AMP Case Reports

March 2024—CAP TODAY and the Association for Molecular Pathology have teamed up to bring molecular case reports to CAP TODAY readers. AMP members write the reports using clinical cases from their own practices that show molecular testing’s important role in diagnosis, prognosis, and treatment. This month's report comes from Aga Khan University in Karachi, Pakistan. Case. An 87-year-old male with a clinical history of hypertension and sick sinus syndrome presented with a one-month history of fever, generalized weakness, and weight loss. There was no lymphadenopathy or hepatosplenomegaly on physical examination. Bone marrow examination was performed to evaluate for cytopenias.

CAP TODAY and the Association for Molecular Pathology have teamed up to bring molecular case reports to CAP TODAY readers. AMP members write the reports using clinical cases from their own practices that show molecular testing’s important role in diagnosis, prognosis, and treatment. The following report comes from Washington University School of Medicine in St. Louis. If you would like to submit a case report, please send an email to the AMP at amp@amp.org. For more information about the AMP and all previously published case reports, visit www.amp.org.

October 2023—Next-generation sequencing of tumor tissue has important implications in solid and hematologic malignancies because it can identify genomic variants that provide diagnostic, prognostic, and predictive information to guide clinical management. Variants identified on tumor sequencing can be classified as somatic (acquired after conception) or inherited through germline.

September 2023—CAP TODAY and the Association for Molecular Pathology have teamed up to bring molecular case reports to CAP TODAY readers. AMP members write the reports using clinical cases from their own practices that show molecular testing’s important role in diagnosis, prognosis, and treatment. The following report comes from Henry Ford Hospital. If you would like to submit a case report, please send an email to the AMP at amp@amp.org. For more information about the AMP and all previously published case reports, visit www.amp.org.

CAP TODAY and the Association for Molecular Pathology have teamed up to bring molecular case reports to CAP TODAY readers. AMP members write the reports using clinical cases from their own practices that show molecular testing’s important role in diagnosis, prognosis, and treatment. The following report comes from Washington University School of Medicine in St. Louis.

July 2023—A germline GATA2 c.121C>G (p.P41A) variant in a patient with an unusual acute promyelocytic leukemia CAP TODAY and the Association for Molecular Pathology have teamed up to bring molecular case reports to CAP TODAY readers. AMP members write the reports using clinical cases from their own practices that show molecular testing’s important role in diagnosis, prognosis, and treatment. The following report comes from Emory University School of Medicine. If you would like to submit a case report, please send an email to the AMP at amp@amp.org. For more information about the AMP and all previously published case reports, visit www.amp.org.

April 2022—Genetic alterations of the gene FLT3, especially internal tandem duplications in the juxtamembrane domain and point mutations in the tyrosine kinase domain, are commonly seen in patients with newly diagnosed myeloid leukemias. However, chromosome rearrangements involving the FLT3 gene are extremely rare in hematologic malignancies. The FLT3 gene has only a few known partner genes, including the gene ETV6, which encodes a transcriptional repressor. ETV6 has a wide variety of translocation partner genes, several of which are tyrosine kinase genes.

February 2022—Myeloproliferative neoplasms (MPNs) are a group of clonal hematopoietic stem cell disorders characterized by increased proliferation of myeloid cells of one or more lineage. The most common MPNs include chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). CML is defined by the BCR-ABL1 fusion, which typically results from the t(9;22)(q34;q11.2) rearrangement.

January 2022—A 33-year-old male with progressive hoarseness and shortness of breath was given a purported diagnosis of laryngeal papillomatosis and referred to our institution in November 2020 for a higher level of care. On presentation, the patient reported no recent upper respiratory infection-like systemic symptoms but had cough, nasal congestion, throat discomfort, dysphonia, and worsening dyspnea.

December 2021—Clinical metagenomic next-generation sequencing (mNGS), the comprehensive analysis of microbial and host genetic material (DNA and RNA) in patient samples, is increasingly available in clinical laboratories. At present, for various reasons including test complexity, cost, and turnaround time, this technology is generally limited to difficult-to-diagnose conditions where conventional microbiological testing methods may not lead to a definitive diagnosis in selected patients, such as those with meningoencephalitis of unknown etiology.

November 2021—Molecular analysis of advanced stage tumors has become the gold standard for identifying potential targetable mutations with high sensitivity, even in limited size tissue samples. However, when only tumor tissue is sequenced, it is difficult to differentiate between somatic mutations in the tumor cells versus constitutional (germline) mutations.

August 2021—Dermatitis herpetiformis (DH) is an autoimmune skin disorder associated with celiac disease and characterized by pruritic, blistering lesions mainly on the elbows, knees, buttocks, lower back, and scalp. Immunopathogenesis is attributed to IgA TG3 antibody immune complexes in the papillary dermis originating from subclinical celiac disease in the gut. Onset occurs at any age, but DH is diagnosed most often in young adults and rarely in children. Individuals of northern European heritage represent the most frequently affected population for DH, with an estimated incidence reported by the National Organization for Rare Disorders of 75.3 per 100,000 people. First-degree family members of patients with DH are at increased risk for both DH and celiac disease.

July 2021—The advent of genomically targeted therapy and immunotherapy has greatly altered the clinical management of advanced non-small cell lung cancer (NSCLC). Molecular testing is recommended for sensitizing EGFR mutations, ALK fusions, ROS1 fusions, BRAF V600E, NTRK fusions, RET fusions, and MET exon 14 skipping alterations.

April 2021—A 71-year-old female with a history of asthma and hypertension initially presented to her local hospital complaining of shortness of breath. She was found to be pancytopenic with severe anemia (hemoglobin 5 g/dL). She was subsequently transferred to a tertiary care facility for further evaluation. Bone marrow biopsy revealed a hypercellular marrow composed of 72 percent blasts. Flow cytometric analysis revealed a B-lymphoblast immunophenotype with expression of CD34, dim CD45, CD19, CD79a, CD22, HLA-DR, TDT, CD200, CD33, and dim CD13.

March 2021—Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is one of the most common lymphoproliferative diseases. It is a CD5-positive B-cell neoplasm of monomorphic small mature B cells. One of the characteristics of CLL/SLL is its heterogeneity, not only among individuals but also within individual patients.¹ The cytogenetic and molecular variants are dynamic during disease progression and in response to targeted therapies.

January 2021—Central nervous system high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR) is a rare and genetically distinct CNS neoplasm that occurs predominantly in the pediatric population. Previously, these tumors had been categorized as primitive neuroectodermal tumors of the central nervous system (CNS-PNET).

December 2020—Circulating cell-free DNA in the blood of pregnant women is derived from both maternal tissues and the placenta.¹ As a result, cfDNA isolated from maternal plasma can be used for noninvasive prenatal screening (NIPS) to identify fetal autosomal aneuploidies (trisomies 13, 18, and 21) and sex chromosome aneuploidies (SCAs). For fetal autosomal aneuploidies, NIPS offers higher detection rates and lower false-positive rates than traditional screening methods, such as maternal serum screening and nuchal translucency.² NIPS is the only screening option available for SCAs, such as Turner syndrome (45,X) and Klinefelter syndrome (47,XXY), which do not pre­sent with ambiguous genitalia on fetal ultrasound.³

November 2020—Pediatric-type follicular lymphoma (PTFL) is a rare form of lymphoma that was recognized as a new diagnostic entity in the revised 2016 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. The classic features of PTFL include male predominance, localized stage I lymphadenopathy, blastoid morphology, high proliferation index, and exceedingly good response rate to local excision.

October 2020—After 20 years of CAP advocacy, synoptic reporting in surgical pathology is ubiquitous. This came about in part by fiat and in part by all parties agreeing on the importance of standardization for patient care. The merits of some elements remain controversial. Molecular pathology, a newer discipline, does not offer the scope for creative writing once available in surgical pathology.

September 2020—A 64-year-old male presented with worsening shortness of breath, dry cough, and bilateral leg edema. He had a history of diabetes mellitus type two, hypertension, seropositive rheumatoid arthritis, and tobacco and alcohol abuse. CT scan demonstrated bilateral pleural effusions, pulmonary edema, subsegmental atelectasis, mildly enlarged hilar lymph nodes, mild cardiomegaly with a small pericardial effusion, and liver cirrhosis with a liver nodule. A hepatitis panel demonstrated positive serology for hepatitis C virus infection.

August 2020—Burkitt-like lymphoma with 11q aberration (BLL-11q) is a new provisional entity in the revised 2016 WHO classification of hematopoietic and lymphoid tumors.1 It refers to a subset of high-grade B-cell lymphomas that resemble Burkitt lymphoma with similar morphology, phenotype, and gene expression profiling, but lack MYC gene rearrangements. Instead, these lymphomas carry chromosome 11q proximal gains and telomeric losses, suggesting co-dysregulation of oncogenes and tumor suppressor genes.

June 2020—A middle-aged adult presented with shortness of breath and bruising and was found to have leukopenia (WBC 4.16 K/mcL; normal range 4.50–11.00 K/mcL) and anemia (Hgb 7.6 g/dL; normal range 12–16 g/dL) with rouleaux. The hypercellular bone marrow core biopsy (80–90 percent cellularity) contained 90 percent plasma cells of variable morphology, some with prominent nucleoli and occasional binucleate forms.

May 2020—Traditionally, histopathologic diagnosis has been regarded as the gold standard for most disease processes including cancer. However, in certain circumstances, a final histopathologic diagnosis cannot be rendered despite extensive conventional ancillary testing such as immunohistochemistry. In recent years, molecular testing has revealed specific variant signatures for many tumors, which can be used to determine a final diagnosis.

March 2020—Prader-Willi syndrome (PWS) is a rare genetic multisystem disorder with a reported incidence of approximately one in 15,000. It is characterized by severe infantile hypotonia with feeding problems, global developmental delay and mental deficiency, behavior problems, small hands and feet, hypogonadism and hyperphagia leading to marked obesity in early childhood, and a characteristic face.

February 2020—Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the proliferation of one or more of the myeloid lineages. Philadelphia chromosome-negative classical MPNs include polycythemia vera (PV), primary myelofibrosis (PMF), and essential thrombocythemia (ET).

December 2019—We report a case of a 34-week-gestation male infant with prenatal overgrowth born to a 19-year-old G1P0 mother. No significant family history or consanguinity were reported. The infant was delivered emergently by cesarean section due to pregnancy-induced hypertension and polyhydramnios.

October 2019—Primary intraocular lymphoma (PIOL) is a rare but aggressive B-cell malignancy usually considered as a subtype of primary central nervous system lymphoma. The most common form of PIOL is primary vitreoretinal lymphoma. PIOL is also known as the masquerade syndrome because it frequently mimics other ocular conditions such as chronic uveitis, which may be steroid-resistant. Its diagnosis is challenging and requires a high degree of suspicion. Here, we present a case of PIOL, the diagnosis of which was clinched based on the identification of a mutation in the myeloid differentiation factor 88 (MYD88) gene.

September 2019—Primary bladder adenocarcinoma is a rare vesicle malignancy accounting for up to two percent of malignant neoplasms of the bladder.¹ They occur in males more than females and are classically seen in the fifth or sixth decade of life.² Histologically they are of enteric, mucinous, or mixed types. Morphologically, the enteric type appears identical to a colonic adenocarcinoma and the mucinous type appears as neoplastic cells floating in pools of extravasated mucin. The mixed type is a mixture of the morphologies of the enteric and mucinous types. Immunohistochemically, adenocarcinomas of the urinary bladder classically express CK20 and CDX2.

August 2019–Newly discovered pathogenic variants in BCR-ABL1-negative myeloproliferative neoplasms (i.e. polycythemia vera, essential thrombocythemia, primary myelofibrosis) led to recent revisions of the World Health Organization diagnostic criteria. Initially JAK2 V617F, MPL (MPL W515K/L), and calreticulin (CALR) exon 9 gene pathogenic variants were deemed mutually exclusive in patients with essential thrombocythemia and primary myelofibrosis. However, coexisting somatic variants in both JAK2 V617F and CALR have been reported with variable frequency, ranging from less than one percent and up to 6.8 percent depending on the employed molecular technique.

May 2019—Non-small cell lung cancer patients with epidermal growth factor receptor activating mutations have excellent response to oral therapy with EGFR tyrosine kinase inhibitors. However, development of resistance to first- and second-generation TKIs is a well-recognized phenomenon with acquired p.T790M mutation and accounts for most TKI drug resistance. Resistance to EGFR TKI therapy has been described in tumors with coexistent primary p.T790M mutation and an EGFR activating mutation in a small number of patients.

April 2019—Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) in which promyelocytes predominate. APL accounts for about 10 percent of AML cases, and although APL can be diagnosed at any age, it is most common among young adults with a slight male predominance. APL is defined by the balanced reciprocal translocation (15;17)(q22;q21) between PML and RARA, although variant translocations involving RARA and other partner genes can occur.

March 2019—Colorectal cancer is the third most diagnosed cancer and the second highest cause of cancer mortality in men and women, and in 2016 it accounted for about nine percent of all diagnosed cancers in the United States. When CRC is detected at an early localized stage, the five-year survival rate is 90 percent. With progression to regional disease, five-year survival remains high, at 71 percent.

February 2019—Lung cancer is the second most commonly diagnosed malignancy and results in the most cancer-related deaths each year in the United States, but actionable aberrations in EGFR, ALK, ROS1, and other oncogenes are improving outcomes for a subset of patients.

January 2019—A 75-year-old woman with history of melanoma localized to the right forearm and status post excision six years prior presented with a two-month history of continuous left shoulder pain. She was managed initially with physical therapy and hydrocodone with no effect. Initial workup at an outside institution included an x-ray of the left shoulder that showed a destructive lytic lesion involving the proximal aspect of the left humerus associated with a pathologic fracture.