Congenital Paradoxical Lower Eyelid Retraction With Upgaze due to an Anomalous Extraocular Muscle.

Congenital anomalous orbital structures are rare and associated with strabismus, globe retraction, and dystopia. The authors present a case of congenital paradoxical right lower eyelid retraction with upgaze due to an anomalous extraocular muscle in a 17-year-old, healthy, female patient. Orbital computed tomography showed an intraconal, inferolateral soft-tissue band extending from the orbital apex to the inferior oblique muscle and lower eyelid. There was resolution of lower eyelid retraction and exposure symptoms after resection of the anterior portion of the fibromuscular band from the lower eyelid retractors and eyelid elevation with ear cartilage. To the authors' knowledge, this case is the first to report anomalous orbital structure as a rare cause of congenital paradoxical lower eyelid retraction, which can be improved with resection.

John R. Ward, MD: Pioneer-Clinical Trials in Rheumatology.

John Robert Ward was one of the early academic rheumatologists in the United States. He was the founding father of rheumatology in the Intermountain West, the first Chief of the Division of Rheumatology in the Department of Internal Medicine at the University of Utah. Dr Ward became a national leader in the understanding and treatment of rheumatic disease. His foundational work established gold-standard techniques for the successful investigation of anti-rheumatic drugs. His leadership and scientific contributions clearly qualify him as a "giant in rheumatology."

Renal Neuroendocrine Tumor: A Case Report with Evaluation of Grading Criteria and Relationship with Carbonic Anhydrase 9 Immunoreactivity.

Neuroendocrine tumors (NETs) are only exceptionally primary to the kidney. At present, scant information is known regarding the behavior and prognosis of renal NETs, especially according to the assessment of grading parameters used for NETs originating from other more commonplace sites such as the pancreas and lungs. There are only rare reports of grade assessment in renal NETs, with most of these reports relying upon now antiquated World Health Organization gastroenteropancreatic and lung/thymus criteria. As an additional prognostic factor, positive CA9 staining in NETs may correlate with elevated grade, stage and risk of metastasis while serving as a potential target of chemotherapy and immunotherapy and indicator of Von Hippel-Lindau Syndrome. Rarer still are descriptions of renal NETs presenting with renal cell carcinoma in the ipsilateral or contralateral kidney. Thus, we present a patient with a primary renal NET of the right kidney with regional lymphovascular invasion and distant metastasis with an emphasis on grading criteria concordant with the World Health Organization 2022 gastroenteropancreatic and lung/thymus systems. In addition, we discuss unusual staining for CA9 in the patient's tumor and a concomitant left kidney clear cell renal cell carcinoma that may act as a clinicopathologic mimic of Von Hippel-Lindau Syndrome.

CHEK2 C1100del mutation associated with papillary renal cell carcinoma type II.

CHEK2 mutations have been noted in bone, brain, breast, colon, lung, thyroid, and prostate cancer. Although now reported in both clear cell and non-clear cell renal cancer, we have not found CHEK2 2 mutations reported in the papillary type II subtype (PRCC). Here, we report a 63-year-old female with a PRCC type II with a concomitant CHEK2 C1100del mutation, who is currently in complete remission three years post tumor resection.

Vascularized Sural Nerve Graft, Fascial Free Flap, and Regenerative Peripheral Nerve Interface in the Setting of Recurrent Thigh Liposarcoma: A Case Report.

Background: There is no clear consensus in the literature regarding clinical indications for vascularized nerve grafts. Most studies indicate that vascularized nerve grafting, rather than non-vascularized nerve grafting, is indicated for nerve gaps of greater than 7 cm. Vascularized nerve grafts are superior to non-vascularized nerve grafts because they possess an independent blood supply. However, not all nerve injuries can be repaired via vascularized nerve grafts. Methods: A 32-year-old female received a fascial free flap and vascularized sural nerve graft after having multiple reresections of a recurrent thigh liposarcoma. Results: A 25-cm segment of the sural nerve was isolated alongside the lesser saphenous vein and intervening fascia. The free fascial flap was subsequently reversed and placed into the thigh. Vascular anastomoses were created, and the sural nerve was anastomosed to the peroneal nerve. A small portion of muscle from the thigh was wrapped around tibial nerve fascicles of the sciatic nerve to create a regenerative nerve interface. Conclusions: Benefits of vascularized sural nerve graft compared with other vascularized nerve grafts include negligible sensory loss at the donor site and a nerve graft that can be designed on itself due to its vast length. Additionally, vascularized sural nerve grafts provided a better rate of axonal regeneration, rate of electromyographic return, and motor and sensory outcome compared with non-vascularized sural nerve grafts.

Selective angioembolization as a management strategy for angiomyolipoma causing urinary tract obstruction.

Angiomyolipoma (AML) is a benign renal tumor usually found incidentally. Rarely, AML can present with renal colic due to urinary tract obstruction. Prior cases of obstructing AML have been presented and managed successfully with surgical removal. Selective angioembolization has emerged as an alternative management strategy for AML, but no documented cases have been presented for this strategy in the setting of obstruction. Here, we present a case of obstructing AML treated with selective angioembolization with subsequent resolution of obstruction.

Recurrent hematochezia secondary to gastrointestinal stromal tumors (GISTs) in neurofibromatosis type one.

BACKGROUND: Patients with neurofibromatosis type 1 (NF1) suffer from cutaneous, neurological and intestinal complications due to the mutation of the neurofibromin gene and abnormal protein product. Gastrointestinal stromal tumors (GISTs) are relatively rare primary tumors of the stomach and small intestine. Patients with NF1 are prone to developing GISTs. We present a case of recurrent gastrointestinal (GI) bleeding from multiple GISTs in a patient with NF1. CASE: A 42 year-old male with NF1 presented with significant GI bleeding; endoscopies failed to identify the source. Multiple lesions involving the small bowel were seen on laparotomy; he underwent reparative small bowel resection. Pathology showed a well circumscribed spindle cell proliferation with minimal atypia and rare mitoses; immunostaining was positive for CD117 (KIT) and CD34; KIT mutations in exons 9, 11, 13 and 17 were negative. DISCUSSION: Up to 25% of patients with NF1 develop GISTs with non-specific presentations; however they may be a source of significant GI bleeding. The pathology, course and molecular composition of these tumors are different from sporadic GISTs. In NF1, GISTs are usually multiple, located in the small bowel (as opposed to the stomach as in sporadic cases) and occur at a younger age. Their clinical scenario is not unlike other hereditary tumor syndromes-multiple tumors with a 10-20% malignant potential. NF1-associated GISTs almost uniformly do not exhibit gain-of-function activation of KIT or PDGFA (pathogenesis is suggested to be from the loss of heterozygosity of the NF1 gene) and are not likely to respond to imatinib. Multiple means of localizing GISTs exist and capsule endoscopy should be recommended to all NF1 patients as it provides a non-invasive approach to localizing the tumors for further surgical management.

Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT.

BACKGROUND: Knee osteoarthritis (OA) is a major cause of pain and functional limitation in older adults, yet longer-term studies of medical treatment of OA are limited. OBJECTIVE: To evaluate the efficacy and safety of glucosamine and chondroitin sulphate (CS), alone or in combination, as well as celecoxib and placebo on painful knee OA over 2 years. METHODS: A 24-month, double-blind, placebo-controlled study, conducted at nine sites in the US ancillary to the Glucosamine/chondroitin Arthritis Intervention Trial, enrolled 662 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence grade 2 or 3 changes and baseline joint space width of at least 2 mm). This subset continued to receive their randomised treatment: glucosamine 500 mg three times daily, CS 400 mg three times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The primary outcome was a 20% reduction in Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain over 24 months. Secondary outcomes included an Outcome Measures in Rheumatology/Osteoarthritis Research Society International response and change from baseline in WOMAC pain and function. RESULTS: Compared with placebo, the odds of achieving a 20% reduction in WOMAC pain were celecoxib: 1.21, glucosamine: 1.16, combination glucosamine/CS: 0.83 and CS alone: 0.69, and were not statistically significant. CONCLUSIONS: Over 2 years, no treatment achieved a clinically important difference in WOMAC pain or function as compared with placebo. However, glucosamine and celecoxib showed beneficial but not significant trends. Adverse reactions were similar among treatment groups and serious adverse events were rare for all treatments.

Educational Case: Gallstones, Cholelithiasis, and Cholecystitis.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis.

BACKGROUND: Glucosamine and chondroitin sulfate are used to treat osteoarthritis. The multicenter, double-blind, placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis. METHODS: We randomly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily, 1200 mg of chondroitin sulfate daily, both glucosamine and chondroitin sulfate, 200 mg of celecoxib daily, or placebo for 24 weeks. Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia. Assignment was stratified according to the severity of knee pain (mild [N=1229] vs. moderate to severe [N=354]). The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24. RESULTS: The mean age of the patients was 59 years, and 64 percent were women. Overall, glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent. As compared with the rate of response to placebo (60.1 percent), the rate of response to glucosamine was 3.9 percentage points higher (P=0.30), the rate of response to chondroitin sulfate was 5.3 percentage points higher (P=0.17), and the rate of response to combined treatment was 6.5 percentage points higher (P=0.09). The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group (P=0.008). For patients with moderate-to-severe pain at baseline, the rate of response was significantly higher with combined therapy than with placebo (79.2 percent vs. 54.3 percent, P=0.002). Adverse events were mild, infrequent, and evenly distributed among the groups. CONCLUSIONS: Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee. Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain. (ClinicalTrials.gov number, NCT00032890.).

Two-dimensional echocardiographic findings of pulmonary valve cyst secondary to pulmonary valvuloplasty.

Real time two-dimensional transthoracic and transesophageal echocardiography demonstrated a mobile echolucent mass attached to the pulmonary valve in a 25-year-old adult, 20 years following balloon pulmonary valvuloplasty. The mass was surgically excised and pathology showed it to be a cyst.

Blunt testicular trauma results in rupture of mixed germ cell tumor.

It is extremely rare that a documented case of blunt trauma results in rupture of a testicular tumor. We present the case of a 24-year-old man who was crushed by a tree who developed spontaneous testicular rupture. At surgical exploration, he was found to ultimately have a mixed germ cell tumor of the testicle. This case illustrates the importance of physical examination, patient clinical history, and scrotal ultrasound in the management of scrotal trauma. In this instance, the testicular mass ruptured and lead to significant testicular hemorrhage.

Middle ear choristoma presenting as cholesteatoma with conductive hearing loss.

A 6-year-old male was seen for evaluation of middle ear polyp with associated hearing loss and otorrhea. CT scan revealed canal polyp with a stalk extending to the middle ear with malformation of the malleus and incus. The patient underwent exploratory tympanotomy which revealed a fistula from the bony-cartilaginous junction connecting to a middle ear mass which had eroded the incus. Intraoperative pathology suggested columnar epithelium without cholesteatoma or muscle. Final pathologic diagnosis reported dense fibrous tissue as well as ectopic salivary gland tissue, consistent with salivary gland choristoma. After removal of the mass, a partial prosthesis was successfully placed. Middle ear salivary gland choristoma is a rare entity. It can be confused clinically with cholesteatoma and is usually diagnosed on pathology. This diagnosis is often associated with other external, middle, and inner ear abnormalities.

Chromophobe renal cell carcinoma presenting as hemorrhagic shock: case report.

The majority of patients with chromophobe renal cell carcinoma (CRCC) are determined to be asymptomatic, with a small minority of patients having the classic triad of flank pain, hematuria, and abdominal mass. This case report describes a 56-year-old man first seen with hemorrhagic shock from retroperitoneal bleeding attributable to a large renal mass. An emergent exploratory laparotomy and radical nephrectomy were performed and the patient has since remained disease free at 3 year follow-up.

Chordoma of the anterior cranial fossa and ethmoids with orbital involvement.

PURPOSE: To report a case of orbital chordoma, emphasizing the clinical, operative, and histopathologic findings, and to review similar English-language reports. METHODS: This is a single case report with histopathologic correlation. Search of the English-language literature and review of referenced citations was performed. RESULTS: After treatment with resection and proton beam radiation, our patient is alive, without recurrence at 3-year follow-up. Biopsy of the recurrent tumor was consistent with chordoma. The original biopsy had S100 and pancytokeratin-positive tumor cells, with abundant clear to eosinophilic cytoplasm. Focal EMA positivity was present. Literature review identified 14 additional cases. CONCLUSION: Orbital chordoma is rare. Extraocular motility disturbances occur solely with intracranial lesions as well as those extending into the orbit, but globe displacement is the most common sign of orbital involvement. This tumor often recurs in the path of previous resection. Diagnosis is confirmed by distinctive histopathologic features and positive staining for S100, pancytokeratin, and EMA. Treatment and outcome analysis of orbital chordoma is difficult due to its rarity and lack of reported follow-up and may need to be extrapolated from reported skull base cases.

Cystic pancreatic neoplasms: an emerging problem.

Widespread usage of advanced abdominal imaging has resulted in an increased finding of cystic lesions in the pancreas in asymptomatic patients. Greater than 90% of cystic pancreatic lesions are of inflammatory origin, the well-known pancreatic pseudocysts. The critical issue confronting specialists is differentiating inflammatory lesions from neoplastic lesions.

Educational Case: Bladder Carcinoma In Situ.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

Educational Case: Fibroadenoma of the Breast.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

Giant calvarial intraosseous angiolipoma: a case report and review of the literature.

Intraosseous angiolipomas are very rare tumors occurring most commonly in the ribs and mandible. Only two cases with intracranial involvement have been reported in the literature. We report a case of a giant calvarial angiolipoma and its surgical treatment in a 30-year-old female who presented with a slowly expanding skull mass and discuss relevant radiological, histological and surgical findings.