expression in PEComa prompted investigation into TFE3 expression among other members of the putative MiTF group of neoplasms. The authors examined cases of PEComa (n = 6), conventional angiomyolipoma (AML; n = 22), metastatic melanoma (n = 16), and clear cell sarcoma (CCS; n = 9) for TFE3 expression. Nuclear immunostaining was observed in 74% (39/53) of cases, as follows: 5/6 PEComas, 18/22 AMLs, 10/16 metastatic melanomas, and 6/9 CCSs. However, with the exception of PEComas, compared with ASPS controls, TFE3 staining was significantly less intense in the tumors examined. These results illustrate that TFE3 immunoreactivity is detectable in other members of the MiTF family of neoplasms. For this reason, such neoplasms warrant consideration in the differential diagnosis with nuclear TFE3 immunoreactivity, particularly when staining is focal and less intense. [ABSTRACT FROM PUBLISHER]

Background: A hemosiderotic fibrohistiocytic lipomatous lesion, also called hemosiderotic fibrolipomatous tumor, is a rare and recently described fibrolipomatous entity. Initially considered the result of a reactive inflammatory process from trauma or vascular disease, newer evidence suggests it may be neoplastic in origin. Case report: We report the case of a 56-year-old woman with a painful mass in the dorsal aspect of the foot diagnosed as a hemosiderotic fibrohistiocytic lipomatous lesion. Literature review: We reviewed all 31 published cases of hemosiderotic fibrohistiocytic lipomatous lesions looking for common clinical, imaging, and histologic patterns. Hemosiderotic fibrohistiocytic lipomatous lesions occur predominantly in the fifth and sixth decades of life (average age, 49.5 years; range, 0.67–74 years). Females predominate 22 to 9. Thirteen of 28 patients had histories of trauma or vasculopathy. Twenty-six of 31 lesions were in the foot. The MRI signal of a hemosiderotic fibrohistiocytic lipomatous lesion follows fat in all sequences. Stranding or septations also frequently are seen. Histologically, the lesions are composed of three main elements in varying proportions: mature adipocytes, spindle cells, and hemosiderin pigment. Ten of 27 resected lesions recurred. Resection types are not reported in many cases. Four of 15 lesions recurred after marginal/intralesional excision, whereas none of three lesions treated by wide excision recurred. Purpose and clinical relevance: The high recurrence rate may be related to the difficulty in determining intraoperatively that a resection is complete, secondary to the lack of anatomic boundaries such as a pseudocapsule. Any attempt at wide resection must weigh the morbidity of this surgery against that of a recurrence after a resection which seemed complete intraoperatively. There have been no reports of metastasis. [ABSTRACT FROM AUTHOR]

The article presents a case report for a 53 year old man with a history of melanoma who presented to orthopedic surgeons with complaints of pain in his right forearm. A discussion of medical tests which were performed on the patient and resulted in him receiving a diagnosis of osteosarcoma of the proximal part of the radius and Mazabraud syndrome is presented. The patient's medical care and recovery are discussed.

We describe a case of a venous hemangioma that arose in the optic nerve sheath of the orbital apex in a 28-year-old man who presented with progressive vision loss. To the best of our knowledge, this is the first reported case of a venous hemangioma occurring at this location. A definitive diagnosis and partial excision was achieved via an endoscopic transsphenoethmoid approach with interactive, computer-assisted, frameless stereotactic surgical navigation. The intervention resulted in minimal morbidity, demonstrating yet again that this surgical approach is a safe and effective way to treat lesions of the orbital apex. [ABSTRACT FROM AUTHOR]

The vast majority of soft tissue tumors (STT), especially sarcomas, should be examined according to a national standard for pathologic evaluation, including a national consensus on a grading system and elements of a synoptic pathology report. The margins should be separated into fascial margins and other surgically cut margins. If questions about the diagnosis arise, a second opinion should be sought from an expert in sarcoma pathology. Whenever possible, tissue should be frozen for potential molecular diagnosis and additional tissue banked for research. Finally, there is a need for a national registry for rare sarcoma types. [ABSTRACT FROM AUTHOR]

The prognostic importance of HER-2 status in breast cancer has been investigated extensively, but findings have not been uniform across immunohistochemical studies using fixed, paraffin-embedded specimens. We speculate that studies with an overrepresentation of large tumors might not produce evidence for an independent effect of a single marker because breast tumors of larger size tend to exhibit multiple adverse attributes as the malignancy advances through the metastatic cascade. Further, it has been posited that results from certain studies of biologic markers might be generalizable only to larger tumors because tumor repositories tend to house a disproportionate number of larger tumors. To test our hypothesis that the prognostic effect of HER-2 status might be modified by the size of the tumor, we conducted a survival analysis of a nested case-case sample of 156 women diagnosed with primary breast cancer from 1983 to 1995. Relative risks (RRs) and confidence intervals (CIs) for recurrence in relation to HER-2 status were estimated using a multivariate Cox proportional hazards model. Immunohistochemistry of archival tissue was used to detect HER-2 expression. Positive HER-2 status was associated with recurrence (RR = 4.24, 95% CI 1.30–13.78) among patients with axillary lymph node-positive involvement. This analysis identified an interaction (p < 0.01) between tumor size and overexpression. Stratification by tumor size revealed an increased risk of recurrence associated with HER-2-positive tumors that were ≤2 cm in size (RR = 13.68, 95% CI 1.06–175.76), whereas no such association was observed among patients with HER-2-positive tumors larger than 2 cm. Eligible patients without available tumor tissue tended to have smaller tumors compared to study participants. Our results might partly explain the variation in evidence across HER-2 prognostic studies using fixed tissue and might apply to other putative markers of prognosis in breast cancer. [ABSTRACT FROM AUTHOR]

Background: Because cells progressing to cancer must proliferate, marker proteins specific to proliferating cells may permit detection of premalignant lesions. Here we compared the sensitivities of a classic proliferation marker, Ki-67, with a new proliferation marker, MCM2, in 41 bronchial biopsy specimens representing normal mucosa, metaplasia, dysplasia, and carcinoma in situ. Methods: Parallel sections were stained with antibodies against MCM2 and Ki-67, and the frequencies of staining were independently measured by two investigators. Differences were evaluated statistically using the two-sided correlated samples t-test and Wilcoxon rank sum test. Results: For each of the 41 specimens, the average frequency of staining by anti-MCM2 (39%) was significantly (p < 0.001) greater than by anti-Ki-67 (16%). In metaplastic lesions anti-MCM2 frequently detected cells near the epithelial surface, while anti-Ki-67 did not. Conclusions: We conclude that MCM2 is detectable in 2-3 times more proliferating premalignant lung cells than is Ki-67. The promise of MCM2 as a sensitive marker for premalignant lung cells is enhanced by the fact that it is present in cells at the surface of metaplastic lung lesions, which are more likely to be exfoliated into sputum. Future studies will determine if use of anti-MCM2 makes possible sufficiently early detection to significantly enhance lung cancer survival rates. [ABSTRACT FROM AUTHOR]

Primary sarcomas of the salivary gland region occur rarely and may be confused with other primary salivary gland neoplasms. This distinction is critical, as the treatment of salivary gland sarcomas differs significantly from the therapy of the more common tumors typically found in these glands. We report an unusual case of synovial sarcoma arising within the parotid gland of a 51-year-old female. Large areas were monophasic and resembled hemangiopericytoma, but a focal unequivocal biphasic area was noted. Previous cases reported in this region are reviewed. [ABSTRACT FROM AUTHOR]

Most low-grade endometrial stromal sarcomas are intrauterine in origin, and a primary extrauterine location in the mesentery or omentum is extraordinarily rare. Hence, we report a well-documented, low-grade endometrial stromal sarcoma of extrauterine origin as an incidental finding in a patient who had extensive ovarian intra-abdominal carcinomatosis. This case adds to the literature experience in this entity and illustrates that such lesions may occur as incidental and unexpected findings in patients with other gynecologic neoplasms. [ABSTRACT FROM AUTHOR]

Total RNA was extracted from five malignant fibrous histiocytomas and two benign fibrohistiocytic lesions and assayed for mRNA expressions for transforming growth factor beta (TGF-β) and c-sis by Northern blot analysis. Production of both of these has been associated with cells of monocyte-macrophage lineage, and these factors have been shown to be important in physiologic mesenchymal cell proliferation. No mRNA expression of either TGF-β or c-sis was identified in any of the fibrohistiocytic tumor samples. The lack of expression of TGF-β and c-sis may be consistent with a nonhistiocytic origin of malignant fibrous histiocytoma, or may reflect transformation-associated loss of the normal molecular mechanisms of mesenchymal proliferation. The absence of c-sis mRNA expression can be reconciled with the prior immunohistochemical demonstration of platelet-derived growth factor in tumor cells of malignant fibrous histiocytoma. [ABSTRACT FROM AUTHOR]

Examines the gas sensing mechanism of iron phthalocyanine by transmission Mossbauer spectroscopy and conversion electron Mossbauer spectroscopy. Surface interactions; Effect of ambient temperatures and pressures.

Ossifying fibromyxoid tumors are rare soft-tissue neoplasms, usually with an indolent course. However, atypical/malignant variants have been described, showing either local recurrence after complete excision or metastasis to the lungs, mediastinum, adrenals, or soft tissue. We report the case of an ossifying fibromyxoid tumor of the left ankle that metastasized to the lung and thyroid gland 12 years after the initial diagnosis and surgical treatment. To our knowledge, this is the first reported case of this neoplasm metastasizing to the thyroid gland. [ABSTRACT FROM AUTHOR]

Angiomatosis is a rare benign lesion of the head and neck that can be mistaken for either a vascular malformation or malignant disease as a result of its infiltrative nature. The recurrence rate of angiomatosis requiring surgery is reported to be >90%, and as such the otolaryngologist treating this condition should endeavor to remove all disease during the first operation while maintaining a high level of suspicion for recurrence during postoperative surveillance. This case represents the first report of angiomatosis involving the nose and/or paranasal sinuses, and extends the differential diagnosis of sinonasal tumors, of which the otolaryngologist must be aware. A description of the surgical care and postoperative surveillance recommendations is detailed in this first reported case of angiomatosis of the paranasal sinuses. [ABSTRACT FROM AUTHOR]

A dermoid cyst is an ectodermally differentiated form of teratoma. Its occurrence in the parotid gland is very rare. Such a presentation must be properly evaluated in order to rule out malignancy. We describe the diagnostic evaluation and surgical management of a parotid dermoid cyst in an 18-year-old man. We also review the embryologic pathogenesis of the tumor and the usefulness of the physical examination, preoperative fine-needle aspiration cytology, magnetic resonance imaging, and computed tomography in evaluating the extent of the tumor, its histologic features, and its cystic characteristics. Finally, we discuss the role of surgical management in terms of preserving facial nerve integrity and preventing recurrence. [ABSTRACT FROM AUTHOR]

An abstract of the article "Utility of Fine-Needle Aspiration in the Diagnosis of Lymphomas Mimicking Primary Bone and Soft Tissue Sarcomas," by Michiko Nagamine, Julieta E. Barroeta, Eugene D. Smith, Christian M. Ogilvie, Richard D. Lackman and John S. Brooks is presented.

A letter to the editor is presented about the classification of tumors.

The article presents information on the "International Journal of Surgical Pathology." The reasons why the perception that there are already too many journals soliciting too few manuscripts in the field may not be completely accurate are cited. There has been an increase in the total number of abstracts received by the U.S.-Canadian Division of the International Academy of Pathology. An explanation for this unambiguous rise is provided.

Presents updates on markers in soft tissue tumors from the International Society of Bone and Soft Tissue Pathologists for 2004. Characteristics of the D240 marker; Application of nuclear transcription factors to soft tissue tumors; Frequency of CD10 reactivity in selected soft tissue tumors.