Anatomy of a Cyberattack: Part 1: Managing an Anatomic Pathology Laboratory During 25 Days of Downtime.

OBJECTIVES: Our institution was affected by a multi-institution, systemwide cyberattack that led to a complete shutdown of major patient care, operational, and communication systems. The attack affected our electronic health record (EHR) system, including all department-specific modules, the laboratory information system (LIS), pharmacy, scheduling, billing and coding, imaging software, internet access, and payroll. Downtime for the EHR lasted 25 days, while other systems were nonfunctional for more than 40 days, causing disruptions to patient care and significantly affecting our laboratories. As more institutions transition to network EHR systems, laboratories are increasingly vulnerable to cyberattack. This article focuses on the approaches we developed in the anatomic pathology (AP) laboratory to continue operations, consequences of the prolonged downtime, and strategies for the future. METHODS: Our AP laboratory developed manual processes for surgical and cytopathology processing, redeployed staff, and used resources within the department and of nearby facilities to regain and maintain operations. RESULTS: During the downtime, our AP laboratory processed 1,362 surgical pathology and consult cases as well as 299 cytology specimens and outsourced 1,308 surgical pathology and 1,250 cytology cases. CONCLUSIONS: Our laboratory successfully transitioned to downtime processes during a 25-day complete network outage. The crisis allowed for innovative approaches in managing resources.

Anatomy of a Cyberattack: Part 3: Coordination in Crisis, Development of an Incident Command Team, and Resident Education During Downtime.

OBJECTIVES: Our institution was subject to a multi-institutional, systemwide cyberattack that led to a complete shutdown of multiple major patient care, operational, and communication systems for more than 25 days. The electronic health record computer system was taken offline, as was the hospital email and authentication systems, internet access, and the laboratory information system. The impact on the hospital and patient care was substantial, and our laboratories were crippled. METHODS: Our laboratory endured challenges in communication because of the loss of connectivity and difficulties in laboratory management, and we recognized a need to restructure leadership to maintain operations during the crisis. As an academic institution, residents and trainees were also significantly affected by the disaster. RESULTS: We developed an incident command team (ICT), alternative methods of communication, and innovative management strategies to remain operational. Trainees were incorporated into the disaster-relief efforts, with negative impacts on resident education. CONCLUSIONS: This paper focuses on the challenges in communication and lab management as well as the need for an alternative leadership structure during the crisis. We also highlight the unique experience of our trainees during this prolonged downtime, underscoring the importance of incorporating resident trainees into the daily ICT's administrative activities as an invaluable lab management experience.

Diagnostic and management challenges for MDM2-, CDK4-negative fatty tumors of the retroperitoneum.

BACKGROUND: Neoplasms of the retroperitoneum that contain a major fat component may represent either benign entities, such as lipomas or angiomyolipomas, or malignancy such as liposarcoma. Distinguishing these diagnoses has important implications for management. While liposarcomas often stain positively for MDM2 and CDK4 proteins, absence of these markers can lead to diagnostic and management challenges. METHODS: We examined three cases in our institution of fat-containing masses of the retroperitoneum that lacked MDM2 and CDK4 markers to highlight the challenges in diagnosing and managing these cases. A thorough review of the literature examining radiologic and histologic features that can be used to determine that diagnosis was conducted and summarized. RESULTS: The three cases we present represent the three main diagnostic entities that can be found in among fatty tumors of the retroperitoneum: lipoma, angiomyolipoma, and liposarcoma. While radiologic features and analysis of histology helped to inform management, these cases in conjunction with the literature also illustrate the limitations of the diagnostic work up and importance also factoring the biologic behavior of the tumor in its management. CONCLUSION: Fat-containing tumors of the retroperitoneum that do not stain for MDM2 or CDK4 can pose a diagnostic challenge. Assessing radiologic and pathologic features in conjunction with the biologic behavior of these tumors should inform their management.

Selective vs Complete Sampling in Hysterectomy Specimens Performed for Atypical Hyperplasia.

OBJECTIVES: Atypical hyperplasia of the endometrium is a significant risk factor for uterine endometrioid carcinoma (EC) and an indication for hysterectomy. Standard sampling of these specimens includes evaluation of the entire endometrium to identify possible EC. We evaluated a method of selective sampling in an effort to balance resource utilization with diagnostic accuracy in the detection of EC. METHODS: Histologic diagnoses based on selective sampling (exclusion of every other block of endometrium) were compared with the original diagnosis based on complete sampling. RESULTS: Double-blinded review of these cases using selective sampling detected EC in 92% of hysterectomies, including all high-grade/high-stage carcinomas. Selective sampling had an 82% agreement with the original diagnoses, with most discordant diagnoses attributable to interobserver variability. Adjusting for interobserver variability increased diagnostic agreement between selective and complete sampling to 96%. CONCLUSIONS: Selective sampling is a feasible method to save time and resources while maintaining diagnostic accuracy.

Kaposiform hemangioendothelioma in multiple spinal levels without skin changes.

Kaposiform hemangioendothelioma is a rare vascular tumor of childhood that is locally aggressive but has little metastatic potential and by itself is not known to be lethal. It most commonly presents as a superficial or deep soft tissue mass with associated cutaneous lesions. Kasabach-Merritt phenomenon, a condition characterized by profound thrombocytopenia and life-threatening hemorrhage, often is associated with kaposiform hemangioendothelioma. Six cases of kaposiform hemangioendothelioma have been reported in bone, two of which were located in extracraniofacial bones. We report a diagnostically challenging case of a 6-year-old girl with kaposiform hemangioendothelioma of the thoracolumbar spine without Kasabach-Merritt phenomenon or cutaneous lesions.

D2-40 immunohistochemistry--so far!

D2-40 is a commercially available monoclonal antibody directed against human podoplanin, a transmembrane mucoprotein that is expressed in lymphatic endothelial cells. Since its introduction, D2-40 immunoexpression has been described in a variety of lymphovascular neoplasms including lymphangioma, Kaposi sarcoma, and hemangioendothelioma, as well as nonvascular neoplasms such as epithelioid mesothelioma, seminoma, and hemangioblastoma. More recently, D2-40 immunoexpression has been reported in primary adrenal cortical tumors, schwannomas, and adnexal tumors of the skin. This brief review provides an update on the ever-expanding proposed applications of D2-40 immunohistochemistry in surgical pathology.

Hepatic angiosarcoma five years following spontaneous intraperitoneal bleed of a hepatic mass.

Primary hepatic angiosarcoma is a rare and rapidly fatal disease. We present the highly unusual identification of this lesion five years after the initial clinical presentation.In 2003, a 32-year-old man presented with abdominal pain, tachycardia, and evidence of hemorrhage. A CT scan showed a hepatic mass with intralesional hemorrhage, intraperitoneal blood, and splenomegaly. The patient was stabilized clinically. Laparoscopic core biopsies demonstrated no malignancy, only findings consistent with an old hemorrhage. Contralateral lobe biopsies revealed normal liver tissue. A metastatic workup was negative and the decision was made to observe the patient clinically with radiographic follow-up, given his suspected portal hypertension based on thrombocytopenia and splenomegaly.Sequential imaging demonstrated a decrease in the size of the mass from 12.0 cm in 2003 to 3.0 cm in 2007. Subsequent newly identified esophageal varices prompted a reevaluation of the case. A repeat biopsy demonstrated a neoplasm of vascular etiology and uncertain malignant potential. By early 2008 the lesion had increased to 4.8 cm and was resected via a left hepatic lobectomy. An extremely vascular lesion with surrounding dense fibrosis was identified and pathologic examination demonstrated a high-grade angiosarcoma.We are unaware of any previous reports suggesting such a prolonged natural history of hepatic angiosarcoma. This case may represent the possibility of malignant transformation of a lower grade vascular neoplasm such as hepatic epithelioid hemangioendothelioma to an angiosarcoma.

Lithopedion: laparoscopic diagnosis and removal.

A lithopedion is an exceedingly rare obstetric phenomenon where the contents of an abdominal pregnancy calcify and become preserved. We present the case of a young woman undergoing laparoscopy for infertility during which a lithopedion was discovered.

p16INK4a immunoexpression: surrogate marker of high-risk HPV and high-grade cervical intraepithelial neoplasia.

p16INK4a has emerged as a valuable surrogate marker for high-risk human papillomavirus infection and shows increased immunoexpression with worsening grades of cervical intraepithelial neoplasia (CIN). Numerous studies have emerged in recent years supporting its role in the detection of high-grade dysplasia and have lead to the use of p16INK4a immunohistochemistry in many laboratories. However, only a few studies have examined the possible predictive or prognostic value of p16INK4a in CIN or cervical cancer. This review addresses some of the practical issues in the application of p16INK4a in everyday practice, with an emphasis on integrating the extensive data that have emerged in the literature on p16INK4a immunoreactivity in CIN. The potential role of p16INK4a immunohistochemistry in the prediction of CIN progression is also discussed.

Benign fibroblastic polyp of the colorectum.

GOALS: We present the clinicopathologic features, endoscopic appearance, and ultrastructure of a newly described mesenchymal polyp of the colorectum, termed benign fibroblastic polyp. STUDY: A total of 4 cases from our institution are analyzed using routine histopathology, immunohistochemistry, and electron microscopy, and compared with the original series of 14 cases previously described in the pathology literature. RESULTS: Benign fibroblastic polyps appear endoscopically throughout the colorectum as submucosal lesions with a hyperplastic surface component. These lesions are histologically and ultrastructurally distinct, but overlap with other mesenchymal polyps warrants additional immunohistochemical studies for definitive classification. CONCLUSIONS: Benign fibroblastic polyps of the colorectum comprise a recently described distinct entity of mesenchymal polyps that appear to follow an indolent clinical course. Their etiology is uncertain but may be linked to an exuberant tissue response following mucosal injury. Gastroenterologists should be aware of this new entity that will be increasingly diagnosed by pathologists.

p16INK4A immunoexpression and HPV in situ hybridization signal patterns: potential markers of high-grade cervical intraepithelial neoplasia.

Integration of human papillomavirus (HPV) into the cell genome is considered to be an important event in the progression of cervical neoplasia. p16, also a useful biomarker of cervical intraepithelial neoplasia (CIN), shows increased immunoexpression with worsening grades of CIN. This study examines the correlation between p16 immunoexpression, grade of CIN, HPV type, and HPV in situ hybridization diffuse and punctate signal patterns (linked to episomal and integrated viral particles, respectively) in 44 cervical biopsies/LEEP excisions classified as CIN 1 and CIN 2/3. In 22 of 25 (88%) CIN 1 lesions, p16 immunoexpression was confined to the lower half of the epithelium, with sporadic to focal staining in 11 of 25 cases (44%). In CIN 2/3 lesions, 15 of 17 (88.2%) showed diffuse, two-thirds to full-thickness staining of the epithelium. High-risk HPV types were found in 20 (80%) CIN 1 lesions and 17 (100%) CIN 2/3 lesions. Punctate signals were detected in only 3 (13.6%) of high-risk HPV-positive CIN 1 lesions and in 17 of 17 (100%) CIN 2/3 lesions (P<0.001). p16 immunoexpression and the presence of punctate signal on HPV in situ hybridization correlated with the degree of cervical neoplasia (P<0.001). However, 3 cases of CIN 1 demonstrating punctate signals did not demonstrate a comparable CIN 2/3 p16 staining pattern. Similarly, two CIN 1 lesions with comparable CIN 2/3 p16 staining showed no evidence of viral integration. Both increased p16 immunoexpression and punctate signal correlate with CIN 2/3 grade, supporting the use of either, or both, tests to confirm CIN 2/3. Strong p16 immunostaining in CIN 1 appears independent of HPV punctate signal type.

Splenic pregnancy: a case report and review of the literature.

Primary splenic pregnancy is the least common form of extrauterine pregnancy. We report a case of splenic pregnancy occurring in a 29-year-old woman presenting with acute abdomen and hemoperitoneum. Recognition of this rare form of gestation is of critical importance, owing to the risk of exsanguination and death, and should be considered in the differential diagnosis of acute abdomen in women of reproductive age.