Pathways Case Studies: June 2020

A 77 year old man presented with 6-8 weeks of right sided neck pain associated with a rapidly enlarging mass, fatigue, and night sweats. A fine needle aspiration of the 7.1 cm hypermetabolic mass showed acute and chronic inflammation. The diagnostic findings on histopathologic examination of an excisional biopsy are shown in the pictures below (Figure 1: H&E and Figure 2: GMS) and were consistent with findings on tissue culture and serologic studies. The patient reported frequent trips to Arizona.

	Rebecca Marrero Rolon, M.D. Fellow, Clinical Microbiology Mayo Clinic
	Bobbi Pritt, M.D. Division Chair, Clinical Microbiology Mayo Clinic Professor of Laboratory Medicine and Pathology Mayo Clinic College of Medicine and Science @ParasiteGal

A 52 year old female with congenital asplenia presented to the emergency department with altered mental status, difficulty communicating, and neck pain. This had been preceeded by three days of right ear fullness and malaise. A lumber puncture was performed, significant for an opening pressure of >50 cm H2O, 20,565 nucleated cells/µl with neutrophil predominance, glucose 1250 mg/dL. Gram stain of the cerebrospinal fluidis shown (Figure).

Kyle Rodino, Ph.D. Fellow, Clinical Microbiology Mayo Clinic @KGRodinoPhD

A previously healthy 15 month-old female presented to ED with persistent non-bloody non-bilious vomiting, fever, and edema. Her serum creatinine was elevated (2.62 mg/dL). CBC showed markedly low hemoglobin (6.1 g/dL), decreased platelet counts (71x109/L). Peripheral blood smear examination revealed marked schistocytosis, consistant with a thrombotic microangiopathy. Normal ADAMTS13 enzyme activity and negative PCR testing for Shiga-toxin supported a diagnosis of atypical hemolytic uremic syndrome (aHUS). Subsequent genetic testing identified a pathogenic variant in CFH (complement factor-H), and a variant of uncertain significance in CHFR5.

	Abdulrahman Saadalla, M.B., B.Ch. Resident, Clinical Pathology Mayo Clinic
	Ann Moyer, M.D., Ph.D. Consultant, Laboratory Genetics and Genomics Mayo Clinic Associate Professor of Laboratory Medicine and Pathology Mayo Clinic College of Medicine and Science

Methylation-sensitive multiplex ligation-dependent probe amplification (MLPA) was used for select family members of the pedigree shown here to test for the presence of large deletions, duplications and/or methylation defects in the imprinting control regions IC1 (H19) and IC2 (LIT1) on chromosome 11p15. The proband (IV-6) is a 21 month old female referred for genetic testing due to short stature along with growth and developmental delay.

	Laura Thompson, Ph.D. Fellow, Laboratory Genetics and Genomics Mayo Clinic
	Linda Hasadsri, M.D., Ph.D. Consultant, Laboratory Genetics and Genomics Mayo Clinic Assistant Professor of Laboratory Medicine and Pathology Mayo Clinic College of Medicine and Science

A 25-month-old female presented with eye deviation and ataxia and was found to have a large mass filling the fourth ventricle. The tumor was resected, and histopathological analysis showed a solid and papillary pattern of growth with poor differentiation, high mitotic activity, and areas of necrosis (Figure 1). The tumor also showed diffuse CAM5.2 immunostain, focal synaptophysin positivity, lacked expression of glial markers GFAP and Olig2, and showed loss of INI-1 and largely of H3 K27me3 expression. Overall, the tumor resembled a choroid plexus carcinoma. Tumor purity was morphologically estimated as 70%. Molecular and cytogenetic analyses were performed at the Mayo Clinic Genomics Laboratory. Neuro-oncology NGS testing showed a SMARCB1 mutation involving a canonical splice site in 84% of all sequencing reads (c.986+2T>G) (Figure 2). Chromosomal microarray identified losses along chromosomes 11 (including genes NUP98, IGF2, H19, and CDKN1C), 22 (including genes SMARCB1, MN1, NF2, EWSR1, and CHEK2), and X (Figure 3).

	Cinthya Jeanette Zepeda Mendoza, Ph.D. Fellow, Laboratory Genetics and Genomics Mayo Clinic
	Kandelaria (Ande) Rumilla, M.D. Consultant, Laboratory Genetics and Genomics Mayo Clinic Assistant Professor of Laboratory Medicine and Pathology Mayo Clinic College of Medicine and Science
	Caterina Giannini, M.D., Ph.D. Consultant, Anatomic Pathology Mayo Clinic Professor of Laboratory Medicine and Pathology Mayo Clinic College of Medicine and Science