bluuebunny/crossref_metadata_2025 huggingface dataset:
NUT Midline Carcinoma Mimics Anaplastic Thyroid Carcinoma
Authors: Chang Q , Li J , Tang S
Published: October 2021

Introduction/Objective

NUT carcinoma (NC) is an extremely rare, aggressive subtype of squamous cell carcinoma defined by rearrangement of the NUTM1 (aka NUT) gene. NC most commonly arises within the thorax and head and neck and predominantly affects teens and young adults. For the first time, we described a rare case of NC mimics anaplastic thyroid carcinoma.

Methods/Case Report

A 27-year female with no significant past medical history presented with neck pain and swelling for a few months and was noted to have a “thyroid” mass. An ultrasound guided fine needle aspiration of the mass showed a hypercellular specimen composed of highly atypical epithelial cells with irregular nuclear membrane and prominent nucleolus, high nuclear to cytoplasmic ration, dense cytoplasm, lying singly or in flat sheet mixed with acute inflammatory exudate (Fig. A, B). No thyroid follicular cells or colloid are present. It was signed out as suspicious for squamous cell carcinoma since there was no cell block for further workup. A following excisional biopsy demonstrated similar atypical epithelium detached or embedded in skeletal muscle and soft tissue with acute, chronic inflammation and necrosis (Fig C). By immunohistochemical stains, the atypical cells are positive for p40 (Fig D) and p53. The Ki-67 proliferation index is ranging from 40 % to 70 %. Scattered tumor cells are weakly positive for PAX-8 and TTF-1. These findings raise the possibility that the squamous cell carcinoma might be a component of anaplastic thyroid carcinoma. However, molecular studies revealed a NSD3-NUTM1 fusion, which is characteristically identified in a subtype of squamous cell carcinoma know as NUT “midline” carcinoma.

Results (if a Case Study enter NA)

NA

Conclusion

Diagnosis of NC can be established by positive NUT nuclear immunohistochemical staining. Recognizing the typical morphology and keeping low threshold for the NUT immunohistochemical staining will increase the diagnostic efficacy.
Multifocal Primary Central Nervous System (CNS) Diffuse Large B-Cell Lymphoma (DLBCL) in a Patient with Aquired Immunodeficiency Syndrome (AIDS)
Authors: Khokhar H , Wang K , Luis D
Published: October 2021

Introduction/Objective

Primary CNS DLBCL is a rare entity, with an incidence of less than 0.47 per 100,000, however, in immunocompromised patients, especially those with Human Immunodeficiency Virus (HIV-1) infection, the incidence increases dramatically to 2-6 percent. Here we present a case of multifocal DLBCL in a young 28-year-old homeless male with untreated AIDS and polysubstance abuse.

Methods/Case Report

He presented to the hospital with altered state of consciousness; a Computerized Tomography (CT) scan showed three ring-enhancing masses; one in the left fronto-temporal region, the largest in the left basal ganglia and the third in the cerebellum. The main lesion was biopsied and diagnosed as DLBCL. The patient developed aspiration pneumonia and demised from respiratory failure

Results (if a Case Study enter NA)

NA

Conclusion

Coronal sections of the brain revealed a large grey-tan, soft lesion of poorly defined, irregular borders located in the left basal ganglia that measured 5 x 4 x 4 cm, extended dorsally and laterally. A similar lesion was observed in the deep left cerebral hemisphere, affecting the temporal lobe and extending rostrally into the frontal lobe, but completely separate from the tumor in the basal ganglia. A third, much smaller lesion was found in the right cerebellar hemisphere. Histologically, the tumor was composed of sheets of atypical lymphoid cells with increased nuclear to cytoplasmic ratio, increased mitotic activity, and showed scattered areas of necrosis. In the peripheral areas, tumor cells were located in the Virchow Robin space, and in more central areas they have broken into the brain parenchyma. Tumor cells were positive for CD20 and CD79a, indicating their B-cell origin. Other markers positive by immunohistochemistry were PAX5, MUM1 and BCL6 and the Epstein-Barr Virus (EBV) latent membrane protein (LMP). Fluorescence In situ hybridization (FISH) corroborated the presence of Eptein-Barr encoded RNAs.
Report of Two Cases of ALK-Positive Histiocytosis in Young Children with Localized Lesions
Authors: Coffman B B , Dubyk F C , Chabot-Richards D , Rollins-Raval M A , Foucar K K , Babu D
Published: October 2021

Introduction/Objective

ALK-positive histiocytosis is a recently described entity which occurs in both children and adults and can present with localized or disseminated disease. Limited case reports and series describe histiocytic infiltrates with irregular morphologic features and typical immunoreactivity for CD68, CD163, lysozyme, S100(variable), CD4, and cytoplasmic ALK. ALK rearrangements are often confirmed by FISH or molecular sequencing. The presence of such rearrangements may make ALK inhibitor therapy possible, although further investigation is necessary. We report two cases of ALK-positive histiocytosis diagnosed at our institution.

Methods/Case Report

Patient 1 is a 4-year-old girl with a prior history of high-risk neuroblastoma status-post resection, bone marrow transplant, radiation, and chemotherapy. An MRI performed due to neurologic symptoms revealed a left frontal-enhancing mass. With concern for metastatic neuroblastoma, a biopsy was performed, which showed brain parenchyma infiltrated by large atypical histiocytes with moderate eosinophilic cytoplasm and irregular folded nuclei. The histiocytes stained positive for CD68, lysozyme, Factor XIIIa, CD163, CD4, S100(variable), and cytoplasmic ALK. An ALK rearrangement was confirmed by FISH studies. The patient is reportedly doing well on therapy.

Patient 2 is a previously healthy 2-year-old boy with a midline palate lesion. An incisional biopsy revealed a submucosal infiltrate of small lymphocytes and enlarged atypical histiocytes with abundant eosinophilic cytoplasm and vesicular folded nuclei. Histiocytes stained positive for CD68, CD163, Factor XIIIa, lysozyme, S100(variable), CD4, and cytoplasmic ALK. Given presence of an ALK rearrangement detected by FISH, the patient was started on single agent crizotinib therapy and has responded with near complete resolution.

Results (if a Case Study enter NA)

NA

Conclusion

ALK-positive histiocytosis is a clinicopathologically distinct entity with predilection for young children and presence of ALK rearrangements which may be amenable to ALK inhibitors, such as crizonitib. We report two additional cases to contribute to the expanding spectrum of this rare and relatively new entity.
Clinicopathologic characteristics of myeloid neoplasms that harbor both a DDX41 germline and an acquired DDX41 genetic alteration
Authors: Reichard K , He R , Viswanatha D
Published: October 2021

Introduction/Objective

Myeloid neoplasms associated with DDX41 germline genetic alterations are becoming increasingly recognized as a unique subset of hematologic cancer predisposition syndromes. As such, we sought to review their clinicopathologic characteristics.

Methods/Case Report

We searched our next-generation sequencing database for cases with two DDX41 variants; one variant at heterozygous variant allele fraction (VAF) indicating known or putative germline status, and second variant at low VAF consistent with an acquired subclone. We reviewed the clinicopathologic features.

Results (if a Case Study enter NA)

We identified 18 cases - male:female ratio 2.6:1, average age at presentation, 69 years (range 57-89). The diagnoses included no diagnostic abnormality (3), MDS-MLD (1), MDS-EB1 (1), increased blasts only(5-19%) (7), and AML (6). All had anemia [average hemoglobin (10.2) (range 6.5-12.9 g/dL)], 17/18 with thrombocytopenia [average 87 (range 22-222 K)], 17/18 with neutropenia [average absolute neutrophil count (ANC) (819) (range 90-1800)] and 13/18 with macrocytosis [average (101.5) (range 83.7-114 fL)]. Bone marrow cellularity (corrected for increased blasts >20%) was predominantly hypocellular (11/19) followed by normocellular (5/19). 3/19 cases showed erythroid dysplasia; no cases demonstrated granulocytic dysplasia; 7/19 cases showed megakaryocytic dysplasia. Of non-AML cases, 8/12 cases showed increased blasts [average 10% (range 5-19%)]. Of 4 cases without an increase in blasts, 1 showed MDS, 2 no dysplasia [1 -ANC of 666 and preserved platelets (222); 2- thrombocytopenia with preserved ANC (1800)] and 1 had slight megakaryocytic atypia. 16/17 cases were karyotypically normal. 14/18 of the patients are alive (median follow-up, 48) (8-125 months).

Conclusion

This cohort finds that myeloid neoplasms arising from DDX41 germline predisposition syndrome tend to present in older individuals, have infrequent dysplasia and are associated with a prolonged clinical course despite elevated blast counts at diagnosis. Recognition of these disorders is challenging and DDX41 testing should be included as part of genetic profiling. The presence of a suspected DDX41 germline variant may prompt confirmatory and familial testing, particularly in the event a hematopoietic transplant is a treatment option.
A rare case of post COVID-19 hemophagocytic lymphohistiocytosis in a pediatric patient
Authors: Rjoop A , Barukba M , Al Rusan O
Published: October 2021

Introduction/Objective

Hemophagocytic Syndromes are a cluster of disorders related to cytotoxic dysfunction of T/NK-cells and are mainly subdivided into Primary (familial) and Secondary (acquired) forms, with the latter usually linked to patients with viral infections; including EBV, CMV among many others. A myriad of other causes have been associated with hemophagocytic lymphohistiocytosis (HLH), most notably systemic inflammatory conditions; especially Juvenile Rheumatoid Arthritis and hematolymphoid malignancies particularly T/NK-cell lymphomas.

Methods/Case Report

A previously healthy 7-year-old boy, presented to the ER with fever and a skin rash over both lower limbs of 1 week duration. Two weeks prior he was tested for COVID-19 and was found to be positive. Physical examination further revealed slightly palpable liver and spleen. CBC was done and exhibited pancytopenia, further testing showed elevated LDH, hyperferritinemia and hypertriglyceridemia. However, serological testing for rheumatological conditions was unremarkable. Imaging studies were done and were noncontributory. Subsequently, a bone marrow aspirate and biopsy were done. The bone marrow aspirate showed afew histiocytes engulfing red blood cells and nuclear debris (hemophagocytic cells), complete trilineage maturation and normal M:E ratio of 3:1. Trephine biopsy was hypocellular for age and estimated at about 70%, composed of myeloid and erythroid precursors with various degrees of maturation. Megakaryocytes were adequate in number and showed normal morphology. Extensive histiocytic infiltration as highlighted by CD68 immunostain and focal phagocytosis were identified. CD34 highlighted <5% blasts, PAS special stain showed no fungal elements and no fibrosis was evident by Reticulin special stain. The background was devoid of lymphoid aggregates or granulomas. Stainable iron stores were depleted. No sideroblasts were identified. The patient was treated with corticosteroid and showed marked improvement and was discharged after 3 days.

Results (if a Case Study enter NA)

NA

Conclusion

Hemophagocytic lymphohistiocytosis can be a critical sequela of COVID-19 infection. Suggested mechanisms include impaired/delayed T-cell response and elevated levels of several inflammatory cytokines. Clinical suspesion is important in the diagnosis of these cases. Further study of this correlation is needed as we explore clinical sequelae of COVID-19 infection.
Bone marrow involvement by ATTR amyloid is common in cardiac amyloidosis patients and may signal advanced-stage disease
Authors: Dasari S , Chiu A , Theis J , Vrana J A , Kurtin P J , Rech K L , Dao L N , Howard M T , McPhail E D , Dispenzieri A , Grogan M
Published: October 2021

Introduction/Objective

Amyloidosis encompasses a heterogeneous group of disorders characterized by abnormal deposition of misfolded proteins leading to progressive organ failure. Accurate amyloid typing is essential for proper patient management, as treatment regimens vary dramatically across different types. Bone marrow (BM) biopsy, in conjunction with fat pad aspiration/biopsy, is often the first step in patients with suspected amyloidosis. Although BM involvement by AL amyloid has been previously characterized, little is known about the incidence, morphology and clinical phenotype of non-AL amyloid in BM.

Methods/Case Report

We retrospectively identified 1469 BM biopsies by querying our reference laboratory database of 19,298 specimens from myriad anatomic sites typed by mass spectrometry-based proteomics (LC-MS/MS). These were reviewed for frequency of amyloid types (N=1469), distribution of amyloid deposits (N=139), and clinical phenotypes (N=345), with particular emphases on cardiac involvement.

Results (if a Case Study enter NA)

We identified the following amyloid types: AL (N=1172; 79.8%), ATTR (transthyretin) (N=240; 16.3%), AH (immunoglobulin heavy chain) (N=38; 2.6%), AA (serum amyloid A) (N=17; 1.2%), and Aβ2M (β2-microglobulin) (N=2; 0.1%). ATTR deposits showed striking predilection for periosteal soft tissue and/or periosteal vessels, and rarely involved BM stroma and/or interstitial vessels, while AL variably involved these compartments. AA primarily involved interstitial vessels. Both AL and ATTR cases commonly had a monoclonal gammopathy (AL: 92.9%; ATTR: 62.5%) with concomitant cardiac amyloidosis (AL: 91.6%; ATTR: 100%). Compared to AL, ATTR patients had higher stage cardiac amyloidosis and lower overall survival.

Conclusion

ATTR is common in BM, constituting16.3% of cases in our cohort. Rarer amyloid types, such as AA, AH and AB2M can also occur in BM. ATTR was frequently identified in patients with concomitant monoclonal gammopathy, in whom AL may have been suspected. Although ATTR deposits have distinctive morphologic distribution, primarily involving periosteal soft tissue and/or periosteal vessels and rarely involving BM stroma and/or interstitial vessels, there is considerable morphologic overlap with AL. Therefore, it is imperative to type BM amyloidosis, preferably by LC-MS/MS, to ensure proper patient management. Furthermore, BM involvement by ATTR may be a marker for advanced stage of disease.
Four PAX5 Negative Nodular Sclerosing Hodgkins Lymphoma Case Series
Authors: Dabrowski D S , Afude J , Wei E
Published: October 2021

Introduction/Objective

Hodgkins lymphoma is a B cell lymphoproliferative disease, with most cases showing PAX5 positivity. Very few PAX5 negative hodgkins lymphoma cases have been described. We describe four PAX5 negative nodular sclerosing hodgkins lymphoma cases. All received standard chemotherapy, three received additional chemotherapeutic agents. Exploring these rare cases can be invaluable in characterizing and later treating his atypical presentation.

Methods/Case Report

Four cases of Hodgkins Lymphoma were diagnosed between 2017 and 2020. Two males and two females between 31 and 80 year old. Case 1 was a 31 year old male with a left neck lymphadenopathy that revealed nodular sclerosing Hodgkins lymphoma without bone marrow involvement. IHC staining revealed CD15, CD30, fascin and MUM-1 positivity, and PAX5 negativity. He received Doxorubicin, Vinblastine, Dacarbazine (AVD) and Brentuximab with radiation, and later brentuximab with bendamutine. Follow up PET-CT and left axillary node excisional biopsy found nodular sclerosing classic hodgkins. He received Ifosfamide, Carboplatin, and Etoposide.

Case 2 was a 37 year old male with bilateral mediastinal lymphadenopathy that demonstrated nodular sclerosing Hodgkins lymphoma on biopsy. The cells were CD15, CD30 positive, and PAX5 negative. He received AVD with bleomycin (ABVD), and field radiation with excellent response and is currently under surveillance. Case 3 was a 31 year old female with a left chest mass that demonstrated nodular sclerosing Hodgkins lymphoma. The cells were positive for MUM1, CD30 and fascin and negatively for CD15 and PAX5. She received ABVD. Case 4 was an 80 year old female with prior stage IV gastric diffuse large B cell lymphoma treated with Rituximab, Cyclophophamide, Vincristine, and Prednisone and achieved remission. She later developed neck masses that were biopsied revealing classic Hodgkins lymphoma. The cells stained for CD30, for CD15, and were negative for PAX5. She was started on AVD and is on palliative care.

Results (if a Case Study enter NA)

NA

Conclusion

Most hodgkins lymphomas are PAX5 positive. We found four cases of PAX5 negative Hodgkins lymphoma. Incidentally, all were of the nodular sclerosing subtype. All cases were treated with recommended chemotherapy and/or radiation. All four cases had good response with reduction in disease burden. This finding suggests that PAX5 negativity still allows the nodular sclerosing hodgkins lymphoma to be responsive to standard treatment modalties.
Colony-stimulating factor 3 receptor gene (CSF3R) T618I mutated chronic myelomonocytic leukemia: A proliferative subtype with a distinct mutational profile
Authors: Kwon A , Ibrahim I , Le T , Jaso J , Weinberg O , Fuda F , Chen W
Published: October 2021

Introduction/Objective

Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm characterized by sustained monocytosis, ranging from cytopenia with a dysplastic subtype to leukocytosis with a proliferative subtype, with a typical mutational profile involving TET2, ASXL1, and SRSF2. Mutation in colony-stimulating factor 3 receptor gene (CSF3R) is commonly associated with chronic neutrophilic leukemia (CNL) but exceedingly rare in CMML, particularly CSF3R T618I (~10 cases described, ~30 cases of CSF3R non-T618I mutations). We report a case of CSF3R T618I mutated CMML and compare the clinicopathologic features to reported CMML cases with and without CSF3R T618I mutations.

Methods/Case Report

A 27-year-old woman presented for evaluation of leukocytosis, sustained monocytosis, and anemia. Peripheral blood (PB) revealed leukocytosis (white cell count 35x109/L), left-shifted and dysplastic neutrophils (myelocytes and metamyelocytes, 5%), absolute and relative monocytosis (7x109/L, 29%), anemia (Hgb 4.3 g/dL), and thrombocytopenia. Bone marrow aspirate and core biopsy demonstrated a hypercellular marrow with increased myeloblasts (~3%, immunophenotypically aberrant by flow cytometry), increased myelomonocytic cells, and multilineage dysplasia, including ring sideroblasts and hypolobated megakaryocytes. Cytogenetic and molecular studies revealed a normal karyotype and mutations in CSF3R T618I, ASXL1, SETBP1, BCORL1, KRAS, and PTPN11. Despite the presence of a CSF3R T618I mutation, CMML was diagnosed given marked monocytosis, left- shifted neutrophils in PB, multilineage dysplasia, and immunophenotypically aberrant myeloblasts.

Results (if a Case Study enter NA)

NA

Conclusion

Our case demonstrates clinicopathological features similar to those of reported CSF3R T618I mutated CMML, i.e., a proliferative subtype and less likely to have co-occurring mutations in TET2 or SRSF2, which is distinct from CSF3R non-T618I mutated CMML; the latter often has a dysplastic subtype and mutational profile of frequent TET2 and SRSF2 mutations, similar to CSF3R unmutated CMML. While additional cases with this unusual mutation need to be studied to arrive at a more definitive conclusion, the CSF3R T618I mutation seems to define a unique proliferative subtype CMML with a distinct mutational profile.
Therapy-Related Mixed Phenotype Acute Leukemia: Report of two cases with clinicopathological and molecular data
Authors: Anelo O M , Alnooor F , King L C , Murray G
Published: October 2021

Introduction/Objective

Therapy-related mixed phenotype acute leukemia (Tr-MPAL) is a rare and aggressive disease comprising blast cells of more than one hematopoietic cell lineage. There is limited patient outcome data with this diagnosis. Hence, we present two such cases with clinicopathologic correlation.

Methods/Case Report

Clinical and pathology data were obtained from institutional electronic health records for two cases of Tr-MPAL identified in the past three years (2018-2020).

Results (if a Case Study enter NA)

Case 1: 60-years old female, history of chemo-radiotherapy for breast carcinoma, had 49% circulating dimorphic blasts. By immunophenotype, blasts were positive for CD34, CD117, HLA-DR, cCD3, TdT, CD13, CD15, CD38, CD2, CD7, and MPO by cytochemistry, negative for B-cell lineage markers, consistent with Tr-MPAL, T/Myeloid. Ancillary studies revealed normal female karyotype, FLT3-ITD positivity, and DNMT3A frameshift mutation. The patient achieved remission with ALL regimen Hyper-CVAD/methotrexate-cytarabine and underwent an allogeneic stem cell transplant (SCT). The patient was disease-free and on maintenance therapy post 2 years of initial diagnosis.

Case 2: 49-years old female, history of chemotherapy for breast carcinoma, had 77% circulating dimorphic blasts (MPO+/PAX5- and MPO-/PAX5+/CD79a+). By immunophenotype, blasts were positive for CD34, CD117, HLA-DR, CD13, CD33, CD15, CD11b, CD19+(dim), cytoCD79a(subset), MPO(subset) and negative for CD14, CD10, CD7, CD8, cCD3, cCD22, and TdT, consistent with Tr-MPAL, B/Myeloid. Ancillary studies revealed normal female karyotype, FLT3-ITD positivity, mutations in RUNX1(frameshift insertion S318fs), SETD2(frameshift insertion P1403fs), WT1(frameshift deletion T377fs), ATM (LI555H), CREBBP (P84S), and DNMT3A (W305). The patient was treated with ALL regimen Hyper-CVAD/methotrexate-cytarabine but relapsed in the post-induction phase with a similar genetics profile. Once remission was achieved, the patient underwent allogeneic SCT and is disease-free while on maintenance therapy post 18 months of initial diagnosis.

Conclusion

Phenotypically different Tr-MPAL also differ by their underlying genetic abnormalities and may vary in response to therapy. A large cohort of cases may provide us further insights into the genetics and survival outcome of this therapy-related leukemia subtype.
Outcome of patients with concurrent chronic lymphocytic leukemia and Hodgkin lymphoma
Authors: Deb P Q , Jiang J , Bhattacharyya P K
Published: October 2021

Introduction/Objective

Concurrent diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and Hodgkin lymphoma (HL) is rare. CLL/SLL can rarely advance into Hodgkin-variant of Richter transformation, or there can be a simultaneous presence of separate CLL/SLL and HL from different clonal origins. Due to its rarity, the epidemiological features and outcome of concurrent CLL and HL are not well-known. Here we have used the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database to identify concurrent CLL/SLL and HL cases and analyzed overall and disease-specific survival across various epidemiological factors.

Methods/Case Report

We identified all patients diagnosed with CLL/SLL and HL between the period of 1975 to 2017. Next, we identified the patients with a simultaneous CLL/SLL and HL diagnosis by matching the patient identification number. Overall survival and disease-specific survival were calculated using Kaplan-Meier curves and Cox proportional hazards models.

Results (if a Case Study enter NA)

We identified 166 cases with a concurrent diagnosis of CLL, and HL. 4 cases were excluded from analysis as the diagnosis of CLL and HL were not simultaneous. The age distribution of the patient showed a unimodal distribution, with most patients being diagnosed between the age of 50 and 79. 67% of patients were male, and 92% of patients were Caucasian. The majority of the CLL was diagnosed in bone marrow or lymph nodes, while almost all HL were diagnosed in lymph nodes. Both disease-specific and overall survival were worse for patients with the advanced age of diagnosis. Race or sex did not significantly affect patients’ survival.

Conclusion

Our comprehensive review of clinical and epidemiological features of concurrent CLL and HL cases shows that the age of diagnosis is the most significant factor in determining the survival of these patients.
Clonally-Related Composite Classic Hodgkin Lymphoma and Follicular Lymphoma
Authors: Larson D P , Ketterling R P , He R , Shi M , McPhail E D , Yuan J
Published: October 2021

Introduction/Objective

Composite classic Hodgkin lymphoma and follicular lymphoma (CHLFL), defined as CHL and FL occurring simultaneously at the same site, is rare and poorly understood. While both Hodgkin/Reed-Sternberg (HRS) cells and FL are thought to be derived from germinal center B-cells, the relationship between CHL and FL when coexistent is unclear. Here, we present two cases of CHLFL and show that the CHL and FL components have a clonal relationship by FISH.

Methods/Case Report

Case #1 is a 50-year-old man with abdominal and mediastinal lymphadenopathy. An excised mesenteric lymph node showed two distinct components diagnostic for FL, grade 1-2 and CHL. Case #2 is a 63-year- old woman with a history of FL with transformation to diffuse large B-cell lymphoma. Cytogenetic studies showed a complex karyotype with an add(9p), del(10q), and trisomy 16. Post-treatment imaging revealed left axillary adenopathy. An excised axillary lymph node showed CHL with peripheral areas of FL, grade 3A.

Both cases had areas of typical FL with BCL2-positive phenotype and no significant CD30/CD15 expression. HRS cells were CD45/CD20-negative, expressed CD30 (strong), CD15, and PAX5, and were present in a mixed inflammatory background. No EBV RNA was present by in situ hybridization. Interestingly, HRS cells in case #1 expressed both BCL6 and BCL2.

FISH was performed in both cases. Case #1 had a BCL2 rearrangement in 48% of FL nuclei and in 100% of HRS cells. In case #2, targeted probes were used based on prior cytogenetic results. Here, 47% of FL nuclei and 44% of HRS cells had a 16p duplication; additionally, 32% of HRS cells had an unbalanced IGH rearrangement with loss of the IGH variable region, suggesting possible clonal evolution. No rearrangement of BCL2 or BCL6 was present.

An additional 27 CHLFL cases from the literature were reviewed. CHLFL was mostly nodal and occurred in late adulthood in patients with or without a history of FL. It presented at advanced clinical stage, with a 5-year overall survival of 22%. BCL2 expression in HRS cells was common. Bone marrow involvement was 45% (5/11) and consisted of FL exclusively. Five of six tested cases demonstrated BCL2/IGH rearrangement in both FL and HRS cells.

Results (if a Case Study enter NA)

NA

Conclusion

Composite CHL and FL are often clonally related and may share a common progenitor B-cell origin – likely a germinal center B-cell – from which additional genetic abnormalities are acquired to develop two distinct lymphomas.
Knowledge is Power: Pathology Activity Booths in Community Health Fairs
Authors: Ojukwu K , Miranda-Taylor M , Tran T , Ji P
Published: October 2021

Introduction/Objective

Our pilot project “Pathology Activity Booths” is an innovative approach to investigating whether pathology activity exhibits at health fairs could increase access and promote learning and understanding of health topics and pathology of diseases. Health fairs are an effective form of community-based health promotion conducted in many underserved communities.

Methods/Case Report

Booth #1 (Colorectal Cancer Awareness Fair): Microscopes with histology slides of colon biopsies, with enlarged corresponding colonoscopy images, were displayed showing the histology of normal colon, abnormal colon and cancer (colon adenocarcinoma).

Booth #2 (Children’s Back-To-School Fair): Microscopes with histology slides of normal skin, lung, kidney, liver, intestine, and brain tissue were shown.

Post participation surveys assessed whether participants knew anyone with the diseases presented, had previous experience with microscopes, and/or felt they understood and learned from their experience at the booth.

Results (if a Case Study enter NA)

There were 71 total participants. At Booth #1, 100% (42/42) of participants stated they understood what they saw under the microscope and 95% (40/42) felt they learned something new. At Booth #2, 86% (25/29) of participants stated they understood what they saw under the microscope and 76% (22/29) stated they learned something new. One participant exclaimed she would now make her husband get the colonoscopy he had been avoiding.

Conclusion

The overwhelmingly positive responses indicate that pathology booths could be promising in promoting health knowledge in our patient population. Greater understanding of health topics may lead to increased use of screening tests that can ultimately improve health outcomes. Pathologists are well suited to be direct resources of accurate information for patients. As physicians who closely evaluate human disease, we can effectively provide access to a new, different and engaging perspective to community health education. Pathology activity booths may be a valuable resource for patients, an innovative method of teaching the community and a creative tool to enhance trainees’ experience and teaching ability.
Large-scale human tissue analysis identifies Uroplakin 1b as a putative diagnostic marker in surgical pathology
Authors: Reiswich V , Dum D
Published: October 2021

Introduction/Objective

Uroplakin 1B (Upk1b) protein is relevant for stabilizing and strengthening epithelial cells that line the bladder. It helps to prevent urothelial cells from rupturing during bladder distension. Based on RNA expression studies Upk1b is expressed in a limited number of normal tissues.

Methods/Case Report

To comprehensively evaluate the potential diagnostic and prognostic utility of Upk1b expression analysis, a tissue microarray containing 15,182 samples from 127 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry.

Results (if a Case Study enter NA)

Upk1b positivity was found in 61 (48%) different tumor types including 50 (39%) with at least one moderately positive and 39 tumor types (31%) with at least one strongly positive tumor. The highest positivity rate and the highest levels of expression was found in urothelial neoplasms (58-95%), Brenner tumors of the ovary (92%), epitheloid mesothelioma (87%), serous carcinomas of the ovary (58%) and the endometrium (53%) as well as squamous cell carcinomas of various sites of origin. Immunostaining was infrequent in lung adenocarcinoma (0%) and largely absent in colorectal (0.7%) or prostatic adenocarcinoma (1.3%). In urothelial tumors cancer, low Upk1b expression was linked to high grade and invasive tumor growth (p<0.0001 each) as well as nodal metastasis (p=0.0006) but an unequivocal link to unfavorable tumor features was lacking in various other tumor entities.

Conclusion

In conclusion, the differential Upk1b expression in different tumor entities suggests potential diagnostic applications of Upk1b immunohistochemistry in panels for the distinction of malignant mesothelioma from adenocarcinoma of the lung, urothelial carcinoma from prostatic adenocarcinoma in the bladder, or pancreatico-biliary and gastro-esophageal from colorectal adenocarcinomas.
A case of TFE-3-positive non-neoplastic pseudodecidualized endometrium presenting as a cervical mass
Authors: Serinelli S , de la Roza G , Zaccarini D J
Published: October 2021

Introduction/Objective

TFE-3 gene encodes a transcription factor that promotes the expression of genes involved in cell growth and proliferation. Its overactivation can result in oncogenic activity. Although TFE-3 seems to be almost universally expressed in normal tissues, this expression should be at very low levels and strong nuclear expression of TFE-3 is seen almost exclusively in tumors containing or lacking the TFE-3 gene fusion. These include renal cell carcinoma, alveolar soft part sarcomas, epithelioid hemangioendotheliomas, PEComas, granular cell tumour, solid pseudopapillary neoplasm of the pancreas, and ovarian sclerosing stromal tumors. It must be emphasized that only nuclear expression of TFE-3 is of diagnostic value, as non-specific cytoplasmic staining is common.

Methods/Case Report

A 30-year-old woman with pelvic pain, heavy vaginal bleeding and ureteral stricture on oral contraceptive pill was found to have a cervical mass on exam. Cervical biopsy showed fragments of benign squamous epithelium and polypoid endometrial tissue with atrophic glandular component, stromal pseudodecidualization and abundant mixed inflammation. The stroma was positive for CD10, and negative for P16, desmin, cytokeratin ae1/ae3, CD34, calretinin. There was patchy moderate to strong nuclear staining for TFE-3 (Anti-TFE-3 rabbit monoclonal primary antibody, Cell MarqueTM). No evidence of a neoplastic process was seen, and the overall findings fit with either prolapsed endometrial tissue or endometriosis. TFE-3 by FISH showed no rearrangement of the TFE-3 gene region, ruling out alveolar soft part sarcoma.

Results (if a Case Study enter NA)

NA

Conclusion

The Human Protein Atlas, a program mapping all the human proteins in cells and tissues, shows that endometrial stromal and glandular cells can have moderate TFE-3 nuclear expression, using Anti-TFE-3 rabbit polyclonal antibody (Prestige Antibodies ®). In our case, focal strong expression was seen using a monoclonal antibody. In the pathology literature this finding has not been previously reported. Pathologists should be aware of the possibility of strong nuclear expression of TFE-3 in non-neoplastic endometrium to avoid potential misdiagnosis.
Transforming Healthcare Means Zero Harm: Laboratory Testing Matters
Authors: Mina A
Published: October 2021

Introduction/Objective

My role model when I was a medical technologist intern was a chief pathologist who taught me to speak up when something is unsafe and to serve willingly, do what is right, be fair and excellent in work. His character impacted my whole life and career. Every moment matters; life is precious and something to protect. The patient and their care teams depend upon accurate, safe and high-quality clinical laboratory tests result to achieve positive patient outcomes.

Methods/Case Report

Clinical Practice

Results (if a Case Study enter NA)

We can do better. Everybody can be surveyors with greater understanding of pathophysiologic processes in disease, extensive experience working in laboratories and in-depth knowledge about complaince, quality, mistake-proofing care, patient-focused and laboratory management.

Diagnostic testing would be the method to screen for disease, confirm disease, and monitor disease in hopes of secondary prevention - to identify latent disease to “catch it early.” The screening tests could be anything from newborn screening for inborn metabolism errors, adult screening tests (like mammograms, pap smears, and colonoscopies), to high-risk population screenings to detect HIV, RPR, and gonorrhea. The disease must have a high prevalence to justify the expense of therapy and should be detectable before symptoms arise. The test must not have many false positives but extremely high sensitivity. The results of these tests could lead to the three different methods of prevention.

Primary prevention would reduce the risk of developing cardiovascular disease or stroke. Secondary prevention would detect the disease early to prevent progression of the disease. Tertiary prevention would reduce disabilty and promotion of rehabilitation from the disease like strokes or rehab programs.

Conclusion

In conclusion, this information provides clinicians with a laboratory test menu guidelines to improve clinical practice. We can all learn well to focus on what really matters. Together, we can make healthcare better, more patient-centered, less costly, and safer.
Utilization of Short Tandem Repeat Analysis to Resolve Specimen Mislabeling in the Anatomic Pathology Laboratory
Authors: Tenney T , Robinson B , Sullivan H C
Published: October 2021

Introduction/Objective

A mislabeled specimen is an example of preanalytical error that can have significant consequences on patient care. These errors can be difficult to detect and resolve. One method to confirm genetic identity is short tandem repeat (STR) analysis, which is utilized in forensic investigations, paternity studies, and post- hematopoietic stem cell transplantation monitoring. Herein we present application of STR analysis to resolve a suspected specimen mislabeling prior to receipt in our anatomic pathology laboratory.

Methods/Case Report

DNA was extracted from paraffin embedded tissues. Chimerism testing was performed by STR analysis using the Globalfiler (ThermoFisher Scientific) and analyzed by Chimermarker (Softgenetics) automated chimerism software.

Results (if a Case Study enter NA)

Colon biopsies were received for a single patient (#1) with two requisition forms. Each specimen (A-F) was labeled with the patient’s name, with specimens A-D noted on first page of requisition and specimens E-F on the second requisition page. After the case was signed out, the lab was contacted looking for biopsy results on another patient (#2) who was seen on the same day as patient #1. Review of all the patients seen in the endoscopy suite on the given date raised suspicion that specimens E-F from the second page of the requisition actually pertained to patient #2. STR analysis performed on specimens confirmed that specimens E-F were genetically distinct from those labelled A-D. Tissue from a subsequent biopsy on patient #2 was analyzed by STR testing, which was identical to STR results performed on specimens E-F.

Conclusion

Here we utilized STR testing to resolve a suspected mislabeled specimen, allowing the appropriate diagnosis to be attributed to the correct patient. This is a unique application of a common method, which could be implemented in anatomic pathology laboratories to resolve cases of specimen mix-ups.
Ensuring Standardization, Quality Management And Improvement Of Point-Of-Care Testing In The Municipal Public Health System Based Ambulatory Care And School Health Clinics In New York City
Authors: Sherpa T , Choesang T , Ahmad S , Huq Ronny F M
Published: October 2021

Introduction/Objective

Operated under different acute care hospital clinical laboratory limited-service laboratory (LSL) licenses, our New York City five borough spanning multisite ambulatory clinics and school-based clinics have been offering various waived point-of-care tests (POCTs) and provider-performed microscopy (PPM) to the local communities. A wide range of variability existed among the clinics concerning regulatory compliance, test performance, quality control and training. To ensure standardization and quality of POCT across the health system, our laboratory service adopted and implemented a plan for systemwide LSL transfer from the acute care hospitals to ambulatory care laboratory service for centralized implementation, monitoring, and oversight of the POCT operations.

Methods/Case Report

Having over 60 clinics, while transferring the LSLs, we chose multi-site license with ten or more sites on each license and by phase transfer from NYSDOH. Since the commencement of the transfer, system wide our qualified laboratory personnel have been updating and providing standard operating procedures (SOP), performing quality assurance and validation of new tests/devices, providing competency assessments and helping clinical staffs maintain compliance with state and other regulatory agencies.

Results (if a Case Study enter NA)

After the final phase of the transfer and POCT standardization implementation in 63 clinics, currently the clinical staffs performing POCT, get expeditious training and troubleshooting in more timely manner and the providers get the results of the ordered POCTs much faster and more efficiently and overall the quality metrics get improved markedly, indicated by internal audit team.

Conclusion

Even though Implementation of the planned POCT standardization was initially challenging due to the vastness and complexity of our multisite ambulatory care network and later confounded by the COVID -19 pandemic effect but eventually, it helped improve patient care delivery significantly and very effectively. Expectedly, our planned transfer implementation provided standardization and ensured improved quality of POC testing across our health system.
Challenges of Conducting Point-Of-Care Testing Operations During The COVID-19 Pandemic In The Municipal Public Health System Based Ambulatory Care And School Health Clinics In New York City
Authors: Sherpa T , Choesang T , Ahmad S , Huq Ronny F M
Published: October 2021

Introduction/Objective

Our New York City Municipal Public Health System based multisite ambulatory clinics and school-based clinics, offer various waived POCT (point of care tests) and provider performed microscopy (PPM). To ensure standardization and quality of POC testing across our health system, our laboratory service conducts system wide centralized implementation, monitoring and oversight of the POCT operations in regard to regulatory compliance, test performance, quality control and training. With the emergence of the COVID-19 infection in the New York City, like all other clinical laboratories, our ambulatory care clinics encountered numerous hurdles and challenges. Here we elaborated the issues that we encountered and how we managed to overcome during the COVID-19 Pandemic.

Methods/Case Report

We categorized the challenges that affected our managers as well as field level laboratory operations and have devised a plane to deal with COVID-19 related predicaments.

Results (if a Case Study enter NA)

Among the staffing issues, staff relocation to the acute care hospital laboratories during the peak of the pandemic caused massive delay or cessation of POCT operations in our ambulatory care clinics. Manual result entry, for COVID-19 testing, at the patient portals due to lack of interface with the reference testing labs, staff shortages and frequent absences due to illness and fatigue were primary issues noted at technical level. Furthermore, there were notable delays in the processing of paper works and new staff recruitments. The lack of and significant delays in the critical laboratory supplies was another major management issue.

Conclusion

Given the vastness and complexity of our multisite ambulatory care network, the COVID -19 pandemic impacted our ambulatory care clinic POCT operation in a very challenging way. However, our timeliness, coordinated interventions, close communications and initiatives handled the obstacles that arose very effectively to the ensure quality of POC testing, patient safety and quality care across our health system.
Utilization of 2D Barcode Technology to Create Surgical Pathology Reports
Authors: Qu Z , Qu E , Huang J , Micale M A , Li E
Published: October 2021

Introduction/Objective

After professional transcription service is eliminated, pathologists inevitably undertake the task of diagnostic data entry into pathology repot by adapting a variety of methods such as speech recognition, manual typing, and pre-texted command. Errors and inefficiency in reporting remain common problems, especially for information with unusual syntax such as genotype or nucleotide sequences. To overcome these shortcomings, we introduce here a novel application of a well-established technology as a complementary method, namely 2- dimensional (2D) barcode symbology.

Methods/Case Report

Commonly used diagnostic wordings of pathology reports including specimen type, surgical procedure, diagnosis, and test results are collated and organized by organ (specimen type) and by their frequency of usage/occurrence. Next, 2D data matrix barcodes are created for these diagnostic wordings using a on-line tool (www.free-barcode-generator.net/datamatrix/). The 2D barcodes along with their text are displayed on the computer screen (or printed out as a booklet). A 2D barcode scanner (Symbol LS2208, Motorola) was used to retrieve the text information from the barcodes and transfer into the pathology report. To assess the efficacy of this barcode method, we evaluated the time of data entry into reports for 117 routine cases using an on-line stopwatch and compared with those by other data entry methods.

Results (if a Case Study enter NA)

Unlike manual typing or speech recognition, the barcode method did not introduce typographic or phonosemantic errors since the method simply transferred pre-texted and proof-read text content to report. It was also faster than manual typing or speech recognition, and its speed was comparable to that of the pre-text method integrated in LIS but did not require human memorization of innumerable text commands to retrieve desired diagnosis wordings.

Conclusion

Our preliminary results demonstrated that the diagnostic data entry time was reduced from 28.5% by other methods to 22.1% by the barcode method although due to the small sample size, statistical analysis was not conclusive.
Laboratory Testing Patterns by Day of Hospital Stay for Medical and Surgical Hospitalizations
Authors: Brimhall B , Whitted M , Windham A , Fernandez J
Published: October 2021

Introduction/Objective

Studies of laboratory test utilization and costs by specific hospital day of stay (DOS) have yet to be widely published. Evaluation of laboratory test use by DOS would be helpful to better predict laboratory test reduction as hospital length of stay (LOS) is shortened, since testing on the final day of hospitalization is likely to differ from the average daily figures.

Methods/Case Report

Using an internal cost accounting database, we evaluated laboratory tests and costs by hospital DOS over one year (2017) at a large health system (N=133,139 hospital days). To evaluate changes over the first days of hospitalization, we set day 1 of hospitalization as a baseline and determined subsequent days as a percentage of day 1 figures. We also calculated laboratory variable cost as a percent of aggregate variable costs per DOS. We limited our analysis to the first week of hospitalization. We employed Medicare Severity Diagnosis Related Groups (MSDRG), used by the US Centers for Medicare and Medicaid Services (CMS), to aggregate hospital encounters into medical or surgical hospitalizations using MSDRG grouping methods.

Results (if a Case Study enter NA)

For medical inpatient stays, average laboratory tests (variable costs) were 10.8 ($74.11) on day 1, 7.7 ($38.53) on day 2, and 5.8 ($23.75) on day 3, with little change over the next four hospital DOS. Laboratory testing, as a percent of day 1 testing, for days 2-7 was: 70.7%, 53.4%, 54.3%, 54.5%, 55.1%, and 54.0%. Laboratory variable costs represented 7.8% of aggregate variable costs on hospital day 1 and declined sequentially over days 2-7: 5.6%, 4.3%, 3.9%, 3.8%, 3.8%, and 3.5%. For surgical hospitalizations, average laboratory tests (variable costs) were 18.2 ($130.02) on day 1, 11.9 ($57.38) on day 2, and 8.4 ($35.32) on day 3. As with medical stays, there was little change over the next four hospital DOS. Laboratory testing, as a percent of day 1 testing, for days 2-7 was: 65.6%, 46.1%, 44.6%, 46.3%, 45.9%, and 44.9%. Laboratory variable costs represented 3.2% of aggregate variable costs on hospital day 1 and remained essentially unchanged over the following days (range 3.3%-3.7%).

Conclusion

Laboratory variable costs are highest on the first day of hospitalization and decline over subsequent days to flatten by day 3.