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The COVID-19 pandemic created a unique challenge to health care systems, requiring rapid implementation of telemedicine services to provide continued care to patients while preserving personal protective equipment and decreasing the risk of disease transmission. Herein, we describe how our institution, an urban cancer center, utilized provider-to-provider telemedicine consultations (interprofessional e-consults) to provide subspecialty access to care to vulnerable patients in the epicenter of a global pandemic.

Background: Low-molecular-weight heparin has been the preferred treatment of cancer-associated thrombosis (CAT); however, emerging data support the use of direct oral anticoagulants (DOACs)., Objectives: The Memorial Sloan Kettering Cancer Center Clinical Pathway has served as the institutional guideline for the use of rivaroxaban to treat CAT since 2014. Key elements are to recommend against use of a DOAC in patients with active gastrointestinal (GI) or genitourinary tract lesions, and a prespecified dose reduction in the elderly (75+ years old). We present our institutional experience for treatment of CAT., Methods: From January 2014 through September 2016, 1072 patients began rivaroxaban treatment for CAT; 91.9% had a solid tumor, 8.1% had hematologic malignancies, and 75% of patients with solid tumors had metastatic disease. All patients with CAT treated with rivaroxaban were included in this analysis, regardless of adherence to the Clinical Pathway., Results: The 6-month cumulative incidence of recurrent venous thromboembolism and major bleeding were 4.2% (95% confidence interval [CI], 2.7%-5.7%) and 2.2% (95% CI, 1.1%-3.2%), respectively. The incidence of clinically relevant non-major bleeding leading to discontinuation of rivaroxaban for at least 7 days was 5.5% (95% CI,  3.7%-7.1%), and 73.3% of major bleeds occurred in the GI tract. The 6-month cumulative mortality rate was 22.2% (95% CI, 19.4%-24.9%). The elderly had similar rates of recurrent thrombosis and bleeding as those aged under 75 years., Conclusion: Our institutional experience suggests that in appropriately selected patients, rivaroxaban may be used for treatment of CAT with promising safety and efficacy.

Melanocytes may assume unique shapes and sizes but rarely have clear cytoplasm. We studied 28 melanocytic lesions that contained clear-cell melanocytes of the balloon-cell and sebocyte-like types. Clear-cell melanocytes were found more commonly in females (64%) than in males (36%), with predominance in females younger than 50 years (79%) and predominance in males older than 50 years (67%). They were distributed evenly throughout the body but were not found on acral sites. Clear-cell melanocytes were most prevalent in congenital nevi (18 or 72%) but were also found in 5 Clark nevi, 2 Meischer nevi, 1 Unna nevus, 1 atypical intra-epidermal proliferation, and 1 melanoma. The clear cells were distributed diffusely in 86% of the lesions and focally in 14%. The overall percentage of clear-cell melanocytes was 56%. The percentage of balloon cells was 57% and sebocyte-like melanocytes 32%. Clear cells with morphologic features of both balloon cells and sebocyte-like melanocytes, that is, intermediate cells, were present in all lesions with an overall percentage of 12%. The presence of melanocytes of both the balloon-cell and sebocyte-like types and the finding of clear-cell melanocytes with intermediate features in all lesions lends support to the theory that balloon-cell and sebocyte-like melanocytes may represent morphologic expressions of the same alteration in melanogenesis.

Introduction: Laparoscopic Heller myotomy has become the gold standard procedure for patients with achalasia. This study evaluates the clinical status, quality of life, and functional outcomes after laparoscopic Heller myotomy., Material and Methods: We analyzed patients who underwent laparoscopic Heller myotomy with an associated anti-reflux procedure from October 1998 to December 2010. Before surgery, we administered a clinical questionnaire and as of 2002, we also evaluated quality of life using a specific questionnaire (GIQLI). In 2011, we performed a follow up for all available patients. We administered the same clinical questionnaire and quality of life test as before surgery and performed manometry and 24-hour pH monitoring. According to the length of follow up, patients were divided into 3 groups. Group 1 with a follow-up between 6 and 47 months; group 2 follow-up between 48 and 119 months, and group 3 with a follow-up of more than 120 months). Moreover, 27 patients had already been evaluated with this same protocol in 2003. Pre- and postoperative data were compared for the 3 groups and for patients who completed follow up in 2003 and 2011., Results: Ninety-five patients underwent laparoscopic Heller myotomy. Seventy-six (80%) were available for follow-up. Mean follow-up was 56 months (range 6-143). Global improvement in dysphagia was 89%. Total DeMeester score decreased in the 3 groups. GIQLI scores improved after surgery, reaching normal values. Manometric determinations showed normal LES pressures after myotomy in the 3 groups. Ten percent of overall 24-hour pH monitoring was abnormal. The group of patients followed up in 2003 and in 2011 showed no impairment in the variables studied in the long term., Conclusions: Long-term follow up of the laparoscopic approach to achalasia showed good results concerning clinical status and quality of life, with normal sphincteric pressures and a low incidence of gastroesophageal reflux., (Copyright © 2013 AEC. Published by Elsevier Espana. All rights reserved.)

Background: There is limited previous research examining the healthcare costs of neovascular age-related macular degeneration (NV-AMD), which constrains our understanding of the economic impact of this condition. With aging populations, this leading cause of rapid vision loss in Western countries is expected to become a pressing health predicament, requiring decision makers to evaluate alternative treatment strategies for AMD., Objective: To document the economic burden of bilateral NV-AMD, the late stage of AMD, in elderly patients, from a societal perspective. STUDY DESIGN, SETTING AND PARTICIPANTS: A cross-sectional, observational study surveyed 401 patients with bilateral NV-AMD and 471 non-AMD subjects in Canada, France, Germany, Spain and the UK. Physicians' records and subjects' standardized telephone interviews were used to record medical resource utilization, assistance with daily living and social benefits. Annual bilateral NV-AMD-related socioeconomic costs were calculated in euro, year 2005 values., Main Outcome Measures: Societal costs including direct vision-related medical costs (e.g. treatment of AMD and vision-related equipment), direct non-vision-related medical costs (e.g. medications) and direct non-medical-related costs (e.g. home healthcare and social services) were the main outcome measures., Results: The demographic profile of NV-AMD patients was similar across countries; however, co-morbid condition profiles varied. NV-AMD patients reported substantial health-related problems and associated health resource utilization (HRU). In the previous 12 months, 12-22% of patients fell, and half of these patients required medical treatments. More than 20% (range 21-59%) of patients were prescribed vision-enhancing equipment. More than half of the patients (54-81%) were living with a spouse or family member and 19-41% reported receiving assistance for activities of daily living. The average annual societal cost per bilateral NV-AMD patient treated was estimated to be euro 7879 in Canada, euro 7349 in France, euro 12 445 in Germany, euro 5732 in Spain and euro 5300 in the UK, and direct vision-related medical costs accounted for 23-63% of the total cost. Half of the patients were diagnosed with bilateral NV-AMD for <1 year, with an average length of 5 months; there were no statistically significant differences in total annual costs per patient between these patients and those who were diagnosed with bilateral disease for > or =1 year. Estimated annual societal costs of bilateral NV-AMD patients in these countries ranged from euro 268 to euro 1311 million. Estimated annual societal costs of all NV-AMD patients in these countries ranged from euro 671 to euro 3278 million., Conclusions: Bilateral NV-AMD imposes significant functional impairment on patients, leading to increased HRU and a high societal cost burden. Differences in national healthcare systems and NV-AMD treatment patterns were reflected in the wide variation of NV-AMD costs across the five surveyed countries. Even though the prevalence rates and per-patient costs varied by country, the societal costs of NV-AMD patients were substantial in each country. Earlier intervention with effective therapies is expected to reduce disease burden and disability associated with NV-AMD and, thus, decrease the overall societal cost.

Background: Grover's disease (GD), or transient acantholytic dermatosis, is a pruritic, papulovesicular eruption characterized histopathologically by acantholysis with or without dyskeratosis. The origin of GD is unknown. Suggested causes include sweating, heat, immobilization occlusion, external beam and ultraviolet radiation, and xerosis. GD has also been found to occur in association with other diseases., Objective: Our aim was to assess whether GD exhibits seasonal variation and, if so, to determine whether any inferences can be drawn from its seasonal variation regarding its cause., Methods: We identified 385 patients who fulfilled both clinical and histopathologic criteria for GD among 423,106 patients diagnosed at the Ackerman Academy of Dermatopathology in New York City during the period from July 1, 1999 through June 30, 2004. By design, no hospitalized patients were studied., Results: A diagnosis of GD was given to 0.09% of biopsy specimens at the Ackerman Academy of Dermatopathology. GD was diagnosed approximately 4 times more commonly in winter than in summer, although the number of biopsies was constant. The average age of GD patients was 64 years with a male/female ratio of 1.95:1. The most common histopathologic type of GD was pemphigus vulgaris. GD was suspected clinically in 54% of patients., Limitations: This study did not assess hospitalized patients with GD or GD patients who lived outside the northeastern United States. Because the data assessed resided in a commercial dermatopathology laboratory, patients assessed in almost all cases had insurance coverage. Patients without insurance likely were not included in the study., Conclusions: The diagnosis of GD constitutes a higher proportion of biopsies in the winter than in the summer and therefore, by inference, occurs more frequently in the winter. In the winter, elderly men whose skin is naturally xerotic sweat less and are exposed to low ambient humidity. Rather than being caused by sweating and heat, GD arises against a backdrop of an intact but xerotic epidermis with decreased sweat production and is likely related to impaired epidermal integrity.

Background: Although the majority of melanomas demonstrate high rates of mutations in B-RAF or N-RAS that result in constitutive activation of the mitogen-activated protein kinase-signaling pathway, emerging data suggest molecular differences among melanoma subtypes. In this study, the authors evaluated the contribution of B-RAF and N-RAS mutations to the pathogenesis of Spitzoid melanomas., Methods: In total, 33 Spitzoid melanomas were analyzed for clinical and pathologic characteristics as well as for hot-spot mutations in the B-RAF and N-RAS genes. In the majority of patients (28 of 33 melanomas), the tumors were confined to the skin with no evidence of metastasis (average follow-up, 32.5 mos). There were five metastasizing melanomas (5 of 33 tumors) with regional or systemic spread., Results: Of 33 Spitzoid melanomas, only 1 showed the V600E mutation in the B-RAF gene (1 of 33 tumors; 3%). It was noteworthy that none of the metastatic Spitzoid melanomas (0 of 5 tumors; 0%), of which 2 resulted in fatal outcomes, demonstrated mutations in B-RAF or N-RAS., Conclusions: In contrast to the majority of cutaneous melanomas, activating hot-spot mutations in B-RAF or N-RAS were not involved in the pathogenesis of Spitzoid melanoma. These data suggested that Spitzoid melanoma is a distinct form of melanoma with unknown genes and/or signaling pathways involved in its development., (Copyright 2006 American Cancer Society.)

Tumours of the urinary bladder are rare in pregnancy. We report two such cases presenting with gross hematuria, but one of them was initially mistaken as vaginal bleeding. Patients age was 41 and 27 years old, at 26 and 18 weeks of gestation respectively. Diagnoses were made with cystoscopy and sonography. Tocolytics agents were employed. Both of the tumours were managed succesfully by transurethral electroresection. Raquianesthesia was employed in both. There were no adverse effects on the pregnacies. Transurethral resection is a safe procedure during pregnancy. The pathology diagnoses were inverted papilloma in the first case and papillary urothelial neoplasm of low malignant potential in the other one. The literature is reviewed.

Background: The success of Mohs surgery relies on the ability to histologically differentiate tumor from the normal background tissue of the patient. In most cases of basal cell carcinoma and nonmelanoma skin cancer, this is a relatively straightforward process. However, in distinction, when only subtle histopathologic features differentiate the background tissue from the tumor of interest, the determination of a tumor-free margin becomes more challenging., Objective: Our objective is to highlight the histopathologic features that we used to differentiate our patient's near-confluent background of trichoepitheliomas from the basal cell carcinoma that we were extirpating., Methods: Case report., Results: A 41-year-old white female with a history of familial multiple facial trichoepitheliomas presented for removal of a basal cell carcinoma on her right lower cutaneous lip. Mohs surgery was used to remove the tumor. The characteristic features of basal cell carcinoma and trichoepithelioma were used to differentiate the basal cell carcinoma that we were removing from the surrounding trichoepitheliomatous neoplasia., Conclusion: Mohs surgical extirpation of a basal cell carcinoma in a patient with multiple familial trichoepitheliomas requires a clear understanding of the histopathologic features that differentiate a trichoepithelioma from a basal cell carcinoma.

Background: Granular parakeratosis (originally termed axillary granular parakeratosis) is an idiopathic, benign, nondisabling cutaneous disease that manifests with intertriginous erythematous, brown or red, scaly or keratotic papules and plaques. It presents in all age groups and has no established clinical associations., Objectives: We wanted to assess the following: (1) the incidence of granular parakeratosis in biopsy specimens; (2) the differential diagnosis submitted with specimens requisition of granular parakeratosis; and (3) variations in its histopathology., Methods: Between July 1, 1999 and December 31, 2003, 363,343 specimens were submitted to The Ackerman Institute of Dermatopathology in New York. A computer search was done of these specimen records and cases diagnosed with granular parakeratosis were reviewed. A thickened stratum corneum with retention of keratohyalin granules was considered diagnostic of granular parakeratosis., Results: Eighteen of 363,343 specimens (0.005%) were diagnosed with granular parakeratosis. The diagnosis was confirmed by re-review of specimens. All lesions were located in the axillae. All patients were adults; most were women. In only one instance was the correct clinical diagnosis of granular parakeratosis submitted with a biopsy requisition of it. Granular parakeratosis is rare, if its incidence among biopsy specimens is representative of its true prevalence. The failure to include granular parakeratosis on biopsy requisition forms of granular parakeratosis specimens indicates that dermatologists are not familiar with it. Variations of the histopathology of the 18 cases occurred but did not correlate with the clinical impressions included on biopsy requisition forms.

Purpose: We sought to evaluate the detailed safety profile of photodynamic therapy with verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (ARMD) from the combined analysis of three multicenter, double-masked, placebo-controlled, randomized 24-month clinical trials of similar design (TAP Investigation Studies A and B and the VIP ARMD Trial), and to clarify the adverse reaction information in the current verteporfin product prescription information approved in the United States., Methods: Nine hundred forty-eight patients were randomly assigned to verteporfin or placebo. Treatment was administered as described in previous reports. All general entry criteria were similar, so systemic safety results were combined for this analysis. Entry criteria for CNV lesion composition and visual acuity in the two TAP Investigation trials was different from those used in the VIP ARMD trial, so ocular safety results for the treated eye were not combined., Results: The percentage of patients who experienced at least one ocular or nonocular adverse event, regardless of relationship to therapy, was similar between the verteporfin and placebo groups (92.3 and 89.1%, respectively, P = 0.114). The overall incidence of study eye adverse events was not significantly different between verteporfin and placebo. The only clinically relevant ocular adverse events reported with higher incidence after verteporfin compared with placebo were visual disturbances (22.1 versus 15.5% in TAP [P = 0.054] and 41.7 and 22.8% in VIP [P < 0.001]). Acute severe visual acuity decrease (defined as a visual acuity letter score decrease of at least 20, equivalent to at least four-line decrease, within 7 days of therapy) occurred in 3 patients treated with verteporfin in the TAP Investigation (0.7%) and 11 in the VIP ARMD trial (4.9%). Systemic adverse events with increased incidence after verteporfin compared with placebo, most of which were transient and mild or moderate, were injection site reactions (13.1 versus 5.6%; P < 0.001), photosensitivity reactions (2.4 versus 0.3%; P = 0.016), and infusion-related back pain (2.4 versus 0%; P = 0.004). No clinically relevant difference was observed between the verteporfin and placebo groups in any other adverse event., Conclusion: In 948 ARMD patients, verteporfin therapy had an overall safety profile similar to that for placebo, with a few exceptions. Visual disturbances, including acute severe visual acuity decrease, did not affect the net vision outcome benefits associated with treatment that has been reported previously. This detailed safety profile of verteporfin therapy clarifies the adverse reaction information in the current verteporfin product prescription information.

A 58-y-old man with chronic obstructive pulmonary disease (COPD) was admitted for treatment of an acute exacerbation of his illness. The patient's condition initially improved after therapy with oxygen, bronchodilators, antibiotic and methylprednisolone (40 mg every 8 h) was started. Soon afterwards, however, the patient's clinical status deteriorated and he died on the fifth hospital day. Post-mortem examination revealed unsuspected, isolated fungal myocarditis. The fungus was later identified as Aspergillus by indirect immunofluorescence. To our knowledge, this is the first case of fatal Aspergillus myocarditis related to short-term (< 1 week) steroid therapy in a COPD patient. We believe that this case provides further evidence to support the possibility of life-threatening infections in COPD patients who receive even a short course of corticosteroid treatment.

We analyzed the diagnosis of Pneumocystis carinii pneumonia by fiberoptic bronchoscopy in a large series of patients with the acquired immunodeficiency syndrome (AIDS). Transbronchial biopsy fragments, as opposed to endobronchial specimens, were found to have high diagnostic value. Their optimal number for diagnosis was determined by a simple statistical principle. It varied from a minimum of two in cases of severe pneumonia to a maximum of four when roentgenographic manifestations were altogether absent. The diagnostic yield of the transbronchial biopsy alone was 97 percent and that of "touch" preparations of the biopsies 88 percent; when both techniques were combined, the accuracy rose to 98 percent. By comparison, bronchial "washings" and "brushings" had a much lower yield, 59 percent and 57 percent, respectively. Because their diagnostic contribution was negligible, we conclude that the latter two procedures represent an unnecessary expense and waste of technical and professional effort.

The morphologic spectrum of intestinal metaplasia was studied in 49 gallbladders that had been excised because of cholelithiasis. Based on the absence or presence of endocrine cells, the cases of intestinal metaplasia were arbitrarily divided into two groups. The gallbladders from the first group (26 cases) contained isolated or small clusters of mature goblet cells, while those from the second group (23 cases), in addition to the goblet cells, contained argyrophil and argentaffin cells and, less frequently, Paneth cells and gland-like structures similar to colonic crypts. Pseudopyloric glands and superficial gastric-type epithelium were present in both groups. Argyrophil cells outnumbered argentaffin cells by a ratio of 4 to 1. By immunocytochemical methods serotonin-containing cells were found to be the most common endocrine cells. Other endocrine cells showed immunoreactivity for somatostatin, cholecystokinin, gastrin, and pancreatic polypeptide. The presence of gut endocrine cells and Paneth cells in the pseudopyloric glands suggests that these glands are also an integral component of intestinal metaplasia of the gallbladder. The findings support the hypothesis that cholelithiasis induces the appearance of a stem endodermal cell that, in turn, may differentiate into cells with mature intestinal or gastric phenotypes.

In the 1980s, under the impact of the acquired immune deficiency syndrome, Pneumocystis carinii Pneumonia (PCP) has become the prime infectious manifestation of this condition. In addition to the well-recognized "classic" features of this disease, several unusual manifestations are being recognized with increasing frequency. We presently review and illustrate the following "atypical" manifestations of PCP: (1) interstitial lung responses that include diffuse alveolar damage, bronchiolitis obliterans, interstitial fibrosis, and lymphoplasmacytic infiltrates; (2) striking localized processes frequently exhibiting granulomatous features; (3) extensive necrosis and cavitation; and (4) extrapulmonary dissemination of the disease. Close clinico-pathologic correlation and attention to roentgenographic detail are invaluable aids in arriving at the correct diagnosis.

Post-mortem examinations were conducted in 28 patients with the acquired immune deficiency syndrome (AIDS) and biopsy-proven Pneumocystis carinii pneumonia (PCP) who had been treated with trimethoprim-sulfamethoxazole (Bactrim, intravenous infusion [Roche]) and/or pentamidine isethionate. According to the evolution of the pulmonary process, the cases were classified into three groups. Group I ("fulminant" PCP) was composed of eight patients who died during the first week of the disease. Although treatment had eradicated most of the organisms, one third of the alveolar space volume, on the average, was filled by foamy exudates characteristic of PCP. This accounted for the respiratory insufficiency and death of these patients. Group II ("nonresolving" PCP) was comprised of nine patients who died within eight days and 2 months of diagnosis. PCP was less severe than in group I, but fatal respiratory insufficiency was the result of fibroblastic organization of the intraalveolar exudates (fibrosing alveolitis). In seven of the nine patients (78%), the latter resulted from oxygen toxicity; in the remaining two patients (22%) PCP, per se, was the original stimulus for the fibrosis. Patients in group II also had a high incidence of thromboembolic pulmonary lesions. Group III ("cured" PCP) was composed of 11 patients who responded dramatically well to therapy but died months or years later of other manifestations of AIDS. In group III patients, the roentgenographic picture at diagnosis was consistently less severe than in groups I and II.

Nodular regenerative hyperplasia of the liver is a rare pathologic condition that occurs in adults. We report three cases of this condition, including that of an infant with coexisting globoid cell leukodystrophy (Krabbe's disease). The literature on nodular regenerative hyperplasia of the liver is reviewed with emphasis on the role of drugs in the production of this disease.

Nodular regenerative hyperplasia of the liver is a rare condition that primarily affects adult patients. We report a case of this disease in a 4-month-old infant with coexisting globoid cell leukodystrophy (Krabbe's disease). Based on an analysis of this case and a review of the literature, we concluded that the two disorders were probably unrelated.