UBXN2A suppresses the Rictor-mTORC2 signaling pathway, an established tumorigenic pathway in human colorectal cancer.

The mTORC2 pathway plays a critical role in promoting tumor progression in human colorectal cancer (CRC). The regulatory mechanisms for this signaling pathway are only partially understood. We previously identified UBXN2A as a novel tumor suppressor protein in CRCs and hypothesized that UBXN2A suppresses the mTORC2 pathway, thereby inhibiting CRC growth and metastasis. We first used murine models to show that haploinsufficiency of UBXN2A significantly increases colon tumorigenesis. Induction of UBXN2A reduces AKT phosphorylation downstream of the mTORC2 pathway, which is essential for a plethora of cellular processes, including cell migration. Meanwhile, mTORC1 activities remain unchanged in the presence of UBXN2A. Mechanistic studies revealed that UBXN2A targets Rictor protein, a key component of the mTORC2 complex, for 26S proteasomal degradation. A set of genetic, pharmacological, and rescue experiments showed that UBXN2A regulates cell proliferation, apoptosis, migration, and colon cancer stem cells (CSCs) in CRC. CRC patients with a high level of UBXN2A have significantly better survival, and high-grade CRC tissues exhibit decreased UBXN2A protein expression. A high level of UBXN2A in patient-derived xenografts and tumor organoids decreases Rictor protein and suppresses the mTORC2 pathway. These findings provide new insights into the functions of an ubiquitin-like protein by inhibiting a dominant oncogenic pathway in CRC.

Angioinvasive Fungal Thyroidits.

Fungal thyroiditis is an uncommon cause of thyroid inflammation and infection. This condition is typically observed within immunosuppressed patients, such as those with a hematologic malignancy or those receiving corticosteroids or chemo-radiation therapies. This report describes a case of a 66-year-old male with underlying high-risk myelodysplastic syndrome who presents with complaints of fever, right anterior neck pain, severe dysphagia, dysphonia, and difficulty managing upper airway secretions. A cervical computed tomography scan was performed and depicted a lowdensity area within the right thyroid lobe, infiltration of adjacent anterior fat tissue, and a retropharyngeal fluid collection. Ultrasound-guided biopsy and cytology revealed pauci-septate fungal hyphae with vascular invasion and abundant necrosis which is consistent with a diagnosis of angioinvasive fungal thyroiditis. This case demonstrates the importance of considering fungal species as a potential etiology in immunosuppressed patients with acute development of thyroiditis.

Sebaceous Adenocarcinoma in Parotid Gland of a 65-Year-Old.

Sebaceous adenocarcinoma of the parotid gland is a rare, malignant epithelial neoplasm with focal areas of sebaceous differentiation. A literature search revealed only 34 cases as of December 2020. Our case brings this total to 35. It is characterized as a partially encapsulated neoplasm with predominant areas of basaloid or squamous cells, and variable degrees of sebaceous differentiation. The sebocytes display an immunohistochemical staining pattern of EMA (cytoplasmic vesicles), CD15, lactoferrin, GCDFP-2, and androgen receptor positivity in the sebocytes. Bimodal peaks occur in the third and seventh decades of life. We present a case of sebaceous adenocarcinoma in a 65-year-old male who initially presented in the emergency department with hypertensive urgency and vertigo. MRI and CT scans showed a heterogeneous mass with a solid component and cystic areas, including calcifications that measured approximately 2.7 x 2.1 x 4.1 cm, predominantly in the deep part of the left parotid gland and extending upward to the adjacent sternocleidomastoid muscle and possibly infiltrating or abutting the muscle. Further questioning of the patient revealed a seven month history of a painless, slow-growing mass and increased sensation of fullness on the left side of his neck. Patient underwent a left total parotidectomy with flap reconstruction and left neck dissection, revealing a 6.0 x 4.4 x 2.2 cm left parotid gland with a 2.4 x 2.2 x 1.6 cm, well-circumscribed, multiloculated cystic mass that released red-brown serous fluid and thick yellow material and appeared to abut multiple resection margins. Microscopic examination showed nests of basaloid cells at the periphery and areas of distinct sebaceous differentiation, separated by bands of extensive hyalinization. The tumor also displayed an average of 2 mitotic figures per 10 high power fields, and less nuclear atypia and less invasiveness into the surrounding glandular tissue than what has been described in sebaceous adenocarcinomas. This is an unusual case because of the rarity of the tumor as well as the lack of nuclear atypia and invasiveness compared to what is described of sebaceous adenocarcinoma in the literature.

Aggressive Langerhans cell histiocytosis following T-cell acute lymphoblastic leukemia.

A 4-year-old female child developed cutaneous Langerhans cell histiocytosis 6 months following a diagnosis of T-cell acute lymphoblastic leukemia. Imaging revealed no evidence of systemic disease. Seven months later, the first systemic lesion was discovered on laryngoscopy. Restaging Positron Emission Tomography - Computed Tomography at that time revealed new 18-fluorodeoxyglucose-positive lesions in the left apical pleural margin, right lower peri-esophageal region, left ventricular myocardium, pancreas, upper pole of the left kidney, and inguinal and gluteal regions consistent with progressive systemic disease. Genomic testing revealed a low tumor mutational burden as well as mutations in KRAS G12A, ARID1A Q524, CDKN2A/B loss, and an alteration in NOTCH1.

Extramedullary Myeloid Sarcoma with Symptoms of Acute Pancreatitis Mimicking Pancreatic Carcinoma.

Extramedullary myeloid sarcomas are extramedullary tumors of immature myeloid cells, often associated with acute myeloid leukemia (AML), chronic myeloid leukemia (CML), or other myeloproliferative diseases. They are usually found in connective/soft tissues, skin, breast and gastrointestinal system. Pancreas is an uncommon site to be involved. We present a case of pancreatic myeloid sarcoma presenting with symptoms of acute pancreatitis including epigastric pain associated with nausea and vomiting, with imaging findings (abdominal CT) suggestive of pancreatic carcinoma, both presenting as hypoattenuating mass. It is important to consider myeloid sarcoma as a differential for pancreatic mass, especially given the history of AML as in our patient, which would lead to timely diagnosis and initiation of chemotherapy.

Epstein-Barr Virus Positive Mucocutaneous Ulcer: A Case Report.

Epstein-Barr virus (EBV) is known to be associated with B-cell lymphoproliferative disorders, and EBV-positive mucocutaneous ulcer (EBV-MCU) is a recently described entity observed in immunocompromised individuals. EBV-MCU is an aggressive appearing ulcerated lesion seen in the skin, oral cavity, and gastrointestinal tract. The process has Hodgkin-like features with a self-limited, indolent course, generally responding well to conservative management. We present a case of EBV-MCU recently encountered in a 54-year-old renal transplant recipient. She had persistent rectal pain and bleeding for over a year following hemorroidectomy. A large ulcer in the distal rectum with excoriation and granular margins was noted on examination, and an initial biopsy from the lesion was inconclusive. A repeat biopsy demonstrated ulcerated squamous and colonic mucosa with a polymorphic lymphoid infiltrate in the submucosa that contained large atypical cells. The large atypical cells were positive for PAX-5 and CD30 and demonstrated EBV RNA by in situ hybridization. EBV-MCU is a recently described occurrence in transplant patients, and awareness of this recently described entity is necessary for appropriate diagnosis and treatment.

Gone fishing: a unique histologic pattern in cutaneous angiosarcoma.

Cutaneous angiosarcoma is a rare but aggressive vascular malignancy that can present a diagnostic challenge due to a wide variety of clinical appearances and histologic features. Final diagnosis traditionally is yielded by corroborating the histologic and immunohistochemical findings with the clinical presentation; however, a histologic feature known as "fish in the creek," which consists of free-floating or tufted pleomorphic spindle cells within the vascular lumen, may be an additional diagnostic clue. In this study, we aimed to determine the diagnostic utility of this finding in cutaneous angiosarcoma. Our results suggest that "fish in the creek" has the potential to be an additional useful diagnostic tool for an otherwise challenging and deceptive malignancy.

A Rare Case of Lymphadenopathy: Kikuchi-Fujimoto Disease.

A relatively unknown cause of cervical lymphadenopathy is Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis. This is a rare and benign condition that presents with painful cervical lymphadenopathy, fevers, night sweats, and weight loss. This disease is most prevalent in Asian women between the age of 20-35 years. The diagnosis of Kikuchi Disease is made histologically and is characterized by paracortical areas of necrosis and a notable complete absence of neutrophils. The painful lymphadenopathy can be simply treated with antipyretics, but due to its presenting symptoms of Kikuchi disease, it is often mistaken for malignant lymphoma. As such, accurate diagnosis is required to avoid unnecessary testing. The evaluation of lymphadenopathy without an obvious cause can be quite challenging. When patients present with relapsing remitting lymphadenopathy, Kikuchi disease may warrant consideration.

The rapid A-Ci response: photosynthesis in the phenomic era.

Phenotyping for photosynthetic gas exchange parameters is limiting our ability to select plants for enhanced photosynthetic carbon gain and to assess plant function in current and future natural environments. This is due, in part, to the time required to generate estimates of the maximum rate of ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco) carboxylation (Vc,max ) and the maximal rate of electron transport (Jmax ) from the response of photosynthesis (A) to the CO2 concentration inside leaf air spaces (Ci ). To relieve this bottleneck, we developed a method for rapid photosynthetic carbon assimilation CO2 responses [rapid A-Ci response (RACiR)] utilizing non-steady-state measurements of gas exchange. Using high temporal resolution measurements under rapidly changing CO2 concentrations, we show that RACiR techniques can obtain measures of Vc,max and Jmax in ~5 min, and possibly even faster. This is a small fraction of the time required for even the most advanced gas exchange instrumentation. The RACiR technique, owing to its increased throughput, will allow for more rapid screening of crops, mutants and populations of plants in natural environments, bringing gas exchange into the phenomic era.

The world's biomes and primary production as a triple tragedy of the commons foraging game played among plants.

Plants appear to produce an excess of leaves, stems and roots beyond what would provide the most efficient harvest of available resources. One way to understand this overproduction of tissues is that excess tissue production provides a competitive advantage. Game theoretic models predict overproduction of all tissues compared with non-game theoretic models because they explicitly account for this indirect competitive benefit. Here, we present a simple game theoretic model of plants simultaneously competing to harvest carbon and nitrogen. In the model, a plant's fitness is influenced by its own leaf, stem and root production, and the tissue production of others, which produces a triple tragedy of the commons. Our model predicts (i) absolute net primary production when compared with two independent global datasets; (ii) the allocation relationships to leaf, stem and root tissues in one dataset; (iii) the global distribution of biome types and the plant functional types found within each biome; and (iv) ecosystem responses to nitrogen or carbon fertilization. Our game theoretic approach removes the need to define allocation or vegetation type a priori but instead lets these emerge from the model as evolutionarily stable strategies. We believe this to be the simplest possible model that can describe plant production.

Adequacy of powered vs manual bone marrow biopsy specimens: a retrospective review of sequential marrow aspirates and biopsies in 68 patients.

OBJECTIVES: To evaluate the quality and quantity of the bone marrow aspirates and biopsy specimens obtained with a powered system in comparison with the standard manual method. METHODS: The Pathology Laboratory Information System was reviewed for patients who had previously undergone bone marrow biopsies performed by both the OnControl Bone Marrow System and the manual method. A total of 136 cases (68 patients) were reviewed for adequacy and compared using an unpaired t test. RESULTS: The core biopsy specimens obtained by the OnControl system were significantly longer compared with those obtained by the manual system (16.9 vs 14.4 mm, P = .0036). However, the core biopsy specimens obtained by the manual method had on average more evaluable marrow elements (66% vs 40%, P < .0001), and the manual method was superior in 46 of the 68 cases when the length of evaluable marrow was calculated (9.7 vs 7 mm, P = .0049). CONCLUSIONS: Our findings show that longer core biopsy specimens are obtained by the OnControl Bone Marrow system but that the manual method is still superior when the percentage and length of evaluable bone marrow are analyzed.

Aggressive variant of a solid pseudopapillary neoplasm: a case report and literature review.

Solid pseudopapillary neoplasm, a lesion of uncertain cellular differentiation, is an unusual tumor of the pancreas with an indolent clinical course that typically arises in young females. We report a case of solid pseudopapillary neoplasm arising in a 17-year-old adolescent girl who presented with progressive abdominal pain. The patient underwent surgical resection of an 18 × 14 × 8-cm pancreatic mass that displayed the usual histologic features of a solid pseudopapillary neoplasm in addition to prominent nuclear atypia, increased proliferative index, and extensive necrosis. These unusual histologic findings are rare and are of particular interest owing to the dramatically decreased survival time displayed in this case. Although precise pathologic criteria suggesting a high risk for aggressive behavior of solid pseudopapillary neoplasms are uncertain, recognition of the unusual pathologic features displayed in this case may be useful in the prediction of potentially more aggressive neoplasms that portend a poorer prognosis.

Undifferentiated carcinoma of pancreas: a rare entity with aggressive behavior and possible genetic link.

UNLABELLED: An aggressive undifferentiated carcinoma of pancreas is a rare tumor, especially with a strong personal and family history of malignant melanoma. Limited literature review and few case reports described a genetic association between distinct types of pancreatic cancer and malignant melanoma. CASE REPORT: We present an uncommon case of an aggressive undifferentiated carcinoma of the pancreas in a 50-year-old Caucasian female. Initially, she presented with intermittent epigastric postprandial pain and mild nausea. A computed tomography scan of the abdomen showed a 5 cm heterogenous pancreatic tail mass, which on biopsy was found to be a poorly differentiated non-small cell carcinoma. Past medical history included malignant melanoma, with extensive family history of pancreatic cancer and malignant melanoma. However, not genetically confirmed, a hereditary pancreatic linkage was highly suspected. A week later, repeat computed tomography demonstrated tremendous enlargement of the pancreatic tail mass. Within a few weeks, the patient developed aggressive metastasis in various organ systems, followed by multiple surgeries. An emergent first round of chemotherapy was started, followed by an intensive care unit stay, and she eventually died. CONCLUSION: Our case exposes the aggressive behavior of undifferentiated carcinoma of pancreas, along with possible hereditary link between pancreatic cancer and malignant melanoma.

Usual clinical presentation of bizarre parosteal osteochondromatous proliferation (BPOP) with unusual histology.

Bizarre parosteal osteochondromatous proliferation (BPOP) or Nora's lesion is a unique, bony lesion that most often arises in the small bones of the hands and feet. The lesion was first described by Nora et al. in 1983, and documented cases have now shown the lesion to arise in the long bones, skull, maxilla and mandible. Radiographically, the bony lesion typically lacks a connection with the adjacent medullary cavity which is commonly seen with osteochondroma, the main differential diagnosis for Nora's lesion. Reported is the case of a 35-year-old male who presented to the orthopedic clinic after a non-painful mass arising on the right index finger was identified on routine physical examination. The lesion was surgically removed and sent for pathologic evaluation. Microscopic examination of the lesion revealed a disordered spindle cell proliferation and trabecular bone with no cartilaginous cap. The findings were believed to represent an osteocartilaginous neoplasm with radiographs and magnetic resonance imaging (MRI) suggestive of Nora's lesion. Thus, it was felt that the lesion fell within the overall spectrum of BPOP. The lesion is a unique entity that requires a complete history and physical exam along with radiographic and histologic analysis for proper identification. The lesion is benign but may be locally aggressive. Complete excision is the treatment of choice, and recurrence is common.

Ecosystem-level controls on root-rhizosphere respiration.

Recent advances in the partitioning of autotrophic from heterotrophic respiration processes in soils in conjunction with new high temporal resolution soil respiration data sets offer insights into biotic and environmental controls of respiration. Besides temperature, many emerging controlling factors have not yet been incorporated into ecosystem-scale models. We synthesize recent research that has partitioned soil respiration into its process components to evaluate effects of nitrogen, temperature and photosynthesis on autotrophic flux from soils at the ecosystem level. Despite the widely used temperature dependence of root respiration, gross primary productivity (GPP) can explain most patterns of ecosystem root respiration (and to some extent heterotrophic respiration) at within-season time-scales. Specifically, heterotrophi crespiration is influenced by a seasonally variable supply of recent photosynthetic products in the rhizosphere. The contribution of stored root carbon (C) to root respiratory fluxes also varied seasonally, partially decoupling the proportion of photosynthetic C driving root respiration. In order to reflect recent insights, new hierarchical models, which incorporate root respiration as a primary function of GPP and which respond to environmental variables by modifying Callocation belowground, are needed for better prediction of future ecosystem C sequestration.

Stored carbon partly fuels fine-root respiration but is not used for production of new fine roots.

The relative use of new photosynthate compared to stored carbon (C) for the production and maintenance of fine roots, and the rate of C turnover in heterogeneous fine-root populations, are poorly understood. We followed the relaxation of a (13)C tracer in fine roots in a Liquidambar styraciflua plantation at the conclusion of a free-air CO(2) enrichment experiment. Goals included quantifying the relative fractions of new photosynthate vs stored C used in root growth and root respiration, as well as the turnover rate of fine-root C fixed during [CO(2)] fumigation. New fine-root growth was largely from recent photosynthate, while nearly one-quarter of respired C was from a storage pool. Changes in the isotopic composition of the fine-root population over two full growing seasons indicated heterogeneous C pools; < 10% of root C had a residence time < 3 months, while a majority of root C had a residence time > 2 yr. Compared to a one-pool model, a two-pool model for C turnover in fine roots (with 5 and 0.37 yr(-1) turnover times) doubles the fine-root contribution to forest NPP (9-13%) and supports the 50% root-to-soil transfer rate often used in models.

Sani-cloth wipe mimics rare enzyme deficiency malonic aciduria on newborn screen.

Within a 7-month period at our institution, newborn screening by tandem mass spectrometry revealed 10 cases with elevated levels of malonylcarnitine, which suggested malonic aciduria. Malonic aciduria is a rare autosomal recessive inborn error of metabolism. Confirmatory testing yielded normal results in all the newborns involved. The application of quality improvement practices dictated investigating the dried blood spot collection process, which revealed the use of multiple blood-collection techniques by newborn nursery staff, improper handling of the dried blood spot specimens, and sanitary wipe contamination as the causes of the aberrant false-positive results at our institution. This systematic evaluation identified the cause of the aberrant false-positive results and a strategy was implemented to avoid aberrant results in the future. Thus far, no false-positive results have occurred since the investigative process. False-positive results on a newborn screen can cause unnecessary emotional and economic stress on families, a finding that was identified at our institution. Historically, false-positive newborn screening results have been identified in infants born by cesarean delivery in which iodine antiseptic was used and in newborns who receive total parenteral nutrition, such as premature infants in the NICU. Therefore, if an unusually high number of false-positive results are found during the newborn screening process, contamination should be considered as a contributing factor.