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| Web: | mayocliniclabs.com |
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| Email: | mcl@mayo.edu |
| Telephone: | 800-533-1710 |
| International: | +1 855-379-3115 |
| Values are valid only on day of printing | |
55 year old male with a right lower lobe lung mass. The mass is composed of a mixture of round cells with uniform nuclei, fine chromatin and monomorphic spindle cells. The cells are positive for CD56, CD117, TLE1 and BCOR. The cells are negative for DOG1, cytokeratins, synaptophysin, chromogranin, S100, smooth muscle actin, HMB45, Melan-A, p40 and desmin.
The Correct Answer Is...
The correct answer is BCOR-CCNB3.
This is a case of a BCOR-IHCBCOR positive high-grade sarcoma which most commonly have BCOR-CCNB3 translocations. These sarcomas have a variable mixture of round cells that have uniform nuclei, fine chromatin pattern, and monomorphic spindle cells arranged in a fascicular pattern with variable myxoid stroma. These tumors were first described in 2012 and typically have a paracentric inversion on the short arm of chromosome X, resulting in the fusion of BCOR and CCNB3 that leads to the overexpression of CCNB3 (Cyclin B3).
The tumors arise almost exclusively in the soft tissue of young adult males and account for between 4% to 13% of undifferentiated small round cell sarcomas without an EWSR1 rearrangement. There are case reports of primary tumors in the paranasal sinus and lung. However, tumors in the soft tissue will also frequently metastasize to the lungs.
The IHC for BCOR is relatively sensitive/specific but molecular testing is required to confirm the diagnosis. BCOR tumors have a better outcome than CIC-DUX4 fusion tumors.
CIC-DUX4 typically show a higher degree of nuclear variability, with prominent nucleoli.
SS18-SSX is seen in synovial sarcoma which would be expected to be positive for TLE1 and rarely for BCOR by immunohistochemistry.
EWSR1-FLI1 is seen in ewing sarcoma which typically has a more uniform round cell appearance. However, a subset of cases of Ewing sarcoma can be positive for BCOR by IHC.
References
1. Am J Surg Pathol. 2017 Dec;41(12):1713-1721
2. Am J Surg Pathol. 2018 May ; 42(5): 604–615.
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Matthew Cecchini, M.D., Ph.D., F.R.C.P.C. Fellow, Pulmonary Pathology Mayo Clinic @Path_Matt |
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Joanne (Eunhee) Yi, M.D. Consultant, Anatomic Pathology Mayo Clinic Professor of Laboratory Medicine and Pathology Mayo Clinic College of Medicine and Science |
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Jorge Torres-Mora, M.D. Consultant, Anatomic Pathology Mayo Clinic Assistant Professor of Laboratory Medicine and Pathology Mayo Clinic College of Medicine and Science |
19 month old male was presented with frequent abdominal pains, constipation, sleep disorders, hyperactivity and high irritability. Upon evaluation, developmental delay for speech was also evident. Two of his older siblings, when younger had significant issues with attention deficit hyperactivity disorder (ADHD) but less severe than the patient.
The correct answer is...
Correct answer is Lead Toxicity.
Lead poisoning often presents with the nonspecific signs and symptoms such as abdominal pain, constipation, irritability, and anemia with individual variations. In the heme synthesis pathway, aminolevulinic acid dehydratase) is required for the conversion of aminolevulinic acid (sometimes denoted as ALA) to porphobilinogen and porphobilinogen deaminase helps in the conversion of porphobilinogen to porphyrins. Lead directly inhibits aminolevulinic acid dehydratase causing an impaired conversion of aminolevulinic acid to porphobilinogen. The result is an overproduction of aminolevulinic acid but normal levels of porphobilinogen. Acute intermittent porphyria is a rare autosomal dominant metabolic disorder caused from a deficiency of the porphobilinogen deaminase resulting in elevated levels of both aminolevulinic acid and porphobilinogen. Measurement of heme precursors in the urine such as aminolevulinic acid and porphobilinogen is crucial for the differential diagnosis between Lead poisoning and acute porphyria. In this case, since only the aminolevulinic acid and not the porphobilinogen were elevated, presence of acute porphyria was ruled out. One of the common and early clinical manifestations of lead poisoning includes irritability secondary to lead induced abdominal colic. Moreover, the patient’s abdominal pain was not specific to eating or drinking any dairy products, so the suspicion for lactose intolerance was eliminated. After exposure, most of the lead binds to the red blood cells and the rest is distributed to several organs such as liver, kidney and brain. Although causes for neurotoxicity is not clear, abnormal neural transmission due to oxidative stress and deregulated calcium signaling are some of the proposed mechanisms. Similar processes can also occur in the hepatic cells leading to its damage and release of transaminases into the blood stream. Buildings with chipping and peeling lead paint and lead dust from these materials isthe most common sources of lead exposure in young children. The use of lead paint in construction was banned in 1978 in the United States. High levels of lead can cause permanent brain dysfunction, behavioral disorders, attention deficits and hyperactivity. The patient’s family lived in an older construction with damaged lead paint, which was later identified as the cause of lead poisoning. This had resulted in similar but less severe outcomes in the older siblings. The landlord was informed to recheck and correct the source of exposure by the Minnesota Department of Health.References
1. T Venkatesh. Editorial role of a clinical biochemist in evaluating the impact of lead poisoning. Indian J Clin Bio chem. 2013;28(1):1–2.
2. JM Lamon. Clinical aspects of porphyrin measurement, other than lead poisoning. Clin Chem. 1977;23(2):260–63.
3. Castelbón Fernández FJ, Solares Fernandez I, Arranz Canales E, Enríquez de Salamanca Lorente R, Morales Conejo M. Protocol for Patients with Suspected Acute Porphyria. Rev Clin Esp. 2020; S0014-2565(20)30022-9.
4. Sanders, T., Liu, Y., Buchner, V., & Tchounwou, P. B. (2009). Neurotoxic effects and biomarkers of lead exposure: a review. Reviews on environmental health, 24(1), 15–45.
5. Protect Your Family from Sources of Lead - https://www.epa.gov/lead/protect-your-family-sources-lead.
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Vijayalakshmi (Viji) Nandakumar, Ph.D., M.S. Medical Director, Clinical Immunology, ARUP Laboratories Assistant Professor of Pathology, University of Utah Fellow, Clinical Chemistry, Mayo Clinic (2019-2020) |
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Joshua Bornhorst, Ph.D. Consultant, Clinical Biochemistry Mayo Clinic Assistant Professor of Laboratory Medicine and Pathology Mayo Clinic College of Medicine and Science |
A 60 year old male reported ongoing bone and joint pain that had left him immobile. The patient had a heart transplant 11 years prior and is on an immunosuppression regimen of cyclosporine, mycophenolate, and prednisone. He also takes voriconazole for a chronic pulmonary/ocular Aspergillus infection and is prescribed intermittent topical fluorouracil for actinic keratoses.
To investigate the bone pain symptoms, a plasma fluoride test was ordered.
The correct answer is...
The correct answer is Voriconazole.
Pulmonary aspergillosis, an infection of the lungs by fungi in the genus Asperillus typically requires lifelong anti-fungal therapy. Voriconazole, a triazole antifungal medication, is the first-line treatment for this disorder.1 It is thought that the fluoride atoms on voriconazole can be released into the body in some patients, leading an increase in blood fluoride level.2
High levels of fluoride increase osteoblast activity which in turn increases bone formation.3 However, the new bone that is created is more brittle and is more susceptible to fractures. The new bone is primarily fluoroapatite compared with normal bone which is composed of hydroxyapatite.4 The fluoride will also infiltrate tendons, ligaments, and muscles through mineral deposits.3 What is often seen is that patients with high fluoride levels exhibit periostitis and exostoses, which can explain this patient’s symptoms.4
When considering voriconazole-induced periostitis, three blood tests are ordered: voriconazole, alkaline phosphatase, and fluoride. High alkaline phosphatase is a good indicator of bone turnover. Interestingly, blood fluoride is one of the few blood tests that are performed using an ion-selective electrode (along with potassium, sodium, chloride, and calcium). Bone density scans may also be ordered to determine the extent of the periostitis, but may not always be performed on the areas most affecting the patient.
In this patient’s case, the alkaline phosphatase levels had been elevated for a prolonged period of time. His voriconazole levels were not higher than expected, but due to his prolonged treatment with the medication, high alkaline phosphatase, high fluoride level, and other clinical symptoms he was switched from voriconazole to itraconazole. Itraconazole, another antifungal medication useful for aspergillosis, notably does not contain any fluorine atoms in its chemical structure.5
References
1. Adwan, M. Voriconazole-induced periostitis: a new rheumatic disorder. Clinical Rheumatology, 2017;36:609-615
2. Wermers R, Cooper K, et al. Fluoride Excess and Periostitis in Translant Patients Receiving Long-Term Voriconazole Therapy. Clinical Infectious Diseases, 2011;52(5):604-611
3. Sellami M, Riahi H, et al. Skeletal fluorosis, don’t miss the diagnosis! Skeletal Radiology, 2020;49:345-357
4. Tan I, Lomasney L, et al. Spectrum of Voriconazole-Induced Periostitis With Review of the Differential Diagnosis. American Journal of Roentgenology, 2019;212:157-165
5. Thompson III G, Bays D, et al. Fluoride Excess in Coccidioidomycosis Patients Receiving Long-Term Antifungal Therapy: an Assessment of Currently Available Triazoles. Antimicrobial Agents and Chemotherapy, 2012;56(1):563-564
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Nicholas Larkey, Ph.D. Fellow, Clinical Chemistry Mayo Clinic @NicholasELarkey |
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Paul Jannetto, Ph.D. Consultant, Clinical Biochemistry Mayo Clinic Associate Professor of Laboratory Medicine and Pathology Mayo Clinic College of Medicine and Science |
6-Year-old male presented with dysphagia and hoarseness of voice for 3 months. Physical examination and laboratory work up were normal. Esophagram and esophagogastroduodenoscopy were performed and ruled out any anatomic abnormalities. Tissue biopsy showed normal esophagus, moderate chronic gastritis and mild chronic inflammation of the duodenum. Representative images are shown below.
The correct answer is...
The correct answer is Helicobacter heilmannii.
Helicobacter heilmannii is a gram negative rod, characterized by its large size (5–9 μm) and tightly coiled corkscrew appearance, unlike the smaller (3.5 μm) comma or slight spiral shape of H. pylori. In contrast to the low prevalence in humans, H. heilmannii infection is very common in dogs, cats, pigs, and nonhuman primates. Gastric biopsies from infected patients demonstrate chronic gastritis but generally less severe than in H. pylori gastritis. In clinical practice the typical morphologic features of the organisms on H&E are sufficient to establish a diagnosis of H. heilmannii chronic gastritis. Immunohistochemical stains of H. pylori can cross react with H. heilmannii further revealing its corkscrew-shaped appearance, larger size, and greater distance from the surface epithelium compared with H. pylori.
The importance of Helicobacter hepaticus to humans is not yet completely known. The bacterium is motile and gram negative, 0.2 to 0.3 µm in diameter, 1.5 to 5.0 µm long, and curved to spiral in shape. It colonizes the lower gastrointestinal tract, including the cecum, colon, and hepatobiliary system of mice. It has bipolar sheathed flagella (one at each end) but lacks the periplasmic fibers that envelope the bacterial cells in other Helicobacter species.
Campylobacter jejuni is a gram negative bacterium, comma or S shaped (with polar flagella), oxidase positive, and grows at 42°C. It is the major cause of bloody diarrhea, especially in children. Other clinical manifestations include fever, abdominal pain, and vomiting. Diagnosis of Campylobacter infection is usually established by stool culture.
References
1. APA Singhal, Anuradha V MD; Sepulveda, Antonia R MD, PhD Helicobacter Heilmannii Gastritis, The American Journal of Surgical Pathology: November 2005 - Volume 29 - Issue 11 - p 1537-1539 doi: 10.1097/01.pas.0000169499.96658.6e
2. Roehrl, Michael H A; Hernandez, Marier; Yang, Shi; Christensen, Thomas G; Morera, Claudio; Wang, Julia YHelicobacter heilmannii gastritis in a young patient with a pet: Gastrointestinal endoscopy, ISSN: 1097-6779, Vol: 76, Issue: 2, Page: 421-2 Publication Year: 2012
3. Fox JG, Dewhirst FE, Tully JG, Paster BJ, Yan L, Taylor NS, Yan N, Tayla NS, Collins MJ Jr, Govelick PL, Ward JM. Helicobacter hepaticus sp. nov., a microaerophilic bacterium isolated from livers and intestinal mucosal scrapings from mice. J Clin Microbiol 1994;32:1238–45.
4. Kaakoush NO, Castaño-Rodríguez N, Mitchell HM, Man SM. Global Epidemiology of Campylobacter Infection. Clin Microbiol Rev. 2015;28(3):687‐720. doi:10.1128/CMR.00006-15
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Mazen Osman, M.B., B.Ch. Resident, Anatomic and Clinical Pathology Mayo Clinic |
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Lizhi Zhang, M.D. Consultant, Anatomic Pathology Mayo Clinic Professor of Laboratory Medicine and Pathology Mayo Clinic College of Medicine and Science |
A 67-year-old man presented with abdominal pain. Esophagogastroduodenoscopy showed non-bleeding gastric ulcers. Biopsies of the stomach were performed.
The correct answer is...
The correct answer is Doxycycline-induced injury.
Many medications have been associated with medication-induced gastric injury. Some medications show a non-specific pattern of injury, but several drugs are associated with specific injury patterns in the stomach. Doxycycline is a tetracycline antibiotic that can cause characteristic patterns of injury in the stomach and esophagus.
In reported cases, endoscopic examination of the stomach shows yellow plaque-like lesions or non-bleeding ulcers. The microscopic features are similar to those in the presented case. Capillaries in the superficial lamina propria show degenerative change with eosinophilic necrosis of the vessel wall. The eosinophilic necrosis has a granular appearance and may be ring-like. Some involved blood vessels contain neutrophils or fibrin thrombi.There may also be associated superficial mucosal necrosis, foveolar hyperplasia, and lamina propria inflammation.
The differential diagnosis of doxycycline-induced gastric mucuosal injury includes gastric antral vascular ectasia (GAVE), small-vessel vasculitis, and amyloidosis. None of these diagnoses are associated with the characteristic granular eosinophilc vascular necrosis seen in doxycycline-induced injury. The following additional features also aid in the distinction from doxycycline-induced injury: In GAVE the endoscopic findings are typically restricted to the antrum. Amyloidosis can show eosinophilic material in the wall of blood vessels; however, amyloid is amorphous while the eosinophilic material in doxycycline-induced injury is more granular. A Congo red stain would also be negative in doxycycline-induced injury. Small vessel vasculitis would typically involve superficial and deep blood vessels.
The presence of eosinophilic vascular degeneration is relatively unique in the stomach and therefore should prompt the pathologist to consider the possibility of doxycycline-induced mucosal injury.
References
1. Shih AR, Lauwers GY, Misdraji J, et al. Vascular injury characterized doxycycline-induced upper gastrointestinal tract mucosal injury. Am J Surg Pathol. 2017;41:374-381.
2. Xiao SY, Zhao L, Hart J, et al. Doxycycline-induced gastric and esophageal mucosal injuries with vascular degeneration. Am J Surg Pathol. 2013;37:1115-1116.
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Daniel Rowan, M.D. Associate Consultant, Anatomic Pathology Fellow, Gastrointestinal and Liver Pathology (2019-2020) Mayo Clinic |
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Lizhi Zhang, M.D. Consultant, Anatomic Pathology Mayo Clinic Professor of Laboratory Medicine and Pathology Mayo Clinic College of Medicine and Science |
