bluuebunny/crossref_metadata_2025 huggingface dataset:
Review of Sclerosing stromal tumor: A relatively rare ovarian neoplasm
Authors: Fathima S , Mansheim K
Published: November 2022

Introduction/Objective

Sclerosing stromal tumor (SST) is sex cord stromal tumor which is rare primary ovarian neoplasm. Because its clinical presentation and imaging findings accurate preoperative clinical diagnosis can be difficult. We report three cases of a sclerosing stromal tumor of ovary and histopathological presentation.

Methods/Case Report

Our patients had an age ranged from 27-40 years with primary ovarian neoplasm and as incidental in 64-year-old patient. Radiologically lobulated and heterogeneously enhancing, partially calcified masses with nodular rind of avid enhancement about the periphery of the lesion with high risk malignancy were seen. Grossly the masses had firm tan-white, solid, lobulated cut surfaces with patchy calcifications

Results (if a Case Study enter NA)

Microscopically all the three tumors showed a hyalinized, well-circumscribed nodule with few scattered trabeculae of spindled to plump cells with pale grey cytoplasm within a sclerotic stroma with few staghorn- like blood vessels around the periphery. Scattered calcifications were identified. No mitoses are identified. The reticulin stain showed pericellular focal nested staining pattern. There was no necrosis, pleomorphism, or features of malignancy were identified. Findings were consistent with a sclerosing stromal tumor.

Conclusion

Ovarian sex cord-stromal tumors are relatively infrequent neoplasms of all primary ovarian tumors. Clinical and sonographic findings alone do not predict the presence of this tumor. SSTs should be considered in differentials in young females with unilateral masses with cystic and solid masses. These tumors carry a good prognosis. Histopathological features along with immunohistochemsitry establish the diagnosis.
Diagnostic Dilemma of a Widely Metastatic Gastric-type Cervical Adenocarcinoma
Authors: Jaramillo C , Adams T , Shah S , Miller C , Teschan N
Published: November 2022

Introduction/Objective

Gastric-type cervical adenocarcinoma is an HPV-independent neoplasm accounting for 0.5-0.6% of cervical carcinomas, typically in women aged 50-55 years presenting with bleeding or watery vaginal discharge. The immunophenotypic and molecular overlap with mucinous pancreatic carcinomas presents a diagnostic dilemma in metastatic cases.

Methods/Case Report

We report the case of a 50 year-old female with a remote history of cervical dysplasia who presented with abdominal pain in December 2020 with CT notable for an incidental prominent, heterogeneous appearing cervix. Follow-up in February-August 2021 showed two unsatisfactory pap smears and an ultrasound of the cervix revealed Nabothian cysts. A friable cervix and vaginal discharge were noted on physical exam, however, no malignancy was identified on endometrial and endocervical biopsies. The patient re-presented in March 2022 with a persistent cough and was found to have a metastatic process of unknown origin involving bilateral ovaries/lungs, abdominal mesentery, pancreas, and pelvis. Lung, cervical, endometrial, and pancreatic sampling demonstrated well- differentiated mucinous adenocarcinoma with an immunophenotype positive for CK7 and MUC6 and negative for PAX-8, CDX-2, ER, Vimentin, TTF1/Napsin, GATA-3, CK20, and p16 with wildtype p53 staining compatible with endocervical, upper gastrointestinal, or pancreaticobiliary origin. Labs were notable for elevations in CA125 (198 U/mL) and CA19-9 (4,939 U/mL), further supporting pancreatic or gynecologic primaries. A retrospective review of all gynecologic cytology and histology specimens collected from the uterus and cervix in 2021 revealed similar bland mucinous epithelium, without overt atypia or features of malignancy. Next generation sequencing demonstrated a nonspecific and complex mutational burden including STK11 D23fs*25, SMAD4 N107fs*3, CDKN2A/B loss, KRAS G12V, and MTAP loss.

Results (if a Case Study enter NA)

NA

Conclusion

The treatment regimens for metastatic mucinous carcinoma from the cervix and pancreas differ significantly. Ultimately, the diagnosis of widely metastatic gastric type endocervical carcinoma was made possible through extensive clinical/radiographic and retrospective pathologic correlation with the incorporation of molecular studies.
Dissecting Diagnostic Discrepancies between Intraoperative and Permanent Head and Neck Pathology Sections at a Large University Medical Center
Authors: Gutierrez Alonso D , Paulo De Lima Guido L , Langlie J A , Velez-Torres J , Garcia-Buitrago M T , Gomez-Fernandez C
Published: November 2022

Introduction/Objective

Accurate correlation between intraoperative frozen section (FS) and subsequent permanent section (PS) diagnoses is essential for quality patient care. Intraoperative FS is used for confirmation of diagnoses and margin status (MS) evaluation in head and neck (H&N) pathology. Reported FS-PS discrepancy rates for H&N cases range between 1.42% to 1.80%, mostly due to sampling and interpretation errors. We sought to review our experience with FS and concordant PS from H&N pathology cases diagnosed at a high volume, university medical center.

Methods/Case Report

Correlation was performed between intraoperative FS and paraffin-embedded PS of H&N surgical resections between January 2019 to December 2021. FS-PS discrepancies were classified due to “sampling” or “interpretation”. Recurrence rates based on a 2 year follow up period of 2019 cases was also recorded.

Results (if a Case Study enter NA)

2337 H&N cases yielded 11108 intraoperative FS diagnoses. FS-PS correlation identified 142 (1.27%) discrepancies. Of these, 85 (60%) were for MS control, comprised of 45 (53%) due to “sampling” and 40 (47%) to “interpretation”. FS slides generally represented a single top section taken from the tissue, with “sampling” discrepancies due to discordant diagnoses identified on a deeper cut of tissue on the PS slides.

Common “interpretative” discrepancies included overlooking high-grade dysplasia. For patients diagnosed in 2019, we found that 6% of discrepant cases of locoregional disease over a 2 year follow up period were due to inadequate margin control.

Conclusion

Our institutional intraoperative FS-PS discrepancy rate for H&N pathology cases is 1.27%, and within the national quality standards. Our FS-PS discrepancy rate for H&N cases related to MS control were mostly due to “sampling". Intraoperative review of deeper cuts of FS tissue and in service instruction for pathologists regarding intraoperative reporting of high-grade dysplasia will be the subject of a prospective study for potential improvement of “sampling” and “interpretative” discrepancies, respectively. Future studies hope to minimize the cases of locoregional occurence due to inadequate margin status.
Adenosquamous carcinoma of the head and neck: epidemiological features and outcome analysis
Authors: Deb P Q
Published: November 2022

Introduction/Objective

Adenosquamous carcinoma (ADSC) is a rare, aggressive malignancy that commonly arises in the lung, pancreas, and genitourinary tract. It has rarely been reported to arise in the head and neck area. Histologically, this entity comprises two distinct components: squamous cell carcinoma (SCC) and adenocarcinoma, with each component comprising at least 10% of the tumor mass. Due to its rarity, the epidemiological features, and patient outcomes of ADSC in the head and neck region have not been studied.

Methods/Case Report

Here, we have used the National Cancer Institute's Surveillance Epidemiology and End Results database to query the data of all head and neck ADSC cases. Cases with only histological evidence of diagnosis were included in the study. We used descriptive statistics to show all patients' epidemiological and management features. Kaplan-Meier curves, cox proportional regression, and multivariate regression analysis were used to evaluate how patient outcomes are affected by the age of diagnosis, sex, race, tumor grade, and management. All data were analyzed in SPSS v.25 (IBM, NY).

Results (if a Case Study enter NA)

We identified two hundred and twenty-three cases of ADSC of head and neck with histological diagnostic evidence. The distribution of age at diagnosis was unimodal, with most patients being diagnosed before the age of 50 years. Most patients were Caucasian and male. The majority of tumors were graded as poorly differentiated, with the salivary gland and larynx being the most common two sites. We also found that surgical management of the primary site significantly improved the outcome. Other variables such as age at diagnosis, race, sex, tumor grade, and the site did not affect the disease-specific survival of the patients.

Conclusion

Our study highlights this rare entity's relevant pathological, epidemiological, and outcome features and helps us understand this neoplasm better.
Microsecretory Adenocarcinoma of the Palate: A case report illustrating a recently recognized entity
Authors: Hosseini H , Sham S , Guerrero D , Kraus D H , Krevitt L D , Fantasia J E
Published: November 2022

Introduction/Objective

Microsecretory adenocarcinoma (MCA) is a recently recognized malignancy of the salivary glands that almost exclusively arises in the oral cavity with the hard palate being the most common site. To our knowledge, there are only 24 cases of MCA reported in the English literature, all of which displayed a notably consistent histology and immunohistochemical profile. MCA is a low-grade and well-circumscribed tumor with subtle infiltration into the surrounding soft tissue. A cellular fibromyxoid stroma containing microcystic tubules with abundant intraluminal basophilic secretions are distinct histologic features. Immunohistochemically, MCA is positive for S100, p63, and SOX10, and lacks expression of p40, calponin, and mammaglobin. MEF2C-SS18 fusion gene defines MCA molecularly.

Methods/Case Report

A 43-year-old woman underwent a biopsy of a sessile, nontender, papillomatous, flesh-colored lesion of the right hard palate. No evident bone erosion or cervical lymphadenopathy were detected on imaging. Histology showed stratified squamous epithelium with focal pseudoepitheliomatous hyperplasia and an underlying salivary gland neoplasm consisting of microcystic tubules that were embedded in a scant myxoid stroma. Immunohistochemically, the neoplastic cells expressed S100, SOX10, AE1/AE3, CAM5.2, and p63, while negative for p40 and mammaglobin. In light of the histology and immunohistochemistry, a diagnosis of microsecretory adenocarcinoma was rendered. Right palatectomy and partial maxillectomy was subsequently performed. The specimen was notable for a 0.8 cm well-circumscribed, white-tan, submucosal solid mass that displayed an identical histology to the biopsy and involved the deep margin. No perineural or lymphovascular invasion was identified.

Surveillance exam and MRI show no recurrence after one year.

Results (if a Case Study enter NA)

NA

Conclusion

MCA is a newly defined entity that has an indolent clinical course with no reports of metastasis or recurrence after complete surgical resection. It is crucial to distinguish MCA from malignancies it resembles morphologically to avoid aggressive therapy. In challenging cases, molecular analysis can help the pathologist achieve the final diagnosis.
Intraosseous Xanthoma of the Mandible: A Case Report of a Rare Entity and Review of Literature
Authors: Luceno S , Kuklani R
Published: November 2022

Introduction/Objective

Intraosseous xanthoma of the mandible is an extremely rare, benign lesion with less than 40 cases reported to date. These lesions are often secondary to systemic disease such as hyperlipidemia or diabetes mellitus and commonly occur in the second and third decades of life. There is no gender predilection, and the gnathic location is often the posterior mandible. The most common radiographic presentation is a unilocular radiolucency with “punched-out” or corticated margins. These lesions are incidental findings during radiographic examination; patients are often asymptomatic at the time of diagnosis. The recommended treatment for intraosseous xanthomas consists of thorough curettage and has an overall good prognosis as recurrence is rare.

Methods/Case Report

We report a 63-year-old male with a 0.7 x 0.25 cm radiolucent, multilocular lesion. While the radiographic impression was that of an odontogenic keratocyst, histopathologic features were consistent with that of an intraosseous xanthoma lesion consisting of foamy histiocytes that were CD68 positive and S100 negative by immunohistochemistry.

Results (if a Case Study enter NA)

NA

Conclusion

This case represents the diagnostic challenges that can arise due to a nonspecific clinical and radiographic presentation. Moreover, the importance of combining histopathological findings to radiographic imaging and clinical history to achieve an accurate diagnosis and provide the most effective treatment.
Application of the Jhala Risk Scoring System (JRSS) to a SARS-CoV-2 Sequenced Population
Authors: Petersen J M , Jhala D
Published: November 2022

Introduction/Objective

Much was unknown initially regarding the triaging of scarce resources to manage the COVID-19 disease, particularly for prognosticating hospital admission needs, which contributed to the healthcare resource supply crisis. Thus, the authors developed the simple Jhala Risk Scoring System (JRSS). There is no report in the English literature that has explored a risk scoring system in patients with a SARS-CoV-2 sequencing result demonstrating different SARS-CoV-2 strains; hence, presented here is a first report.

Methods/Case Report

The JRSS assesses risk factor points based on patient’s age, ethnicity, pulmonary medical history, cardiovascular medical history, diabetes history, smoking history, and laboratory parameters. From the veteran patients who had been sequenced for COVID-19 from March 2021 to June 2022 with available clinical notes or follow-up, the JRSS was applied to obtain a JRSS score. This JRSS score was then compared with the patient’s admission status, SARS-CoV-2 sequence result, and survival. A JRSS score of 7 or greater would designate higher risk.

Results (if a Case Study enter NA)

There were a total of 11 COVID-19 positive patients meeting the inclusion criteria during the study period. 4 of these 11 patients were from March to May 2021. The patient ages ranged from 55-80 years of age and consisted of 2 Caucasian Americans and 2 African Americans. Of these 4 patients, 1 was treated as an outpatient (JRSS score 2), 2 were treated in the intensive care unit within which 1 expired (both JRSS score 9), and 1 was treated on the medical floor (JRSS score 7). All 4 patients from March to May 2021 sequenced to have Pango Lineage B.1.1.7.

7 of the 11 patients were from May to June 2022. The patient ages ranged from 69-86 years of age and consisted of 4 Caucasian Americans, 2 African Americans, and 1 decline to state. Of these 7 patients, 1 patient expired in the CLC (JRSS score 10). 5 recovered within the CLC with JRSS scores of 5, 7, and 8 for 2, 1, and 2 patients respectively.

One patient required hospitalization (JRSS of 6 based clinically only as lab parameters were not performed). All 7 patients except for 1 sequenced for BA.2.12.1, a subvariant of Omicron. The 1 patient who sequenced with a different Omicron subvariant (BA.2.9) was one of the 5 patients who recovered from infection within the CLC.

Conclusion

The JRSS, developed early in the pandemic, is a very simple and highly successful system that helps in prognostication even with the Omicron outbreak.
Neuropathology Outreach in Ghana
Authors: Goold E , Klonoski J , Palmer C , Adjei E , Guajardo A , Abrahams A
Published: November 2022

Introduction/Objective

Ghana has a population of over 31 million people and approximately 15 neurosurgeons but is currently without a dedicated neuropathologist. Here we present a month of neuropathology outreach performed at the Komfo Anokye Teaching Hospital (KATH) in Kumasi and the Korle-Bu Teaching Hospital (KBTH) in Accra.

Methods/Case Report

In February of 2022, a second-year neuropathology fellow and a board-certified neuropathologist traveled to Ghana to give 40 approximately 1.5 hour neuropathology didactic and interactive teaching sessions. A two-week format of outreach was developed for each site in Ghana and consisted of didactic lectures and interactive sessions covering the WHO 2021 brain tumor classification system, neuroautopsy, neuroinfectious disease, neurodegenerative disease, neuromuscular disease, forensic neuropathology, neurodevelopment, and unknown case conferences. Meanwhile, a pathology trainee worked remotely to organize 12 one-hour virtual general pathology lectures and develop continuing outreach. A survey of 16 questions including 12 multiple choice questions and four short answer questions was used to assess each component and the overall satisfaction of the outreach.

Results (if a Case Study enter NA)

Eight brains were examined at four neuroautopsy conferences and ten case consultations were performed upon request. Survey results showed no statistical differences amongst the 20 sessions. Comments were positive and included one respondent planning to redesign their PhD research to focus on neurodegenerative disease in Ghana and several others commenting on the utility of molecular updates. Suggestions for improvement included quizzes, including more morphology and IHC in lectures, sending digital slides before future visits, teaching spinal cord removal, and the need for continuing outreach in neuropathology, dermatopathology, cytopathology and gynecologic pathology.

Conclusion

This experience provides a useful and well-appreciated approach to delivering international neuropathology outreach. Opportunities in neuropathology on an international level range from educational to clinical practice and research.
Telepathology: A Transforming Practice for the Efficient, Safe, and Best Patient Care at the Regional Veteran Affairs Medical Center
Authors: Petersen J M , Jhala D
Published: November 2022

Introduction/Objective

Telepathology is the practice of remote pathology using telecommunication links to enable transmission of digital pathology images for primary diagnosis, quality assurance, education, research, or second opinion diagnoses. Once properly validated and implemented, telepathology has great potential to transform the practice of pathology by increasing productivity, savings in costs, improving the quality of care, and participating in innovations to improve future care. These improvements would help ensure equity throughout all remote sites that may be served by the central regional Veteran Affairs Medical Center (VAMC), even with the long-term declining number of pathologists in the country. The validation and implementation of telepathology has been further refined by recent College of American Pathologist (CAP) and American Telemedicine Association (ATA) clinical guidelines and recommendations for the validation and implementation of telepathology, but otherwise the literature is sparse for recent telepathology validation and implementation after the promulgation of these guidelines and recommendations in the Veteran Affairs setting.

Methods/Case Report

An initial narrative literature review was conducted to ascertain the current clinical guidelines and practices of telepathology to ensure that practices during validation and implementation meet and exceed the standard of care. Furthermore, meetings including the appropriate stakeholders in information technology, privacy, facilities, and pathology were held. The telepathology platform from Leica Biosystems Aperio (Deer Park IL) was brought in house at the regional VAMC’s pathology department for validation and future implementation.

Results (if a Case Study enter NA)

Planning included following all appropriate guidelines from ATA and CAP regarding telepathology to ensure that the program met the standard of care. The arrival of the instrument was installed successfully within the pathology.

Conclusion

The installation of telepathology for use at a regional VAMC represents an important step to transform pathology to increase access, including even remote access, to pathology resources and subspecialty expertise throughout the Veteran Affairs Medical System.
Mutations in Clonal Hematopoiesis-Related Genes in Acute Myeloid Leukemia: An Observational Study
Authors: Elhodaky M , Gao J
Published: November 2022

Introduction/Objective

Genes commonly mutated in clonal Hematopoiesis (CH) are found in a subset of acute myeloid leukemia (AML) patients. Although these mutations can occur early in AML evolution, they are not alone sufficient to cause AML, and their role in disease development is still poorly understood.

Methods/Case Report

We searched all AML cases with mutations in three major CH genes (DNMT3A, TET2, ASXL1). Only mutations of known or possible clinical significance were included. We evaluated the pathologic diagnosis, cytogenetics, molecular profiling, and follow-up information.

Results (if a Case Study enter NA)

Eighty-one cases were identified (59 males and 22 females, age 33-89, median 67). Blasts often show monocytic differentiation, seen frequently in AML with mutated NPM1 and AML NOS, with less frequency in t-AML (25%). Among 72 patients with available cytogenetic data, 50% had normal karyotype. MDS- related cytogenetic abnormalities were common and included complex karyotype, del(5q), del(7q), +8, and +20.

Mutations in CH genes were almost always accompanied by other driver mutations (90%), most frequently NPM1, followed by mutations in cell signaling genes (FLT3, RUNX1, KRAS, CBL, NF1, NRAS), spliceosome (SRSF2, U2AF1, ZRZF2), IDH1/2, cohesin complex-related genes (STAG1, STAG2, SMC3, SMC1A, RAD21), BCOR, TP53, WT1, PHF6, or SH2B3. Mutations in CH genes can persist after the patients achieved morphologic remission, and were often associated with disappearance of the accompanying mutations (68%). The VAF of the mutated CH-related genes, during remission, significantly decreased (p=0.00075), indicating decreasing clone size with AML treatment. In 4 of the 5 cases with relapsed disease, additional mutations in CEBPA, KRAS, RUNX1, IDH2, FLT3 ITD, and PHF6 were acquired

Conclusion

Mutations in CH-related genes are present in different types of AML, but most frequently in AML with mutated NPM1, AML-MRC and AML with monocytic differentiation. They alone are not sufficient to cause AML, and can shrink during remission. Relapse is often accompanied by acquisition of additional mutations.
Extranodal Marginal Zone Lymphoma of the Thyroid with Extensive Amyloid Deposition: A Rare Case Presentation
Authors: El-Dana F , Eltahir M , Siatecka H , Cox B , Perez M
Published: November 2022

Introduction/Objective

Extranodal marginal zone lymphoma (MZL) is a rare indolent tumor with the potential of recurrence and systemic spread. Thyroid involvement is infrequently reported, and generally seen in the context of Hashimoto thyroiditis. Additionally, amyloid deposition is an exceptional complication of extranodal MZL. We report an unusual case of a 65-year-old woman with a rapidly growing symptomatic nodule of the right thyroid lobe and a previous inconclusive FNA showing benign lymphoid tissue. She was taken to the OR for diagnostic right thyroid lobectomy with neck level 6 dissection.

Methods/Case Report

The specimen was sent for histologic evaluation, and showed thyroid with marked amyloid deposition, highlighted by Congo Red special stain, distorting normal architecture. Additionally, significant small atypical lymphoid infiltrate was present. Neoplastic lymphocytes were positive for CD20, PAX5 and CD43. Kappa light chain restriction by kappa ISH stain indicated monoclonality. Conversely, CD138, CD10, BCL6 and CyclinD were negative. Ki-67 demonstrated a 15-20% proliferation index. The germinal centers of the secondary follicles demonstrated diminished CD10 and BCL-6 consistent with follicular colonization by neoplastic lymphocytes. One of the regional lymph nodes displayed involvement by lymphoma with amyloid deposition. Medullary carcinoma of the thyroid was ruled out on the basis of incompatible histologic and immunohistochemical profile.

Results (if a Case Study enter NA)

NA

Conclusion

While Medullary carcinoma and amyloid goiter are among the top differentials for extensive amyloid deposition in the thyroid gland, we illustrate the need for judicious review of clinical history and careful consideration of immunohistochemistry workup to establish the unusual diagnosis of extranodal MZL of the thyroid with extensive amyloid deposition.
Myelodysplastic Syndrome with Monosomy 7 in a Patient with Ataxia-Pancytopenia Syndrome
Authors: Wildes T J , Rentas S , Carlsen E , Dennison J , Dixon A
Published: November 2022

Introduction/Objective

Ataxia-pancytopenia syndrome is caused by mutations in SAMD9L, a tumor suppressor gene on chromosome 7 with roles in normal hematopoiesis and cerebellar development. Syndrome manifestations consist of a combination of progressive ataxia, multilineage cytopenias, and increased risk of myeloid neoplasms associated with monosomy 7. Histopathologic and radiologic descriptions of this recently described disorder are scarce and treatment strategies are not standardized. Additionally, features that predict spontaneous hematologic remission of myeloid neoplasms are incompletely understood. Therefore, detailed discussions of this disorder and its possible outcomes are warranted.

Methods/Case Report

A six-year-old boy was brought to his doctor when his parents noticed head tilting while reading and impaired coordination. Brain MRI revealed extensive T2/FLAIR hyperintensities of white matter, cerebellar hypoplasia, and a thinned corpus callosum. Further evaluation excluded autoimmune etiologies, infectious diseases, and inherited leukodystrophies. Whole exome sequencing demonstrated a previously uncharacterized heterozygous mutation in SAMD9L, c.2062T>A; p.Tyr688Asn. Subsequent testing revealed pancytopenia. A bone marrow biopsy showed small megakaryocytes with abnormal nuclear lobation and erythroid progenitors with nuclear blebbing and binucleation. Blasts were borderline increased (4%). Fluorescence in-situ hybridization and karyotype showed monosomy 7. A myeloid next-generation sequencing panel identified an ETV6 mutation (p.Gln143Ter, VAF=5.4%). A diagnosis of myelodysplastic syndrome with monosomy 7 in the setting of ataxia-pancytopenia syndrome was rendered. The patient underwent allogeneic stem cell transplant and is doing well at last follow-up.

Results (if a Case Study enter NA)

N/A

Conclusion

Ataxia pancytopenia syndrome is a recently described and incompletely understood disorder. Some myeloid neoplasms in ataxia-pancytopenia syndrome can undergo somatic revertant mosaicism via uniparental disomy, resulting in spontaneous hematologic remission. Factors that predict spontaneous remission are unclear; however, secondary mutations have been associated with poorer outcomes. This case emphasizes the value of comprehensive genetic testing modalities in challenging cases. Screening for SAMD9L mutations in cases of pediatric myelodysplastic syndrome could be considered.
A Case of Ambiguous Lineage Acute Leukemia Posing Diagnostic Challenge
Authors: Rahman M , Huq Ronny F , Islam H
Published: November 2022

Introduction/Objective

N/A.

Methods/Case Report

Acute leukemias with ambiguous lineage encompass those leukemias that show no clear evidence of differentiation along a single lineage and account for less than 4% of all cases of acute leukemias and often poses diagnostic dilemma. We present a challenging case of an ambiguous lineage acute leukemia in a previously healthy 27-year-old male, who presented to the ED with acute fever, dyspnea on exertion, nausea and vomiting. A complete blood count (CBC) showed a white blood cell count of 323 × 109/L, Hemoglobin of 3.3 g/dl, Platelet count of 44 × 109/L and a differential count of Neutrophil: 11, Lymphocyte: 31, Monocyte: 02, Band Neutrophil:1, Myelocyte :1, Blast: 54. Bone marrow aspirate smears revealed a heterogenous population of small to large sized blasts comprising 83% of cellularity. They expressed scant to moderate basophilic cytoplasm, high N/C ratio, round to irregular nuclear contour, finely granular chromatin and some with nucleoli. Other lineages were markedly suppressed. Flow cytometric analysis revealed an abnormal blast population (~80% of total) expressing CD34, HLA-DR, Tdt (subset), CD71 (dim) and CD38. In addition, the blasts expressed myeloid associated antigens CD13, MPO (smaller subset), as well as B-cell associated antigens CD19 (dim), cytoplasmic CD22 and cytoplasmic CD79a. They also expressed T-cell associated antigens, CD2, CD3 (smaller subset), CD5 (subset) and CD7 (subset) but negative for cytoplasmic CD3. This unusual pattern of expression posed a challenge as to what type of mixed phenotype leukemia it should be with variable expressions from all three lineage of myeloid, B- and T-cell. Further work-up showed, scattered blasts are also positive for MPO by cytochemical (on aspirate smear) and immunohistochemical stain (on core). The latter also showed negativity for CD3. Based on all these findings, this mixed phenotype acute leukemia (MPAL) was best categorized as MPAL (B/myeloid) over so called “Triphenotypic (B/T/myeloid) acute leukemia”. We considered expression of myeloid and B cell markers as more lineage defining in this case as compared to small subset expressing T lineage marker CD3. This case exemplifies the importance of multimodal comprehensive analysis of acute leukemia, especially in the setting of MPAL with expression of multi- lineage markers posing a diagnostic challenge.

Results (if a Case Study enter NA)

N/A.

Conclusion

N/A.
Concurrent IRF4 Rearrangements in a Patient with B Cell and T Cell Disorders
Authors: Bernhisel A , Siddon A , Katz S
Published: November 2022

Introduction/Objective

IRF4 is a regulatory protein which required at several stages of B and T cell development and differentiation. Rearrangements of the IRF4 chromosomal region have been detected in various B and T cell neoplasms including a distinct entity in the WHO tumor classification for diffuse large B cell lymphoma (DLBCL) with IRF4 rearrangement and another for an IRF4 rearranged subtype of the CD30-positive T cell lymphoproliferative disorder, lymphomatoid papulosis (LyP).

Methods/Case Report

We present the case of a 52-year-old man with a past medical history of treated Hodgkin disease in remission who now presents with a DLBCL of the tonsil as well a cutaneous LyP, both of which demonstrate the IRF4 gene rearrangement. Immunohistochemical stains support the morphologic diagnoses and the rearrangement is detected in both cases using fluorescence in situ hybridization (FISH).

Results (if a Case Study enter NA)

NA.

Conclusion

The detection of IRF4 translocation in two separate cell lineages may result from one of a handful of possible explanations that we explore. First, a mutation in a multipotent hematopoietic progenitor cell may give rise to common lymphoid progenitors which pass the mutation on to subsequent B and T differentiated lymphocytes. Second, de novo mutations may be occurring in both B and T cell lines leading to the mature lesions. Finally, it may be possible that one of the two lesions is not truly positive for IRF4 rearrangement, but rather the background B cells in the skin or T cells in the tonsil are the cells positive for the aberration. This is a unique case of a B and T cell lesion in the same patient which both possess the same rare genetic rearrangement. The implications on our understanding of the genetic development of such lesions is significant and may subsequently impact diagnosis and therapy going forward.
Utility of Repeated NGS Testing in Myeloid Diagnostic Work Up
Authors: Zhu Y , Aljuboori O , Zhou Y
Published: November 2022

Introduction/Objective

NGS is an integral component of diagnostic work-up of myeloid neoplasms, commonly applied at initial diagnosis and for assessment of treatment response. It is less clear how NGS should be repeated at disease follow-up when initial result is negative. In order to assess the utility of repeated NGS testing, we retrospectively analyzed results in patients with multiple tests.

Methods/Case Report

Myeloid NGS results were collected between 10/2017 and 4/2022 at University of Miami. The results were grouped by patients and arranged by collection date and finding of mutations. First, we identified patients with negative result or a single mutation of common CHIP gene TET2, DNMT3A, or ASXL1 (DAT) in the first available NGS test. Then we divided these patients into negative follow-up group, if all NGS results were the same as the initial test, and positive follow-up group, if any new mutations were detected. The NGS findings were correlated with clinical history and pathology diagnosis.

Results (if a Case Study enter NA)

Results from 876 patients were analyzed. A total of 362 patients underwent multiple NGS tests; among them, 84 were negative and 14 had a single DAT mutation in the first NGS test. Among the 98 patients, 21 (21.4%) were in the positive follow-up group, with median time-to-positive at 132 days; the other were in the negative follow-up group with median follow-up time at 258 days. Analysis of the patient history showed the positive follow-up group consists 16 patients who were in remission of high-grade myeloid neoplasm at the time of initial testing and relapsed at the time of detection of mutations, 4 patients who acquired alteration of uncertain significance after hematopoietic stem cell transplant, and 1 patient who acquired KRAS mutation corresponding to MDS developed 846 days after the initial testing.

Conclusion

Positive conversion in repeated NGS testing are mostly associated with relapsed myeloid neoplasm after chemotherapy.
A Novel Fusion Partner in a Case of Myeloid/Lymphoid Neoplasm with FGFR1 Rearrangement
Authors: Chakraborty S R , Ibrahim S , Johari V , Hunt J , Freeman J
Published: November 2022

Introduction/Objective

Myeloid/lymphoid neoplasms with rearrangement of FGFR1 are uncommon and heterogeneous group of hematological malignancies that may present as myeloproliferative neoplasm, acute myeloid leukemia, T or B lymphoblastic lymphoma/leukemia, or mixed phenotypic acute leukemia. Patients can present with lymphadenopathy, mediastinal mass, or systemic symptoms. Eosinophilia is common in peripheral blood or bone marrow. Several chromosomal rearrangements and fusion genes have been described with FGFR1 rearrangement and all of them encode an aberrant tyrosine kinase. Tyrosine kinase inhibitors may offer a prospective therapeutic approach although specific targeted therapies have yet to be established.

Methods/Case Report

We present a case of a 14-year-old male who presented with rapid neck pain and swelling. Imaging revealed a 15 x 8 x 6 cm neck mass extending into the anterior mediastinum. Laboratory evaluation revealed anemia, thrombocytopenia, and leukocytosis (41.7 K/mm3), with absolute eosinophilia and blasts of 50%. Flow cytometry of peripheral blood demonstrated a population of T-lymphoblasts comprising about 60% of the cellularity with dim CD45, cytoplasmic CD3, CD7, TdT, CD38, CD4, CD5, CD10, and CD15, supporting T-lymphoblastic leukemia/lymphoma. The patient received induction chemotherapy, and subsequent bone marrow biopsy showed morphologic remission. Six weeks from diagnosis, the patient developed a gluteal mass with an atypical T-cell infiltrate that was negative for TdT; and at 15 weeks from diagnosis, developed an enlarging abdominal mass, also with an atypical T-cell infiltrate also negative for TdT and CD1a. At that time molecular diagnostic studies of the abdominal wall mass discovered a previously unpublished ATG16L1-FGFR1 fusion, supporting myeloid/lymphoid neoplasm with FGFR1 rearrangement, T-lymphoblastic leukemia/lymphoma.

Results (if a Case Study enter NA)

NA.

Conclusion

Although a variety of translocations have been identified with FGFR1 rearrangement, the novel fusion partner ATG16L1 has not been previously reported. The case also illustrates an unusual extramedullary recurrence of the T-cell lymphoblastic leukemia/lymphoma with significant antigenic shift including loss of TdT and CD1a.
Peripheral Blood Flow Cytometry Outside of Recommended Indications: A Potential Source of Increased Healthcare Costs?
Authors: Ocampo Gonzalez F , Solarewicz J , Miller I J , Lopez-Hisijos N M
Published: November 2022

Introduction/Objective

Flow cytometry (FC) is a useful tool in the diagnosis of hematological conditions. Recommended indications for peripheral blood FC have been put forth by several groups, including the American Society for Clinical Pathology (ASCP) in its Choosing Wisely Initiative, and include neutropenia, absolute lymphocytosis, lymphadenopathy and splenomegaly, as well as follow-up for known hematological malignancies. Concerns exist that the use of peripheral blood flow cytometry outside of these indications can be associated with increased health costs.

Methods/Case Report

We performed a retrospective search for all peripheral blood flow cytometry studies performed at Rush University Medical Center in the period spanning January to June, 2021. We used the Query feature on Soft Computer’s SoftFlow (SCC Soft Computer, Florida). For all cases found the electronic health record was searched for information on the clinical indication, ordering service, history of hematological malignancies, and study results.

Results (if a Case Study enter NA)

286 peripheral blood flow cytometry studies were identified, of which 187 had negative findings and 99 were abnormal. 220 cases (77%) were ordered under recommended indications (by ASCP) while 66 cases (23%) were ordered outside of them. Of the studies ordered under recommended indications, 121 (55%) had abnormal findings, while 99 (45%) were negative. Of the studies ordered outside of recommended indications, 100% had negative findings; none of these cases showed a history of hematological malignancy on record. The most common non-recommended indications were isolated anemia (31 cases, 11%), isolated thrombocytopenia (16 cases, 5.5%), bicytopenia (15 cases, 5%) and coagulopathy (4 cases, 1.5%). 42 studies (65%) were ordered by the hematology/oncology service while 22 (35%) were ordered by the internal medicine and surgery services.

Conclusion

A quarter of the peripheral blood flow cytometry studies in the selected period were performed outside of recommended indications, with negative results in 100% of them. Collectively, single or bicytopenias were the most common non-recommended indication. The majority of these studies were ordered by the hematology/oncology service, with only a third coming from others. Some possible causes for these inappropriate requests include ordering studies as a battery instead of a step-wise approach, and concern for missing an incipient/occult condition.
Immunoglobulin G4-Related Disease (IgG4-RD) Mimicking Hyaline Vascular Castleman Disease
Authors: Karimi S S , Fidai S
Published: November 2022

Introduction/Objective

Immunoglobulin G4-related disease (IgG4-RD) is a newly emerging immune-mediated fibroinflammatory disease characterized by increased IgG-4+ plasma cells. In soft tissue and visceral organs, the IgG4+ plasma cells often accompany a storiform pattern of fibrosis with obliterative phlebitis. In lymph nodes, rare cases have been described in the literature mimicking Multicentric Castleman Disease.

Methods/Case Report

Herein, we present a case of a 59-year-old male with history of lung adenocarcinoma status post resection one year prior, who presented with several months of unintentional weight loss and worsening of cervical lymphadenopathy. CT scan of the neck demonstrated extensive cervical lymphadenopathy. Incidentally, patient had traveled to a foreign country and had a positive QuantiFERON result. Clinical suspicion was either nodal metastatic disease or TB infection. An excisional biopsy of the left cervical lymph node was performed. Microscopic examination revealed numerous hyperplastic follicles with significant hyaline deposition, concentrically thickened mantle zones, radially penetrating vessels, increased interfollicular vascularity and plasmacytosis; morphologic features commonly associated with Hyaline-Vascular Castleman Disease (HVCD). Additionally, plasmacytosis within germinal center was identified. Immunohistochemical stains demonstrated significant IgG4+ plasma cells (approaching 108/HPF) within the germinal centers. All plasma cells were polytypic.

Results (if a Case Study enter NA)

N/A.

Conclusion

Commonly described patterns for IgG4-RD in the literature are multicentric Castleman disease (MCD)-like, whereas, in our case, we present intrafollicular plasma cell proliferation pattern of IgG4-RD with classic background features of HVCD. Accurate diagnosis and distinction between these two entities is imperative for prognostication, treatment and clinical management of IgG4-RD.
A Rare Case of Anaplastic Lymphoma Kinase-Positive Large B-Cell Lymphoma Involving Epidural Tissue
Authors: Satia S , Lam J
Published: November 2022

Introduction/Objective

Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK-positive LBCL) is a rare, aggressive type of non-Hodgkin’s B-cell lymphoma with characteristic rearrangements and overexpression of ALK. Diagnosis of ALK-positive LBCL is challenging because of its rarity and uncharacteristically low expression of B- lineage antigens usually needed for diagnosis of B-cell lymphomas. In this report, we describe a case of ALK-positive large B cell lymphoma involving epidural soft tissue in a young adult.

Methods/Case Report

29 year old presented to emergency department with a two week history of back pain and a three day history of worsening numbness and weakness in the lower extremities. MRI of the thoracic spine showed an epidural soft tissue mass posterior to T5, T6 and T7 vertebral bodies with abnormal signal in the T6 spinous process. Histological examination from the epidural mass revealed sheets of atypical lymphoid cells with abundant pale cytoplasm and round vesicular nuclei with prominent single to occasional multiple nucleoli. Immunohistochemical stains demonstrated neoplastic cell positivity for ALK, VS38c, CD138, EMA, MUM1, CD45, PAX5 and MCK. They were negative for CD3, CD20, CD19, CD79a, CD30, CD2, CD117, SOX10, HMB45, cytokeratin, synaptophysin and chromogranin. These overall findings were consistent with ALK-positive large B-cell lymphoma.

Results (if a Case Study enter NA)

NA.

Conclusion

ALK-positive large B-cell lymphoma is a non-Hodgkin lymphoma associated with high morbidity and mortality. Absence of reliable B-cell marker expression in this B-cell lymphoma requires recognition of morphological findings to order confirmatory testing such as immunohistochemical stains for CD138 and ALK. This particular case also showed an unusual anatomic presentation in epidural tissue.
A Two Part Case Series on Acquired Hemophilia A
Authors: Dailey D S
Published: November 2022

Introduction/Objective

Acquired Hemophilia A is a rare condition with an incidence of 1 per 1.5 million per year. The average age at presentation is 74 years. It is due to spontaneous production of IgG autoantibodies that target endogenous factor viii. This disease should be considered when a patient presents with bleeding, an abnormal prolongation of activated partial thromboplastin time and /or no prior personal or family history of bleeding. Autoimmune disorders and malignancy are common associations. Pregnancy and surgery are common presenting scenarios.

Methods/Case Report

Case 1: 71 year old female with a history of deep venous thrombosis, and rheumatoid arthritis. Patient presented to the emergency department with a hemoglobin of 4.7 and coagulation studies showed a prolonged partial thromboplastin time of 119 seconds. Imaging revealed retroperitoneal bleeding. A mixing study showed no correction of partial thromboplastin time. The patient was treated with packed red blood cell transfusions until hemodynamically stable. Further coagulation studies revealed a factor VIII activity of 3L and factor VIII inhibitor level of 103 bethesda units. This confirmed suspicion of an acquired factor VIII inhibitor associated with the patient’s rheumatoid arthritis as the source of abnormal lab values and bleeding. Patient was treated with recombinant factor VIIa, novoseven, along with continuous prednisone and cyclophosphamide. Case 2: 82 year old male with history of IgG Kappa Monoclonal Gammopathy of Undetermined Significance. Patient presented with gastrointestinal bleeding and 4g/Dl hemoglobin. He received 5 units of packed red blood cells. Sigmoidoscopy revealed a rectal ulcer causing lower gastrointestinal bleeding. An advanced coagulation study revealed factor VIII activity of 1%, and inhibitor levels of 17 bethesda units. Patient was started on prednisone initially, followed by cyclophosphamide. However, bleeding continued. He was treated with 6 units of recombinant factor VIIa and packed red blood cell transfusions as required to keep hemoglobin levels at 7g/Dl. He was continued on prednisone at an increased dosage and discharged.

Results (if a Case Study enter NA)

NA.

Conclusion

Acquired Hemophilia A is a rare disease. It should be suspected anytime there is unprecedented bleeding and/or unexplained prolongation of partial thromboplastin time. It is diagnosed with factor VIII panel, including inhibitor. Treatment includes immunosuppresants, intravenous immunoglobulins, and recombinant factor VIIa.
Artificial Intelligence with CBC Based Morphometric Parameters Aimed Toward Effective Diagnostic Practices for Dysplasia Associated Hematological Malignancies
Authors: Haider R
Published: November 2022

Introduction/Objective

The diagnosis and classification of dysplasia associated hematological neoplasms is dominated by morphology. Current round of study made use of potential ‘fingerprints’ among routinely generated diagnostic data particularly morphological and immature fraction-related (morphometric) parameters produced during routine complete blood count (CBC) testing in hemat-oncology department through artificial intelligence predictive modeling.

Methods/Case Report

Along conventional statistics, neural network models were trained on anonymized demographical, clinical and diagnostic data of total 1624 individuals with common hematological neoplasms. In addition, validation conducted on independent dataset. The frameworks were trained to differentiate hematological malignancies cases with various sub-entities of Dysplasia against Non-dysplastic group as a control cohort.

Results (if a Case Study enter NA)

Our predictive model attained greater precisions; percent incorrect prediction were remained 10.3 and 4.6 for training and testing phases, respectively along with a 95.4% negative predictive value (NPV). Moreover, higher accuracy (93.1%) was obtained during prospective validation in challenge of independent dataset. Model’s performance related metrics: the gain and lift chart, predictive-pseudo probability chart, and receiver operative curve (ROC) curve were noted as persuasive. Considering the sensitivity and specificity, area under the curve (AUC) values were also noted quite convincing; 0.954 for Non-dysplasia group while 0.994 for acute myeloid leukemia with dysplasia (AML-Dys) followed by 0.992, 0.988, 0.986, 0.984, 0.973, and 0.962 for chronic myelo- monocytic leukemia (CMML), refractory anemia with excess blast-I (RAEB-I), refractory anemia with excess blast-II (RAEB-II), refractory anemia with multi-lineage dysplasia (RCMD), Hypoplastic myelodysplastic syndrome (H-MDS), and refractory anemia with uni-lineage dysplasia (RCUD) respectively.

Conclusion

The negative predictive efficiency of our framework advocates its utility as a screening tool for the rapid expulsion of Dysplasia associated hematological neoplasms in hemat-oncology sections, aiding prompt care decisions.