Previously, we described a disease syndrome in young turkeys caused by an enterovirus-like virus. The virus was designated an enterovirus-like virus based on size, morphology, and intracytoplasmic crystalline arrays of virus. In the present study, further characterization of the virus was performed to ascertain its classification. The virus has a buoyant density of 1.33 g/ml in CsCl and single-stranded RNA genome of approximately 7.5 kilobases. These combined characteristics indicate that this agent is an enterovirus.
To study the utility of the laminin immunostain in distinguishing invasive from noninvasive urothelial carcinoma (UC). The distinction is difficult but clinically significant as it can affect the decision to administer intravesical Bacillus Calmette-Guerin or can even lead to cystectomy.Representative sections of the transurethral resection of bladder tumor specimens from 25 cases of formalin-fixed paraffin-embedded invasive UCs and 25 cases of noninvasive UCs were selected for immunohistochemical (IHC) staining with laminin (Ventana, Oro Valley, AZ, USA). These cases were selected using a computer-assisted search of our laboratory information system (Cerner CoPath). Tissue from five paraffin-embedded tissue blocks containing unremarkable urothelial-lined bladder parenchyma was chosen as controls.All five control cases demonstrated crisp linear staining of the basement membrane underlying the unremarkable urothelium. Similar findings were also noted in the 25 cases of noninvasive UC. All 25 cases of the invasive UC demonstrated a complete absence of the staining around invasive and malignant urothelial cells. Laminin staining was also noted in both the muscularis mucosae and the detrusor muscle, although the pattern of staining in these areas was granular and was distinguishable from the crisp linear staining of the basement membrane.Laminin IHC staining can be useful in differentiating invasive from noninvasive UC.
To investigate the prognostic utility of multifocal extraprostatic extension (EPE) on biochemical recurrence after radical prostatectomy.We conducted retrospective analysis of biochemical recurrence and prognostic pathologic variables in 673 men with stage pT3a/pT3b prostate cancer from 2000 to 2012. Extent of EPE on radical prostatectomy was divided into three groups: focal EPE (tumor dimension <0.8 mm), established (≥ 0.8 mm), and multifocal (more than one focus of EPE <0.8 mm).Type of EPE had significant effect on recurrence with progressively lower progression-free probability and higher recurrence probability from focal to established to multifocal. Multifocal and established tumors exhibited worse prognostic features and higher hazard ratio than focal. In multivariate analysis, established and multifocal were independent prognostic factors with the greatest adverse prognostic significance associated with multifocal.Identification of multifocal EPE provides important prognostic information associated with increased likelihood of recurrence compared to focal and established tumors.
Ischemic fasciitis is a distinctive pseudosarcomatous entity with a marked predilection for elderly and physically debilitated or immobilized patients. The etiology of these lesions is unknown but felt to be related to ischemic vascular events.Herein, we report for the first time, two cytogenetic translocations, t(1;2)(p36.1;q23) and t(7;19)(q32;q13.3) in a 75 year-old ambulating female with a history of left total hip arthroplasty 20 years ago.These translocations suggest a possible clonal pathogenetic link though their significance remains to be established.
An 81-year-old woman presented to a physician who found a mass in the right breast. A mammogram performed 1 week prior to presentation showed a 7-mm solid lesion in the upper outer quadrant of the right breast, which was interpreted as “probably consistent with an old fibroadenoma.”Her medical and surgical history was noncontributory. There was no family history of cancer. The physical examination was remarkable for a 7-mm nodule present at approximately 9 o'clock within the right breast. No other dominant or discrete mass was present. No axillary or supraclavicular lymphadenopathy was noted. There was no evidence of a nipple discharge.An ultrasound-guided fine-needle aspiration (FNA) was performed with a 22-gauge needle in the radiologist's office. No immediate onsite evaluation of the aspirate was requested. Smears were air dried for Diff-Quik staining. Additional smears were prepared and immediately wet fixed in 95% ethanol for subsequent Papanicolaou staining. Cytopathologic examination of the FNA material showed hypercellular smears with predominantly cohesive fragments of proliferative epithelium. The tissue fragments showed a prominent branching, papillary architecture (Figure 1, Papanicolaou, original magnification ×100). Higher magnifications showed enlarged and crowded epithelial cells with overlapping hyperchromatic nuclei. Another prominent feature was the presence of discrete mucinous/myxoid stromal fragments in the background, giving the lesion a “biphasic” appearance (Figure 2, Papanicolaou, original magnification ×200). The cells within the stromal fragments were more discohesively arranged and bore a more fusiform-type appearance. Still higher magnifications showed the epithelial cells with round hyperchromatic nuclei and scant fragile cytoplasm attempting to form acinar-type structures with numerous fusiform stromal cells scattered in a mucinous background (Figure 3, Papanicolaou, original magnification ×400). An excisional biopsy of the right breast mass was subsequently performed. Gross examination showed a single fragment of firm pale white tissue measuring 1.2 × 0.7 × 0.5 cm, which was serially sectioned to show a nodular white parenchyma. The histologic sections showed a small well-circumscribed encapsulated nodule in the subcutaneous tissue. The nodule consisted of chords and nests of tubuloglandular structures within a myxoid and hyalinized stroma (Figure 4, hematoxylin-eosin, original magnification ×50).What is your diagnosis?Although the original cytopathologic diagnosis was thought to be “consistent with a fibroadenoma,” the histologic examination of the lesion confirmed the breast mass as a chondroid syringoma. The histologic features included glandular structures, solid or trabecular epithelial nests, cells with abundant hyaline cytoplasm, and a myxoid stromal background.Chondroid syringomas are rare benign adnexal, nonulcerated, nodular tumors with a characteristic myxoid cartilaginous matrix.1–3 Histologically, ultrastructurally, and immunohistochemically chondroid syringomas are analogous to the mixed tumor of the salivary glands (pleomorphic adenoma).2 The characteristic appearance of a chondroid or basophilic stroma with a tumor that seems benign is highly suggestive of chondroid syringoma. The tumor may be composed of large multilayered or elongated tubules of varying sizes and shapes. They tend to occur predominantly on the face, head, and neck but can occur on the trunk and extremities.2–5 The location may be entirely in the subcutis or rarely in the dermis. The epithelial components may form tubules with apocrine differentiation or have intracytoplasmic lumina of the eccrine type. They may have a proliferative fibroadenomatoid pattern, which was encountered in the present case.2–5Clinical and pathological characteristics of chondroid syringomas have been described in the breast.3–5 In all of the chondroid syringoma cases described in the literature, the subareolar region appears to be a common site for chondroid syringoma. Because of this subareolar location, an origin from a large breast duct has been suggested for these tumors.5–9 Immunohistochemical studies on chondroid syringomas have shown that the tumors stain for S100 protein and muscle-specific actin (myoepithelial cells) and cytokeratins. Electron microscopic studies have shown intermediate filaments with dense bodies and intercellular junctions. A myoepithelial cell role has been proposed in the histogenesis of this tumor.9 Although the histologic appearance of chondroid syringomas is quite distinct, chondroid syringomas share overlapping cytomorphologic characteristics with fibroadenomas on FNA, and an accurate distinction is not always possible. However, both chondroid syringomas and fibroadenomas are benign encapsulated tumors, and both are managed with limited tissue resection. Other cytologic differential diagnoses of chondroid syringoma include benign or malignant phyllodes tumor, colloid (mucinous) carcinoma, and metaplastic carcinoma. Although cytologic distinction could be difficult with a phyllodes tumor, the presence of a highly cellular stroma with cytologic atypia would favor the diagnosis of the phyllodes tumor over a chondroid syringoma. Likewise, colloid and metaplastic carcinomas would show a greater pleomorphism of the epithelium and the lack of a myoepithelial/stromal component in the smear background, as seen in chondroid syringomas.4–6Kanter and Sedeghi4 described the FNA cytology of a challenging case of chondroid syringoma of the breast. Although the cytologic appearance was identical to a salivary gland pleomorphic adenoma, diagnostic difficulties were encountered because mixed tumors are rare in the breast and because, in this particular case, there were clinical findings suggestive of malignancy.4 Other reports have described similar diagnostic difficulties.5–9In conclusion, chondroid syringoma is a rare benign tumor of the breast and may be confused with a number of benign and malignant tumors on FNA, particularly in the presence of suspicious clinicoradiologic findings. Although chondroid syringomas are extremely rare in the breast, an awareness of these benign lesions will help render an accurate diagnosis and prevent unnecessarily overaggressive surgery.
Context.—Central pathology review (CPR) was initially designed as a quality control measure. The potential of CPR in clinical trials was recognized as early as in the 1960s and quickly became embedded as an integral part of many clinical trials since. Objective.—To review the current experience with CPR in clinical trials, to summarize current developments in virtual microscopy, and to discuss the potential advantages and disadvantages of this technology in the context of CPR. Data Sources.—A PubMed (US National Library of Medicine) search for published studies was conducted, and the relevant articles were reviewed, accompanied by the authors' experience at their practicing institution. Conclusions.—The review of the available literature strongly suggests the growing importance of CPR both in the clinical trial setting as well as in second opinion cases. However, the currently applied approach significantly impedes efficient transfer of slides and patient data. Recent advances in imaging, digital microscopy, and Internet technologies suggest that the CPR process may be dramatically streamlined in the foreseeable future to allow for better diagnosis and quality assurance than ever before. In particular, whole slide imaging may play an important role in this process and result in a substantial reduction of the overall turnaround time required for slide review at the central location. Above all, this new approach may benefit the large clinical trials organized by oncology cooperative groups, since most of those trials involve complicated logistics owing to enrollment of large number of patients at several remotely located participating institutions.
Manufacturers of pathology imaging devices and associated software engage regulatory affairs and clinical affairs (RACA) throughout the Total Product Life Cycle (TPLC) of regulated products. A number of manufacturers, pathologists, and end users are not familiar with how RACA involvement benefits each stage of the TPLC. RACA professionals are important contributors to product development and deployment strategies because these professionals maintain an understanding of the scientific, technical, and clinical aspects of biomedical product regulation, as well as the relevant knowledge of regulatory requirements, policies, and market trends for both local and global regulations and standards. Defining a regulatory and clinical strategy at the beginning of product design enables early evaluation of risks and provides assurance that the collected evidence supports the product's clinical claims (e.g., in a marketing application), its safe and effective use, and potential reimbursement strategies. It is recommended to involve RACA early and throughout the TPLC to assist with navigating changes in the regulatory environment and dynamic diagnostic market. Here we outline how various stakeholders can utilize RACA to navigate the nuanced landscape behind the development and use of clinical diagnostic products. Collectively, this work emphasizes the critical importance of RACA as an integral part of product development and, thereby, sustained innovation.
