Level of Agreement With a Multi-Test Approach to the Diagnosis of Diabetic Foot Osteomyelitis.

Although bone biopsy has historically been considered the "gold standard" or "standard reference" for the diagnosis of diabetic foot osteomyelitis, some contemporary investigations have provided evidence against this as a single diagnostic test and in support of a combination of clinical, laboratory, and radiographic findings. The objective of this investigation was to measure the level of agreement between several commonly used forms of diagnostic testing for diabetic foot osteomyelitis. A retrospective chart review was performed of 50 consecutive patients admitted to a single tertiary healthcare center with the documented performance of 1) a clinical probe-to-bone test on hospital admission; 2) plain film radiographs prior to any surgical intervention; 3) magnetic resonance imaging prior to any surgical intervention; and an intraoperative excisional bone debridement performed, with samples sent for both 4) histologic analysis and 5) microbiologic analysis. A frequency count of agreement among these 5 tests was performed, and the interobserver (or inter-test) agreement was measured using the kappa statistic. We observed low levels of inter-test agreement between the 5 diagnostic tests (range 42.0%-62.0%), and levels of chance-corrected agreement were well below what would be considered appropriate for a "gold standard" or "standard reference." Levels of the kappa statistic ranged from 0.0 to 0.220, with most inter-test comparisons falling in the "poor agreement" and "slight agreement" interpretation ranges. The highest level of agreement occurred between the plain film radiographs and magnetic resonance imaging (62.0% agreement and kappa statistic of 0.220). Although it is likely that a combination of clinical, radiographic, and laboratory tests provides the best diagnostic approach for diabetic foot osteomyelitis, the data provided herein indicate that the tests themselves might have high intrinsic levels of unreliability and that the specific combination of tests that might be best used remains unclear.

Creation of rabbit bone and soft tissue tumor using cultured VX2 cells.

BACKGROUND: To create rabbit VX2 bone tumors, it is surgically less demanding to implant VX2 cell suspensions than minced tumor fragments. A VX2 cell line that can be expanded using standard cell culture techniques might provide an unlimited supply of cells needed to create these bone tumors. Therefore, the aim of the present study was to establish a VX2 cell line and verify its tumorigenicity in an athymic mouse and rabbit animal model. MATERIALS AND METHODS: Minced VX2 tumor fragments were allowed to grow as a monolayer in 10 mL Dulbecco's modified Eagle medium/nutrient mixture F-12 (1:1) supplemented with 10% fetal calf serum and passaged multiple times. The tumorigenecity of the cultured VX2 cells were tested in athymic mice (intradermal tumor development) and in New Zealand white rabbits (bone and soft tissue tumor model). RESULTS: The VX2 cells proliferated rapidly in tissue culture flasks containing Dulbecco's modified Eagle medium/nutrient mixture F-12 medium supplemented with 10% fetal bovine serum. After reaching confluence, the VX2 cells can only be subcultured when plated at a greater density (e.g., at a dilution of 1:1). All 6 athymic mice developed tumors within 15 d of VX2 cell suspension implantation. In the rabbits, the VX2 cells were able to produce tumors in muscle tissue and in the distal femurs but not in the proximal tibia. CONCLUSIONS: VX2 cell lines can be successfully created from VX2 tumor fragments and passaged multiple times. In contrast to previous reports, the VX2 cells grown in vitro are capable of maintaining their tumorigenecity. However, successful tumor growth might depend on the initial number of cells implanted and the use of extracellular matrices for tumor proliferation.

Primary amyloidosis involving mesenteric lymph nodes: diagnosis by fine-needle aspiration cytology.

BACKGROUND: Mesenteric lymph node amyloid deposits are rare and may be seen in isolated or secondary amyloidosis. The diagnosis of mesenteric amyloidosis has conventionally relied on histopathological examination following an exploratory laparotomy or a biopsy. CASE: A 72-year-old male previously diagnosed with Waldenström's macroglobulinemia and multiple other malignancies was admitted for abdominal pain. An abdominal computed tomography (CT) scan revealed diffuse retroperitoneal and mesenteric lymphadenopathy associated with bowel wall thickening. A CT-guided fine-needle aspiration (FNA) cytology and core biopsies of mesenteric lymph nodes were performed. The FNA smears revealed irregular, waxy, basophilic clumps on a Diff-Quik stain and cyanophilic clumps of amorphous material on a Papanicolaou stain. The lymph node aspirates showed positivity for the Congo red stain, confirming it as amyloid. In situ hybridization studies revealed a predominance of λ light chains, and a diagnosis of primary amyloidosis involving mesenteric lymph nodes was made. Supplemental needle core biopsies showed positivity for Congo red and Crystal violet stains and exhibited the classic apple-green birefringence under polarized light. CONCLUSION: The involvement of lymph nodes in amyloidosis is not uncommon; however, the involvement of mesenteric lymph nodes in a setting of macroglobulinemia and its diagnosis by FNA cytology is novel to this case.

Statistical reliability of bone biopsy for the diagnosis of diabetic foot osteomyelitis.

Bone biopsy is often referred to as the reference standard for the diagnosis of diabetic foot osteomyelitis (OM), and it also serves as an important interventional tool with respect to diabetic foot infections and limb salvage. However, the phrase bone biopsy lacks a standardized definition, and the statistical reliability of the pathologic diagnosis has not been previously examined. The objective of the present study was to quantify the reliability of the histopathologic analysis of bone with respect to the diagnosis of diabetic foot OM. Four pathologists, kept unaware of the previous pathology reports and specific patient clinical characteristics, retrospectively reviewed 39 consecutive tissue specimens and were informed only that it was "a specimen of bone taken from a diabetic foot to evaluate for OM." As a primary outcome measure, the pathologists were asked to make 1 of 3 possible diagnoses: (1) no evidence of OM, (2) no definitive findings of OM, but cannot rule it out, or (3) findings consistent with OM. There was complete agreement among all 4 pathologists with respect to the primary diagnosis in 13 (33.33%) of the 39 specimens, with a corresponding kappa coefficient of 0.31. A situation of clinically significant disagreement, or in which at least 1 pathologist diagnosed "no evidence of OM," but at least 1 other pathologist diagnosed "findings consistent with OM," occurred in 16 (41.03%) of the specimens. These results indicate agreement below the level of a "reference standard" and emphasize the need for a more comprehensive diagnostic protocol for diabetic foot OM.

The Association of Invasive Cribriform Lesions With Adverse Prostatic Adenocarcinoma Outcomes: An Institutional Experience, Systematic Review, and Meta-analysis.

CONTEXT.­: Recent studies and a few reviews suggest that presence of invasive cribriform lesions (ICLs) in prostatic acinar adenocarcinoma correlates with adverse outcomes. However, a systematic review with meta-analysis on this correlation is currently lacking. OBJECTIVE.­: To compare the likelihood of adverse outcomes by the status of ICLs in prostatic acinar adenocarcinoma with the meta-analysis of high-quality published data and institutional experience. DATA SOURCES.­: PubMed, Scopus, manually searched references, and institutional data. STUDY SELECTION.­: Observational retrospective case-control studies or prospective cohort studies of adverse outcomes stratified by the status of ICLs were selected. DATA EXTRACTION.­: Study quality was analyzed. The prevalence of adverse outcomes stratified by the status of ICLs was extracted. CONCLUSIONS.­: Eighty-five cases were reviewed. Extraprostatic extension, seminal vesicle invasion, and regional lymph node metastasis were observed in 18 (45%), 14 (35%), and 7 (17.5%) of the 40 cases with cribriform lesions, respectively. These features were observed in 4 (8.9%), 1 (2.2%), and 0 (0%) of the 45 cases without ICLs. During the follow-up, biochemical prostate-specific antigen recurrence, local recurrence, and metastasis/disease-specific death were documented in 7 (17.5%), 2 (5%), and 2 (5%) of the 40 cases with ICLs. These poor outcomes were found in 6 (13.3%), 1 (2.2%), and 1 (2.2%) of the 45 cases without ICLs. Meta-analysis revealed a significant increase in the risk of adverse outcomes in patients who had ICLs relative to those who did not (odds ratio, 3.95; 95% CI, 2.61-5.97; I2 = 53%; Z = 6.52; P < .01). These results suggest that presence of ICLs is associated with adverse outcomes.

Moving Toward a Systematic Approach for Reporting Salivary Gland Cytopathology: An Institutional Experience and Literature Review.

CONTEXT.­: Despite the clinical utility of fine-needle aspiration for the diagnosis of salivary pathologies, salivary lesions remain one of the most challenging areas in cytopathology. This is partially because there is no consensus on how to report salivary gland cytopathology, which has resulted in inconsistent terminology among institutions and individual cytopathologists and in confusion in communication among cytopathologists and ordering providers. OBJECTIVE.­: To summarize our experience with an institutional salivary gland cytopathology reporting system, as an initiative to promote collaborative work toward a consensus on a reporting system. DESIGN.­: We developed an empirical 6-tier classification reporting system. Slides of 107 salivary gland fine-needle aspirations with subsequent histology slides were reviewed and reclassified using the 6-tier system. The performance of the cytology reporting system was evaluated with the histology diagnoses serving as the gold standard. RESULTS.­: Fine-needle aspiration diagnoses made based on the institutional 6-tier classification system were generally consistent with histology diagnoses for the disease spectrum reported in this study. The sensitivity, specificity, positive predictive value, and negative predictive value for diagnosing malignancies with the system were 86% (12 of 14), 93% (40 of 43), 80% (12 of 15), and 95% (40 of 42), respectively. The risk of malignancy increased from 0% (0 of 13) for negative for neoplasm to 7% (2 of 29) for benign neoplasm, 67% (2 of 3) for suspicious for malignancy, and 83% (10 of 12) for positive for malignancy. CONCLUSIONS.­: The institutional 6-tier system provides a succinct, risk-of-malignancy-based system to report salivary gland cytology. Our experience with this system helps to pave the way for the adoption of the Milan System for Reporting Salivary Gland Cytopathology.

High prevalence of discordant human papillomavirus and p16 oropharyngeal squamous cell carcinomas in an African American cohort.

BACKGROUND: Most studies on human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC) have been performed on white Americans. Our study examined the incidence of HPV in an African American oropharyngeal SCC cohort and its survival. METHODS: African American patients with oropharyngeal SCC in a combined tumor registry were identified. HPV16 testing was performed by polymerase chain reaction (PCR) from DNA extracted from tumor blocks. The p16 staining was performed using standard immunohistochemistry. RESULTS: Forty-four patients were identified for analysis. Seventy-three percent of the tumors were HPV-positive. Only 39% of the patients who were HPV-positive were also p16-positive. Survival between all 3 tumor types, patients who tested HPV-positive/p16, HPV-positive/p16-positive, and HPV-negative/p16-negative was significantly different (p = .03). HPV/p16 status was significant on univariate and multivariate analysis. CONCLUSION: HPV oropharyngeal SCC is strongly present in this African American cohort. Two thirds of the patients who were HPV-positive were p16-negative. Greater study is needed to explain the high p16 negativity among this HPV-positive oropharyngeal SCC African American cohort. © 2015 Wiley Periodicals, Inc. Head Neck 38: E867-E872, 2016.

Case report: glomus tumor of the colon.

Glomus tumors are tumors of pericytic origin and are usually found in the distal extremities. Glomus tumors have rarely been reported in viscera. The authors report a glomus tumor of the colon that caused rectal bleeding in a 40-yr-old man and was biopsied and excised endoscopically. The histology and immunohistochemical profile of the tumor are described and the literature on visceral glomus tumors is reviewed.

Fine-Needle Aspiration Biopsy of Salivary Gland Lesions.

CONTEXT: Fine-needle aspiration (FNA) is a well-established diagnostic approach for salivary gland lesions; however, lack of a standard system of terminology for classification of salivary gland neoplasms collected by FNA and the relatively high frequency of uncertainty of diagnosis are likely partly responsible for current confusion in the interpretation of these FNA samples. OBJECTIVE: To propose a novel classification system for reporting salivary gland FNA samples and summarize recent progress in application of molecular and immunohistochemical markers in selected salivary gland neoplasms. DATA SOURCES: Literature review and authors' personal practice experience. CONCLUSIONS: The new classification system provides a more succinct, standardized interpretation of results and will ultimately assist in communication between clinicians, clinical decision making, and preoperative patient counseling. Impressive advances have been made in recent years in the understanding of molecular pathogenesis of salivary gland tumors. With the newly acquired diagnostic tools, significant improvement in diagnostic accuracy of salivary gland FNA can certainly be expected.

Oncocytic Adrenocortical Neoplasm Diagnosed after Robot-Assisted Adrenalectomy.

Oncocytic tumors, composed of eosinophilic, mitochondria-rich cells, can occur in several locations throughout the body. These tumors can occur in the adrenal cortex and are rarely malignant. We report a case of a patient presenting with an incidental adrenal mass which was later diagnosed as a oncocytic adrenocortical neoplasm (OAN). The patient is a 53-year-old man found to have a 7.2 cm right adrenal mass, incidentally found by computed tomography (CT). After metabolic workup was negative, a right robotic adrenalectomy (RA) was performed. Pathologic analysis revealed clusters of large cells with abundant eosinophilic and granular cytoplasm, consistent with OAN. This pathology is rare, with only about 150 cases described in the literature. It occurs in females 2.5 times more frequently and more commonly on the left side. Diagnosis is usually made by imaging criteria, typically with CT or magnetic resonance imaging (MRI). Treatment is generally surgical, since OAN can be malignant in some cases. Differentiation between benign and malignant OAN is done based on the Lin-Weiss-Bisceglia criteria and can be difficult. If malignancy is diagnosed, recurrence is common and close surveillance should be performed.

Detection and diagnostic utilization of placental alkaline phosphatase in muscular tissue and tumors with myogenic differentiation.

Placental alkaline phosphatase (PLAP) is normally produced by primordial germ cells and syncytiotrophoblasts, and the detection of its expression has been useful in the diagnosis of germ cell tumors. We have recently observed PLAP immunoreactivity in normal human adult and fetal muscle tissue. Based on this observation, we explored the possible role of PLAP in the diagnosis of soft tissue tumors. A total of 271 tumors were studied. These included tumors with myogenic, neural, fibrous, myofibroblastic, lipomatous, neuroepithelial, perivascular, and epithelial differentiation. A formalin-fixed, paraffin-embedded section from each tumor was stained with PLAP monoclonal antibody using standard immunohistochemical methods preceded by antigen retrieval. In addition, western blotting with PLAP monoclonal antibodies was performed on fresh samples from a uterine leiomyoma, grossly normal myometrium, and placenta. Also, formalin-fixed sections of fetal skeletal muscle were labeled with double immunohistochemistry techniques using antibodies to myogenin and PLAP. Cytoplasmic PLAP reactivity was detected in all leiomyomas and rhabdomyosarcomas (100%), 7 of 15 (46%) leiomyosarcomas, 15 of 19 (79%) desmoplastic small round cell tumors, 2 of 15 (13%) gastrointestinal stromal tumors, 1 of 8 (13%) Wilms' tumors, 1 of 9 synovial sarcomas (9%), and 2 of 7 (29%) myofibroblastic tumors. No PLAP reactivity was detected in hyperplastic scars, nodular fasciitis, or the other remaining soft tissue and epithelial tumors. Double immunohistochemistry studies showed coexpression of myogenin and PLAP in fetal skeletal muscle cells, and western blot analysis showed a 70-kDa band in samples derived from grossly normal placenta, benign myometrium, and a uterine leiomyoma. PLAP immunoreactivity is detected in soft tissue tumors with known myogenic differentiation. PLAP immunoreactivity seems to relate to the degree of myogenic differentiation in soft tissue tumors and is more frequently expressed in cells with skeletal muscle differentiation and least in those with myofibroblastic features. The biologic function of PLAP in muscle and tumors with myogenic differentiation is unknown and merits further investigation. In addition to its role as a germ cell marker, PLAP may also be used as a myogenic marker in the diagnosis of soft tissue tumors.

Fibrillin and other matrix proteins in mitral valve prolapse syndrome.

BACKGROUND: Unlike myxomatous degeneration in Marfan syndrome, which has been reported to result from a mutation in the gene that codes for the extracellular structural protein fibrillin, no specific molecular abnormality has been documented to be the underlying cause of myxomatous degeneration in mitral valve prolapse syndrome (MVPS). The present study examined the distribution of fibrillin and other extracellular matrix proteins in patients with isolated MVPS. METHODS: Mitral valve leaflets from 7 MVPS patients and 5 rheumatic heart disease (RHD) patients were characterized immunohistochemically for fibrillin, elastin, collagen I, and collagen III distribution, and compared with five normal mitral valves. RESULTS: In normal mitral valve leaflets immunostaining for fibrillin, elastin, collagen I, and collagen III revealed a fibrillary and laminar pattern in the atrialis and the spongiosa. In addition, both the collagens were present in the ventricularis, and the coarse bundles in the fibrosa exhibited alternating bandlike collagen I immunoreactivity. The staining patterns of fibrillin, elastin, and collagens I and III revealed distinctly different distribution in MVPS relative to the normal and RHD leaflets. MVPS leaflets in areas of myxoid degeneration displayed a more diffuse, weaker, and nonlaminar pattern of staining for fibrillin. Similar, but less severe abnormality of elastin, collagen I, and collagen III was also observed. Unlike diffuse abnormality in MVPS, the disruption of extracellular proteins in RHD only occurred at the site of the inflammatory damage, but the overall architecture was preserved. CONCLUSIONS: The results of the current study suggest a primary role for abnormal fibrillin and other matrix proteins in producing myxoid degeneration of mitral valve leaflets in MVPS.

Extraskeletal osteosarcoma: a case report and review of the literature.

We report an instructive case of extraskeletal osteosarcoma in a 63-year-old African American male who presented after an episode of recent trauma, with clinical and radiological features characteristic of this neoplasm. Osteosarcoma is the most common primary malignant tumor of bone in young adults, but the extraskeletal variety is very uncommon. The radiological and pathological features of this neoplasm will be discussed, along with a review of the literature.

Prostate cancer metastatic to the larynx: a case report.

Prostate cancer, which is the most common cancer among men, rarely metastasizes to the neck. We report a case of prostatic carcinoma that metastasized to the larynx in a 71-year-old man who presented with hoarseness and shortness of breath. Computed tomography (CT) detected a 2.9 × 3.1 × 2.6-cm mass that extended from the cricoid and arytenoid cartilages into the superior trachea. Findings on histopathology and immunohistochemistry of the laryngeal tumor were consistent with a metastasis of the patient's earlier prostate cancer. CT of the chest later detected a soft-tissue mass in the right paraspinal area and other thoracic pathology that represented metastatic disease. The patient was treated with palliative radiation therapy. As androgen deprivation therapy continues to increase the life expectancy of prostate cancer patients, detection of distant metastases will likely increase, as well. Urogenital cancer metastatic to the head and neck should be considered in the differential diagnosis of laryngeal masses.

Clear cell sarcoma: a case report with radiological and pathological features of an atypical case.

Clear cell sarcoma of soft tissue is a rare, aggressive soft tissue tumor, which is morphologically similar to malignant melanoma but has no precursor skin lesion and, instead, has a characteristic chromosomal translocation. It is critical, yet challenging, to recognize clear cell sarcoma of soft tissue because the outcome is very different to that of metastatic melanoma. We report a case of clear cell sarcoma of soft tissue arising in the left foot of a 35-year-old African-American woman.

Effect of atorvastatin on the cortical bones of corticosteroid treated rabbits.

Osteoporosis ("secondary" osteoporosis) and avascular necrosis (AVN) of the femoral head are well-known adverse effects of corticosteroid therapy. Statins have been reputed to increase bone strength and bone density. In this study, we evaluated the effect of atorvastatin calcium on the flexural properties (3-point bending strength and modulus) of corticosteroid (methylprednisolone acetate) treated rabbit femurs and tibias. Our study hypothesis was that the use of statins would counteract the loss of bone strength caused by corticosteroid treatment. The 40 rabbits were divided into 5 groups: control, corticosteroid alone and corticosteroid combined with oral doses of atorvastatin calcium (2, 10, or 20 mg/day). A daily oral dose of atorvastatin calcium treatment for 70 days weakened the long bones of methylprednisolone acetate treated rabbits irrespective of the dosage (2, 10, or 20 mg). Cortical bone strength was assessed using the 3-point bending test at the end of the study period. A daily oral dose of atorvastatin calcium did not attenuate the loss of cortical bone strength caused by corticosteroid treatment in rabbits. It appeared to decrease that bone strength. If these results hold true in humans, they would have wide applicability given the frequent combined use of corticosteroids and statins in many patients.