Primary Cutaneous Secretory Carcinoma: A Case Report and Literature Review.

Cutaneous secretory carcinomas (CSCs) are primary neoplasms of the skin that have been just recently described in the literature through case reports and series. In this case, a cutaneous lesion was found on the left temporal region of an 83-year-old male. He was referred to plastic surgery for complete excision, with negative margins confirmed by pathology. Histology, immunostaining, and genetic testing showed characteristics confirming the diagnosis of CSC and were supported by the information present in the current literature. Our patient showed no evidence of nodal disease or recurrence during regular follow-ups. Given the rarity of CSCs, we aim to present our experience regarding the diagnosis, pathological analysis, and management of our patient as well as summarize the present literature to further open avenues of research.

Durable Complete Remission With Combination of Stereotactic Body Radiation Therapy (SBRT) and Talimogene Laherparepvec (TVEC) Followed by Ipilimumab in Refractory Metastatic Melanoma.

Metastatic melanoma refractory to checkpoint inhibitors is a challenging clinical scenario. We present the case of a patient who was refractory to standard of care but was able to achieve a durable complete remission with the combination of stereotactic body radiation therapy (SBRT), talimogene laherparepvec (TVEC), and ipilimumab.

Case report: response to the ERK1/2 inhibitor ulixertinib in BRAF D594G cutaneous melanoma.

Melanoma is characterized by oncogenic mutations in pathways regulating cell growth, proliferation, and metabolism. Greater than 80% of primary melanoma cases harbor aberrant activation of the mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) pathway, with oncogenic mutations in BRAF, most notably BRAF V600E, being the most common. Significant progress has been made in BRAF-mutant melanoma using BRAF and MEK inhibitors; however, non-V600 BRAF mutations remain a challenge with limited treatment options. We report the case of an individual diagnosed with stage III BRAF D594G-mutant melanoma who experienced an extraordinary response to the ERK1/2 inhibitor ulixertinib as fourth-line therapy. Ulixertinib was obtained via an intermediate expanded access protocol with unique flexibility to permit both single-agent and combination treatments, dose adjustments, breaks in treatment to undergo surgery, and long-term preventive treatment following surgical resection offering this patient the potential for curative treatment.

Cutaneous Carcinosarcoma: A Small Case Series and Review of the Literature of a Rare Skin Tumor.

Carcinosarcomas are composed of epithelial and mesenchymal elements and primarily present within visceral organs. Despite being potentially aggressive, they are a rare diagnosis in the skin, and few manifestations have been reported to date. In this report, we describe two separate cases of carcinosarcoma presenting as nonhealing scalp wounds. Patient A: a 57-year-old male with a nonhealing skin lesion of ten years successfully treated with wide-local excision and local ortichochea flap reconstruction. Patient B: a 75-year-old female that presented with a painless, slow-growing hemorrhagic mass of 7 years invading the skull and dura ultimately requiring craniectomy and free-tissue transfer with anterolateral thigh flap. Cutaneous carcinosarcomas have more favorable outcomes due to low metastatic rates likely due to earlier detection, but delayed presentation can be fatal. Histopathological analysis is critical for determining diagnosis and prognosis. Adequate reconstruction after wide base excision varies and follows the reconstructive ladder/elevator ranging from primary closure up through free-tissue transfer. With cutaneous manifestations of carcinosarcoma seldom reported in the literature, it is our hope that reporting unusual instances such as this will raise awareness and allow for earlier diagnoses, treatments, and reconstructions.

Extrapleural Superficial Solitary Fibrous Tumor on the Posterior Shoulder: A Case Report and Review of the Literature.

Objective: Mesenchymal in origin, solitary fibrous tumors are primarily seen within the pleura of the lung or in serosal-lined body cavities. Constituting 1% to 2% of all soft-tissue tumors, solitary fibrous tumors are rare entities, especially when found in extrapleural and in superficial locations. A review of PubMed MEDLINE literature for superficial solitary fibrous tumors revealed 71 reports in case reports and small case series. Methods: In this report, we describe a 74-year-old man with an extrapleural superficial solitary fibrous tumor, as well as present a review of the current published literature to date. Results: We present the clinical course, surgical procedure, histopathological features, and treatment options, as well as present a compilation of the published data on superficial solitary fibrous tumors. Conclusions: Based on the current literature, solitary fibrous tumors are more common in middle-aged women and in the head and neck region. Diagnosis of solitary fibrous tumors requires tissue sampling and staining for immunohistochemical markers. Management of these tumors is based on wide local excision with histologically negative margins. If negative margins cannot be surgically achieved, adjuvant therapies including radiation have been described. With extrapleural manifestations of solitary fibrous tumors seldom reported in the literature, it is our hope that reporting these unusual instances will raise awareness of such disease manifestations and allow for earlier diagnosis and treatment.

A legacy of struggle: the OSHA ergonomics standard and beyond, Part I.

In November 2000, the Occupational Safety and Health Administration (OSHA) issued an ergonomics standard to prevent debilitating work-related musculoskeletal disorders (WMSDs). It was rescinded by Congress within four months. We explore how this story unfolded over two decades of collaboration and conflict. Part I provides an overview of the historical context of the struggle for a standard, followed by interviews with key players from labor, academia and government. They provide a snapshot of the standard; discuss the prevalence of WMSDs in the context of changing work organization; give insight into the role of unions and of scientific debate within the context of rulemaking; and uncover the basis for the groundbreaking OSHA citations that laid the foundation for a standard. Part II interviews further explore the anti-regulatory political landscape of the 1990s that led to repeal of the standard, discuss the impact of the struggle beyond the standard, and describe creative approaches for the future.

A legacy of struggle: the OSHA ergonomics standard and beyond, Part II.

The OSHA ergonomics standard issued in 2000 was repealed within four months through a Congressional resolution that limits future ergonomics rulemaking. This section continues the conversation initiated in Part I, documenting a legacy of struggle for an ergonomics standard through the voices of eight labor, academic, and government key informants. Part I summarized important components of the standard; described the convergence of labor activism, research, and government action that laid the foundation for a standard; and highlighted the debates that characterized the rulemaking process. Part II explores the anti-regulatory political landscape of the 1990s, as well as the key opponents, power dynamics, and legal maneuvers that led to repeal of the standard. This section also describes the impact of the ergonomics struggle beyond the standard itself and ends with a discussion of creative state-level policy initiatives and coalition approaches to prevent work-related musculoskeletal disorders (WMSDs) in today's sociopolitical context.

NM-23 gene loss of heterozygosity and protein expression in high-stage laryngeal squamous cell carcinomas.

Tumor suppressor genes that reduce metastatic potential have been described in a variety of different tumor types. One of the main tumor metastasis suppressor genes is nm-23, which is a nucleoside diphosphate kinase. Two isotypes, nm-23H1 and nm-23H2, have been cloned and map to chromosome 17q21.3. In a variety of tumors, including colon cancer and breast cancer, loss of expression of nm-23 is associated with lymph node metastasis. In other organ systems, however, this relationship is not seen. In head and neck squamous cell carcinomas (HNSCC), there have been conflicting results regarding the association between nm-23 protein expression and metastatic potential. To further explore the tumor metastasis suppressor function of nm-23 in HNSCC, we studied high-stage laryngeal carcinomas, tumors with and without cervical lymph node metastasis for nm-23 protein expression and loss of heterozygosity of the gene locus. Twenty-five cases were included (11 cases with and 14 cases without metastasis). Loss of heterozygosity for the nm-23 gene locus was seen in 7 of 22 (32%) informative tumors. Using immunohistochemistry, most tumors expressed nm-23, though decreased expression was seen in 10 of 25 (40%) cases. Only 2 tumors showed negative expression. We did not find a correlation between either protein expression or loss of heterozygosity with metastatic disease or any other adverse prognostic factors in this group of high-stage laryngeal squamous cell carcinomas. These data imply that nm-23 may be tumor suppressor gene involved in HNSCC but that it may not function as a tumor metastasis suppressor in high-stage laryngeal carcinoma.

Comparative mutational analysis of pulmonary scar epithelium, bronchioloalveolar carcinomas, and invasive well-differentiated pulmonary adenocarcinomas: a molecular approach to diagnostically challenging cases.

Discrimination of invasive well-differentiated adenocarcinoma (IAD) from reactive bronchioloalveolar epithelium entrapped in pulmonary scars (PSE) may be difficult on routine histology, especially on small biopsies. Ancillary studies to help in this regard are desirable. Whereas IADs have been shown to harbor cumulative mutational damage of tumor suppressor genes, little is known about molecular changes in PSEs. In this study, we compared cumulative loss of heterozygosity (LOH) of tumor suppressor genes in PSEs (N = 12), bronchioloalveolar carcinomas (BACs, N = 15) and stage 1 IADs (N = 7). Unstained serial sections were microdissected to obtain lesional and normal tissue DNA. PCR was performed for up to 16 polymorphic markers. An allelic ratio of < 0.5 or >2.0 was designated as LOH. Fractional allelic loss (FAL) was calculated for each case as the number of markers with LOH divided by the total number of informative markers. Mean percentage of informative markers was 76.8%. PSEs showed significantly lower mean FAL compared with BACs and IADs (3.0% vs. 20.4% and 28.5%, respectively; P < 0.003). Only 1 case of PSE showed LOH of one marker in two different areas, whereas the majority of allelic losses in the neoplasms were present in two or more microdissected foci. Our study shows that PSEs harbor LOH of tumor suppressor genes at relatively low rates and in a random distribution compared with BACs and IADs, which show consistent allelic losses, and high FALs. These molecular differences may serve as an adjunct to histology in challenging glandular lesions of the lung.

Severe hemolysis resulting from D incompatibility in a case of ABO-identical liver transplant.

BACKGROUND: Hemolysis due to D incompatibility in the setting of liver transplantation is less frequent than that associated with ABO incompatibility, but can represent an equally adverse event. Approximately 10 percent of ABO-compatible liver transplants involve a D- donor and a D+ recipient. CASE REPORT: A case of severe D incompatibility resulting from liver transplantation in a 50-year-old O Rh+ man with end-stage liver disease who received an O Rh- liver allograft is reported. A declining hemoglobin level complicated the patient's postoperative course with laboratory evidence of anti-D-mediated hemolysis. Investigations revealed that the transplanted liver was from a female O Rh- donor with detectable antibodies against D, C, and K. The severity of the hemolytic anemia was such that the patient required two separate red blood cell (RBC) exchanges and intermittent RBC transfusions over the course of almost a year. In addition to the use of RBCs negative for D, C, and K, the patient underwent a variety of B-cell suppressive therapies including glucocorticosteroids, mycophenolate mofetil, and rituximab. A normalization of hemoglobin levels and a decrease in serum bilirubin did not occur until after a splenectomy on postoperative Day 321. CONCLUSION: This represents the sixth and most severe case reported of hemolysis resulting from D incompatibility in liver transplantation. When unexpected serologic findings are identified in a transplant recipient, obtaining more information on the donor may help guide transfusion support.

p63 expression in assessment of bronchioloalveolar proliferations of the lung.

Discrimination of well-differentiated pulmonary adenocarcinoma from reactive bronchioloalveolar epithelium can be difficult on routine histology, especially with small biopsies. Ancillary studies to help in this distinction are desirable. p63, a p53-homologous nuclear protein, is a marker of reserve cells of the bronchus and terminal lobular unit. In this study, 33 cases of adenocarcinoma (20 open lung and 13 transbronchial/percutaneous biopsies) and 43 cases of benign lungs with fibrosis and metaplasia (22 open lung and 21 transbronchial/percutaneous biopsies) were studied for nuclear p63 expression by immunohistochemistry (Dako, Carpinteria, CA, USA). Five additional cases each of atypical adenomatous hyperplasia and adenosquamous carcinoma and three cases of squamous carcinoma (all open lung biopsies) were also stained. The diagnostic categories of benign lung conditions were usual interstitial pneumonia, parenchymal scar, cryptogenic organizing pneumonia and diffuse alveolar damage. In neoplastic cases, p63 positivity was calculated as percentage of all tumor cells examined. In areas of normal lung, p63 decorated the reserve cells of large and small airways and occasional cells of the distal lobular unit. In fibrotic reactive processes, an interrupted but distinct pattern of nuclear staining was present in all cases, with staining of basal cells of the airways as well as bronchiolar- and squamous-metaplastic epithelium (43/43, 100%). p63 immunoreactivity was less uniform in areas of acute lung injury within these cases. One adenocarcinoma and two cases of atypical adenomatous hyperplasia showed strong immunoreactivity (>80%), while three adenocarcinomas highlighted only rare tumor nuclei (<5% of tumor cells). Morphologic areas where p63 immunostaining was not helpful included the junction of normal lung and lepidic growth of adenocarcinoma, and retrograde spread of adenocarcinoma into small airways. Our results highlight the differential expression of p63 across various bronchioloalveolar lesions. Moreover, p63 may be helpful in distinguishing reactive from neoplastic glandular proliferations in the lung.

Molecular genotyping of medullary thyroid carcinoma can predict tumor recurrence.

Medullary thyroid carcinoma can have an aggressive behavior, and little is known about the molecular basis for clinical outcome. Defining risk of recurrent or metastatic disease is difficult, and it has been limited to clinical and pathologic features, such as advanced age, cervical lymph node metastases, and stage at presentation. Using microdissection and genotyping, we studied 11 cases of medullary carcinoma for allelic losses in a panel of known tumor suppressor genes. The tumor suppressor genes with the most frequent allelic losses were NF2, l-myc, and p53 (75%, 44%, and 44%, respectively). The average frequency of allelic loss across all tumors was 44% and was higher in tumors that recurred. A combination of previously described high-risk variables (increased patient age and cervical lymph node metastases) with the frequency of allelic loss yielded a high-risk group, in which 6 of 6 patients recurred, and a low-risk group, in which 0 of 5 patients recurred (P = 0.004). Frequency of allelic loss in tumor suppressor genes may provide a useful adjunctive prognostic test in medullary thyroid carcinoma.