bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunoreactivity of Histiocytes to OCT4; a diagnostic pitfall
Authors: Al-kharouf I , Stoieva M , Hamza A
Published: November 2023

Introduction/Objective

Immunohistochemical stains are supposed to make a Pathologists’ life easier; however, interpretation of some stains in isolation can be a diagnostic pitfall. Immunoreactivity of paraganglia to OCT4 stain is a known pitfall for this stain when evaluating retroperitoneal lymph node dissection specimens for germ cell tumour metastasis. The purpose of this report is to highlight another pitfall of the OCT4 stain, albeit in a similar clinical scenario.

Methods/Case Report

A 49-year-old male with a history of left testicular seminoma metastatic to periaortic, retroperitoneal and left supraclavicular lymph nodes, status post orchiectomy and chemotherapy, presented with a rising B-HCG and PET scan evidence of recurrent/refractory disease. His imaging showed interval increase in FDG uptake of left periaortic lymph nodes despite a decrease in size. A biopsy was performed. Pathologic evaluation showed predominantly necrotic tissue with rare clusters of atypical cells with clear to pink cytoplasm, monotonous nuclei, and rare admixed lymphocytes. Immunohistochemical stains showed the atypical cells to be positive for OCT4 stain, raising the possibility of viable seminoma. However, additional satins showed the cells to be positive for CD68 and CD163, and negative for CD117, SALL-4, pancytokeratin, SF-1, GATA3 and synaptophysin. Therefore, the atypical cells were interpreted to represent histiocytes; no viable germ cell tumor was identified.

Results (if a Case Study enter NA)

NA

Conclusion

This case highlights the importance of using a panel of immunohistochemical stains, instead of relying on one stain, even if the stain is thought to be fairly specific. Pathologists need to be aware of immunoreactivity of histiocytes to OCT4 as a potential diagnostic pitfall in addition to the paraganglion cells staining for OCT4 being a pitfall.
Ethnic Incidence of Metastatic Prostate Carcinoma in a Veteran Affairs Medical Center’s (VAMC) And Early Surveillance Guided by Sites of Metastases
Authors: Dalal S , Petersen J M , Jhala D
Published: November 2023

Introduction/Objective

Ethnic difference in incidence, mortality, and prognosis for prostate adenocarcinoma is well known with disparities between African American (AA), Caucasian and Asian origin population reported by tumor heterogeneity and increased number of gene mutations in genomic profiling. Early metastasis of prostate cancer with younger age at the presentation in AA ethnicity has been noted. Earlier screening, biopsy and tumor molecular profiling may lead to a decrease in morbidity and mortality related to metastatic prostate cancer. While there are known differences in the incidence of prostate cancer between different ethnic groups and differences in ethnic access to care and diagnosis varies widely between distinct medical practices, the ethnic incidence of diagnoses of metastatic prostatic adenocarcinoma and distribution of sites particularly in a Veteran population has not been well studied.

Methods/Case Report

A retrospective search was performed from December 2019 to October 2022 for metastatic prostatic carcinoma specimens at regional Veteran Affairs Medical Center (VAMC). Both H & E and immunohistochemical antibodies for prostate were reviewed and used in the diagnosis of metastatic carcinoma of prostate origin.

Results (if a Case Study enter NA)

A total of 21 cases with metastatic prostatic adenocarcinoma were found from which 9 were metastases to bone, 5 were metastases to lymph node and 7 were metastatic to other organ sites. Majority of the cases were of ethnic African American veterans (12/21, 57%), followed by Caucasian Americans (7/21, 33%), and 2 of unknown ethnicity (2/21, 10%). On examination, most frequent site of metastases by ethnic African Americans was lymph node in 4 out of the 5 (80%) total cases metastatic to lymph node, and 5 out of 6 total cases (83%) with metastases to different organ sites together. On the other hand, ethnic Caucasian Americans the most common metastatic site was bone with 6 out of 10 total cases (60%) metastatic to bone.

Conclusion

African American Veteran patients have a higher incidence of metastatic prostate carcinoma and a higher incidence of earlier metastases. A similar trend was seen in the study population with African Americans making up most of the study population and also suggestively having more cases of lymph node and other organ metastases. The increased proportion of African Americans in the study population with lymph node metastases suggests targeting lymph nodes for biopsy for early detection of the metastatic prostatic carcinoma.
Bilateral Gonadoblastoma in a 13-Year-Old Female with Turner Syndrome and Y Chromosome: A Case Report
Authors: Pokharel A , Lamb C A , Micale M A , Zhang P L
Published: November 2023

Introduction/Objective

Gonadoblastoma is a relatively rare type of ovarian tumor that has a high risk for patients with 45X/46XY. It is derived from the Y chromosome at its long arm GBY region, which contains the most likely candidate gene called testis-specific protein Y-encoded (TSPY).

Methods/Case Report

In this case report, we present a case of a 13-year-old girl with Turner syndrome whose cytogenetic test showed 45X with monosomy X and a siodicentric Yq chromosome. As she carried a high risk for the development of gonadoblastoma due to the presence of the Y chromosome and clinically had premature ovarian failure, she received further imaging studies, which did not reveal obvious ovarian masses. She underwent resections of bilateral fallopian tubes and ovaries. Bilateral fallopian tubes were unremarkable. However, within the bilateral ovarian tissue, foci of gonadoblastoma were found (0.5 to 0.6 cm), composed of large round germ cells (confirmed by positive OCT 3/4 and SALL4 stains) intermingled with oval-shaped sex cord-stromal cells forming tubular/cribriform structures (confirmed by positive staining for inhibin, calretinin, and FOXL2). The stromal cells of gonadoblastoma, but not germ cells, were positive for androgen receptor staining, while both components were negative for estrogen receptor staining. No invasive germ cell tumor or sex cord tumor was present.

Results (if a Case Study enter NA)

N/A

Conclusion

The positive androgen receptor staining in stromal cells of the gonadoblastoma supports the view that the Y chromosome-driven androgen system may play a role in the development of gonadoblastoma in a bi-cellular pattern.
Enteric adenocarcinoma of the Thymus
Authors: Abu-Salah A , Kraft A , Mesa H , Loehrer P
Published: November 2023

Introduction/Objective

Thymic adenocarcinomas are extremely rare. Enteric type thymic adenocarcinoma is an even more rare subtype morphologically and immunophenotypically indistinguishable from colorectal primaries.

Methods/Case Report

We report a case of a 63-year-old female who presented with shortness of breath and cough. Computerized tomography (CT) scan showed an 11 x 6 cm right-sided anterior mediastinal mass extending from the great vessels to the diaphragm. Within the mass, there was a 4.8 cm possible thymic cyst that had been originally identified in 2005. Multiple right pleural and bilateral intrapulmonary nodules, and a 2 cm pericardial lymph node were also observed. A core biopsy showed a mucinous adenocarcinoma that was positive for the colorectal markers CK20, CDX2, MUC-2 and the thymic marker C-KIT, and negative for CD5, PAX8, CK7, TTF-1, and ER immunostains. The tumor was negative for PDL1 22c3 (CPS<1) and positive for TROP2. PET-CT did not reveal any other primary. A diagnosis of enteric adenocarcinoma of the thymus Masaoka stage IV was established and the patient is scheduled to receive chemotherapy. Genomic testing is pending to guide potential targeted therapy.

Results (if a Case Study enter NA)

NA

Conclusion

A recent compilation of 29 cases mostly from the literature described aggressive clinical behavior, high association with thymic cysts, and coexpression of CD117 and enteric markers similar to this case. All patients had poor response to conventional platinum-taxanes regimens. Two patients received targeted therapy without benefit. None of these patient received colorectal type regimens. Although the number of reported cases is still very small, these results suggest that optimal therapy for these aggressive tumors has yet to be defined.
Odontogenic Carcinoma with Dentinoid of the Left Maxilla
Authors: Fernandez-Hazoury D A , Ji P , Chiu R
Published: November 2023

Introduction/Objective

Odontogenic carcinoma with dentinoid is a very rare dentinoid producing odontogenic tumor with 10 cases reported in literature, and it is not currently defined by the World Health Organization. It has been described to have a locally aggressive and non-metastatic course with high level of recurrence after excision.

Methods/Case Report

We report a case of odontogenic carcinoma with dentinoid located in the left maxilla of an otherwise healthy, 22-year-old male. The patient initially endorsed left upper molar tooth pain for 2 months that led him to receive medical attention. Initial examination revealed a 3 x 2 cm firm, non-mobile and non-pulsatile lesion on buccal and lingual surface of the left maxilla with imaging revealing a 2.9 x 2.7 x 2.7 cm mixed radiolucent/radiopaque lesion in the posterior left maxilla with expansion on the buccal and palatal surfaces. Incisional biopsy of the left maxilla (soft tissue) was initially diagnosed as suspicious for osteosarcoma, which was later changed to odontogenic carcinoma with dentinoid. One year later, the mass had increased to 4.5 x 3 x 4 cm in size. Left hemi maxillectomy was performed, and the specimen was diagnosed with odontogenic carcinoma with dentinoid. Previously described histological features of clear cell change, low grade appearance, focal calcification, and dentinoid formation are present in our case. Our case is the first to describe glandular formation of the tumor cells.

Results (if a Case Study enter NA)

NA

Conclusion

The histopathological changes of our case reflect previously reported microscopic descriptions for this exceedingly rare tumor that is unclassified by the World Health Organization. It has been reported to occur in both male and female patients without predilection and a wide age range from 14-61 years. To our knowledge, this is the 11th reported case, and the 5th case described in the maxilla. Further studies, including NGS sequencing to determine genetic alterations, will be performed on our case to further elucidate pathophysiological mechanisms. Long term follow up with our patient will be attempted to determine tumor behavior.
Technical and Professional Components in Pathology Practices – Business and Educational Opportunities for Community Based Pathologists
Authors: Zahid H , Loos C , Cornish C , Wells A , Herschap B , Ehsan A
Published: November 2023

Introduction/Objective

Community based Pathologists (CBPs) are challenged by limited resources, decreasing revenue, continuous learning, workload burnout and acquisition by corporate health care groups. Pathology residency programs (PRPs) are traditionally offered at academic centers and are focused on teaching, research, clinical work, and residents are graduated with core diagnostic competencies. Upto 60% graduates usually join private practices, therefore, understanding the business aspects of pathology and abreast with innovative technologies continue to be challenge among CBPs. We conducted and presented our survey to evaluate opportunities and challenges for CBPs for adopting various technical and professional components (TC and PC) in their practices.

Methods/Case Report

Survey was conducted via interview for a total of 42 CBPs. Questions related to TC and PC were divided into 1) Immunohistochemical stains (IHC); 2) Flow cytometry (FC); 3) Fluorescence in-situ hybridization (FISH); and 4) Clinical pathology professional component (CPPC).

Results (if a Case Study enter NA)

CBPs understands the importance of TC and PC services, however 25/42 (60%) have been using it to some extent. Of those that are utilizing such TC services, 10/25 (40%) were using IHC and FC; 4/25 (16%) were using FISH. The CPPC was used by 26/42 (61%)

Conclusion

We concluded that there are several reasons for CBPs who are not utilizing TC and PC services to its full capacity such as 1) not trained well enough to read TC of IHC, FL and FISH; 2) No formal educational opportunities available to train CBPs; 3) Cumbersome lab portals to access data; 4) Billing of such services becomes complicated;

5) Workload burnout and no added incentives by practices; and 6) Limited resources to capture CPPC due to interface and integration of billing software’s. We suggest PRPs to offer electives and incorporate private practice experience for trainees, so they are prepared to embrace such business and educational opportunities.
Primary Central Nervous System ALK-negative Anaplastic Large Cell Lymphoma, with TP53 Deletion
Authors: Li L , Baisre A , Nimchinsky E A , Liu J K
Published: November 2023

Introduction/Objective

ALK-negative anaplastic large cell lymphoma (ALCL) primary to the central nervous system (CNS), is a sporadic and rare lymphoma, characterized by neoplastic T-cells which are CD30 positive and ALK negative. It has a male predominance, mostly affects old adults and usually displays supratentorial, single or multiple lesions.

Methods/Case Report

We report the case of a 57-year-old woman with medical history of breast cancer, S/P lumpectomy and radiation therapy, who came to our institution with confusion, partial aphasia and headache. MRI showed a thick-walled, irregular, ring enhancing mass in the periventricular white matter of the occipital and temporal horns of the lateral ventricle with surrounding vasogenic edema and mass effect. It was isointense to cortex on T1- and heterogeneously hyperintense on T2-weighted images with mild diffusion restriction in the enhancing portion. A left parieto-occipital decompressive craniotomy was performed and tissue was procured for diagnosis. The biopsy showed an infiltrating, angiocentric neoplasm, composed of large anaplastic cells, including hallmark cells with "horseshoe" nuclei, abundant eosinophilic cytoplasm and occasional perinuclear clearing. Large areas of necrosis and pericellular reticulin deposits of the vascular walls were also noted. On immunohistochemistry, the neoplastic cells diffusely expressed CD45, CD2, CD3, CD25, CD43, MUM1, and CD30, and were negative for ALK, CD20, CD79a, PAX-5, CD15, CD5, BCL-6, BCL-2, Granzyme B, GFAP, Pancytokeratin. In situ hybridization for EBER was negative. The proliferative index (Ki-67), while variable, was as high as 80%. TP53 deletion was detected by FISH in 100% of the cells analyzed. No rearrangements in the ALK or MYC genes was noted by FISH. Additional studies revealed a complex karyotype including loss of chromosomes 9 and 10, gain of chromosome 17 and a marker chromosome, and structural rearrangements involving chromosomes 4, 10, and 13. Previously reported rearrangements involving DUSP22 (6p25) and TP63 (3q28) were not identified. TCR gene rearrangement was also identified by PCR. High dose Cytarabine/Methotrexate, and radiation were not successful in controlling disease progression and home hospice was recommended.

Results (if a Case Study enter NA)

N/A

Conclusion

This is an infrequent type of primary CNS lymphoma with a poor prognosis and, while TP53 has been reported in sporadic, and cutaneous ALCL, to our knowledge, this is the first report of primary CNS ALK-negative anaplastic large cell lymphoma with TP53 deletion.
Lymph Nodes Triaging by General Surgical Pathologists – Flow Cytometry or Immunohistochemistry or Both?
Authors: Adhikari B , Herschap B , Sanchez-Salazar A , Ehsan A
Published: November 2023

Introduction/Objective

The diagnosis of lymphoma has become complex due to existing WHO/ICC classifications. Triaging Lymph Nodes (LN) is an important first step in making the correct and precise diagnosis in a timely and cost- effective manner, initiating appropriate treatment and predicting prognosis. Surgical Pathologists (SPs) face challenges when it comes to triaging LNs for Flow Cytometry (FC) and Immunohistochemistry (IHC), as limited guidelines are available for triaging and every practice doesn’t have hematopathologist (HP) on site.

Methods/Case Report

We retrospectively evaluated 850 LNs (excision, core or FNAs) during 2009-2022; and divided samples into two groups (without additional esoteric testing) that were blinded from each other: Group I: FC and morphology (460) and Group 2: IHC and morphology (390). Diagnostic categories (DC) were 1) Reactive (RE-140); 2) B-cell lymphomas (BLy-375); 3) T-cell lymphomas (TLy-75); 4) Hodgkin Lymphomas (HL-230) & 5) Non-heme malignancy (NHM-30).

Results (if a Case Study enter NA)

Group I – Diagnosis was made independently in 5 DCs as follows: RE (90%); BLy (45%); TLy (10%); HL (10%) and NHM (20%). Group II – Diagnosis was made independently in 5 DCs as follows: RE (70%); Bly (80%); TLy (70%); HL (90%) and NHM (100%).

Conclusion

We concluded that touch imprints or cytological preparation are important steps when triaging LNs and summarize our findings as follows: 1) Combination of both FC and IHC are useful when triaging LNs; 2) FC overall results in cost savings; 3) FC is a powerful tool to be used for initial work-up and guiding further IHC work-up and diagnosis can be rendered faster when FC data is available; 4) FC is more valuable in RE and low grade BLy, while IHC in high grade BLy; 5) IHC is more valuable in TLy, HL and NHM. Therefore, it is imperative for pathology practices to prioritize the triaging of LNs initially for FC followed by IHC as needed.
POEMS-associated Multicentric Castleman Disease: A diagnostic and Therapeutic Conundrum
Authors: Zahid H , Latif S , Baby S
Published: November 2023

Introduction/Objective

A rare multisystemic, paraneoplastic hematologic disorder, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is associated with an overproduction of pro-inflammatory cytokines caused by a plasma cell proliferative disorder. Castleman disease is a rare clinical entity described as a polyclonal lymphoid proliferation, that leads to generalized lymphadenopathy. It is rarely presented in association with POEMS Syndrome.

Methods/Case Report

A 55-year-old hispanic male, when being evaluated for liver mass, revealed bile duct thickening and a pancreatic head mass. Endoscopic fine needle aspiration biopsies were negative; however, the cross sectional imaging identified enlarged left axillary lymph nodes. His excisional lymph node biopsy showed human herpese virus-8 (HHV-8) negative multicentric Castleman disease (MCD). Several features of POEMS syndrome were noted. The axillary lymph node biopsy demonstrated florid follicular hyperplasia, scattered regressed germinal centers and concentric rings of mantle zone lymphocytes. CD138, kappa-ISH, and lambda-ISH highlight scattered polytypic plasma cells. Our case fulfills the mandatory criteria of POEMS syndrome with the presence of neuropathy and a constellation of other major and minor criterion including, axillary Castleman, splenomegaly, hepatomegaly, skin changes, ascites and bilateral renal cortical lesions. Furthermore the patient also has a history of cerebrovascular accident and chronic cough favoring POEMS syndrome.

Results (if a Case Study enter NA)

NA

Conclusion

The complexity and multi-organ involvement, leads to frequent misdiagnosis of POEMS disease. In addition significant overlap of symptoms of POEMS syndrome makes it difficult to differentiate from other plasma cell disorders associated with MCD. Our study includes a brief review of the literature delineating the characteristics and overlap between POEMS syndrome and other diseases.
CD8+ aggressive T-cell lymphoma (T-NHL) involving the liver and skin: a case study
Authors: Ibrahim N , Wang W , Naik U , Abu Qubo A , Zhu H
Published: November 2023

Introduction/Objective

Aggressive T-NHL involving cutaneous and visceral organs is rare. We report a case with a complex presentation that was found to have hepatic and skin lesions simultaneously. We emphasize the importance of the clinicopathological correlation and diagnostic work-up for such a rare case

Methods/Case Report

A 60-year-old male with alcoholic cirrhosis presented with abdominal pain, fever, and night sweats for over two weeks. Detailed physical evaluation revealed a tender, indurated, erythematous papule on the left upper back. Lab results showed leukopenia, anemia, and increased LDH. PET-CT showed multiple hypermetabolic lesions in the liver, skin, and deep soft tissue above and below the diaphragm. A liver biopsy revealed a diffuse sheath of large atypical lymphoid cells with small lymphocytes in the background. Atypical lymphoid cells stained positive for CD45, CD2, CD3, CD8, TIA-1, CD5 (partial), granzyme B (partial), βF1 (partial); and negative for ALK, BCL-2, CD4, CD7, CD10, CD30, CD56, and TCRδ. Ki-67 was 70%. The skin punch biopsy revealed epidermotropic infiltration of lymphocytes with a similar immunophenotype as the liver lesion. Bone marrow biopsy showed no involvement.

The differential diagnosis includes primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-NHL with visceral dissemination, peripheral CD8+ T-NHL, lymphomatoid papulosis, CD8-positive mycosis fungoides, and hepatosplenic T-NHL. The visceral involvement excludes lymphomatoid papulosis and CD8-positive mycosis fungoides. The absence of bone marrow involvement excludes hepatosplenic T-NHL. The prominent liver involvement favors the diagnosis of peripheral CD8+ T-NHL. However CD8+ aggressive epidermotropic cytotoxic T-NHL still cannot be entirely excluded due to the epidermotropic CD8 positive T-cell infiltration of the dermis and subcutaneous adipose tissue. Further evaluation for JAK2 mutation and TBX21 amplification can help distinguish it from Peripheral CD8- positive T-NHL.

Results (if a Case Study enter NA)

NA

Conclusion

The subclassification of CD8+ T-NHL into distinct entities with overlapping clinical and histological characteristics is challenging without molecular tests.

However, clinicopathological correlation with appropriate work-up can help narrow the differential diagnoses.
Epidural mass in a 37-year-old male with progressive neurologic symptoms
Authors: Johal J J
Published: November 2023

Introduction/Objective

A 37 yo male with progressive thoracic myelopathy (bilateral lower extremity weakness, hyperreflexia, left foot drop and bowel/bladder incontinence) visited our hospital. MRI of the thoracic spine revealed an intradural-extramedullary mass measuring 3.3 x 2.1 x 1.1 cm with severe compression and leftward and anterior displacement of the spinal cord suggestive of spinal nerve sheath tumor versus less likely meningioma. Surgery was done and an extradural mass was found which was resected via T5/6 laminectomy.

Methods/Case Report

Pathology received a red black irregular mass measuring 2.9 x 1.1 x 1.0 cm. H&E showed predominantly distended vascular channels lined by a single layer of flat endothelial cells and filled with red blood cells. Immunohistochemical stains CD34, S100, SOX10 and EMA were performed. CD34 was positive in endothelial cells lining the ectatic channels. S100 and SOX10 are negative ruling out spinal nerve sheath tumor. EMA was negative effectively ruling out a meningioma. The diagnosis of cavernous hemangioma was made.

Results (if a Case Study enter NA)

NA

Conclusion

Hemangiomas are benign tumors of circumscribed proliferating blood vessels and are most often found superficially in head and neck region. Cavernous hemangiomas have markedly dilated vessels as in our case.

Cavernous hemangiomas of the spine are very rare and represent 5-12% of vascular lesions in the spine, with majority being an extensions from a vertebral hemangioma extending into spinal canal. Only 1-2 % are purely extradural spinal locations. Out of 54 cases, 36 were male and18 female, ages 5-78 showed 80% in the thoracic spine and 93% on the dorsal side. Patients typically present with insidious back pain, radiculopathy and myelopathy suspicious for disc herniation. They are most commonly found on the dorsal side of the thoracic spine. Epidural cavernous hemangiomas on MRI would often present as a mass and should be considered in the differential diagnosis along with nerve sheath tumors, meningiomas, abscess, and extradural hematoma.
False Negative Results of First-Tier Treponemal Antibodies in an HIV-Infected Patient
Authors: Daou L , Caturegli P P
Published: November 2023

Introduction/Objective

Syphilis diagnosis relies on detecting Treponema pallidum antibodies in serum or CSF. In the reverse syphilis screening algorithm, an automated enzyme immunoassay first detects serum antibodies against treponemal antigens. A negative result halts further testing; however, a positive result prompts manual testing for antibodies against non-treponemal antigens such as cardiolipin. The sensitivity of first-tier automated assays is typically high. We present a case of an HIV patient who initially tested negative for syphilis in the first-tier assay but was subsequently diagnosed with the infection.

Methods/Case Report

A 30-year-old HIV-positive female (CD4+ count 24/mm3), previously diagnosed with chlamydia and gonorrhea, experienced blurred vision, eye pain, fever, and a palmoplantar rash. Despite clinical suspicion of syphilis, the initial first-tier chemiluminescence immunoassay (CIA) for treponemal antibodies (LIAISON Treponema, DiaSorin, Stillwater, MN) returned a negative result, precluding any further syphilis testing at that time. However, a skin biopsy revealed interface dermatitis and spirochetes. CSF analysis showed pleocytosis, increased proteins, and borderline low glucose, with both VDRL and IFA assays negative. Based on these findings, we retested for serum antibodies by repeating the CIA test and performing RPR and TP-PA assays outside the algorithm sequence. Despite reconfirmation of the CIA negativity, both RPR (titer 1:64) and TP-PA were positive, leading to a secondary syphilis diagnosis and penicillin G treatment. Subsequent investigations aimed to explain the initial false negative CIA result. Serial dilution of the patient's serum up to 1:1000 did not alter the result, excluding the 'hook effect' caused by an excessive concentration of antibodies. Further serum testing at a different laboratory using another type of first-tier immunoassay yielded a positive result, pointing toward differences in the composition of treponemal antigens utilized across various manufacturer assays as the likely cause of the discrepancy.

Results (if a Case Study enter NA)

NA

Conclusion

Given their high sensitivity, automated first-tier treponemal assays rarely yield false negative results, whereas false positives are the most common ‘lab error’ and are typically resolved with second-tier assays.

Nevertheless, this case highlights that false negatives can occur and, thus, stresses the need to re-evaluate the approach in diagnosing syphilis, especially in patients with antibody production abnormalities, such as those with HIV.
Pre-Accessioning in Anatomic Pathology – Utilizing a Cloud-Based Laboratory Information System Reducing Error in Anatomic Pathology and Improving Patient Safety
Authors: Khatri R , Guerrero B , Garcia T , Perez J , Malik A , Ehsan A
Published: November 2023

Introduction/Objective

Typical workflow in Anatomic Pathology (AP) starts from accessioning of cases to sign out. Most Laboratory Information System (LIS) follow this cycle of sample tracking. However, at certain times, either samples are not received or get lost in transit without lab being notified. There is a need of pre-accessioning in AP especially for samples received from outpatients’ sites, so labs not only track samples during transit but also reduce typographical errors (name, DOB, Unique ID) and assess workload before arrival.

Methods/Case Report

From 2020-2022, we initiated e-requisition utilizing online cloud-based portal for submitting AP cases obtained at physician offices, clinics, and outreach satellite sites. Insurance information and clinical history were scanned and uploaded with e-requisition submission. Retrospective analysis was performed, and data was analyzed and compared for errors, QA metrics and workflow analysis on samples obtained with PRE (840 cases) and without pre-accessioning NON-PRE (1280 cases).

Results (if a Case Study enter NA)

PRE and NON-PRE (handwritten and manual submission) were compared. Results were as follows for PRE vs NON-PRE: 1) Typographical errors (0.1% vs 8%); 2) Insufficient clinical history and ICD-10 (1% vs 9%); 3) Sample types errors (0.2% vs 5%); and 4) Efficient workflow for data entry per case at accessioning (1min vs 4min)

Conclusion

We demonstrated pre-accessioning feature for AP samples utilizing cloud-based portal of LIS is an important tool that can 1) prevent/reduce laboratory accessioning errors; 2) help labs monitor sample tracking from the time sample is obtained to the time it got accessioned in the lab; 3) help labs improve turn around time in their workflow for quick accessioning and 4) improve patient safety by reducing errors for AP samples; and 5) can be integrated with any clinical electronic medical record.
Beyond the Obvious: Spectrum of Neuroendocrine Proliferation and Tumors in the Biliary Tree - A Case Series
Authors: Liu Y , Pyatibrat S , Shilpa J , Lin J , Panarelli N , Karamchandani D M
Published: November 2023

Introduction/Objective

Neuroendocrine tumors (NETs) in the biliary system are extremely uncommon and often pose a diagnostic challenge due to their non-specific presentation and radiological features. While typically NETs form mass lesions causing biliary obstruction, to the best of our knowledge, microscopic neuroendocrine cell proliferation without mass formation has not been formally reported in the literature. This study aims to describe the clinicopathological features of a series of NETs/neuroendocrine cell proliferation involving the biliary tree.

Methods/Case Report

Surgical resections of NETs/neuroendocrine cell proliferation affecting the extrahepatic bile ducts and gallbladder were identified from the electronic pathology databases of five institutions between January 2010 and May 2023. The clinical data was obtained through chart review, and histologic findings were reviewed by a gastrointestinal pathologist at each institution.

Results (if a Case Study enter NA)

The study involved six patients with a mean age of 66 years (range: 58-75 years, males:3, females:3). The patients presented with abdominal pain or biliary obstruction. Pathologic examination revealed that three cases showed visible mass-forming lesions (1.6-2.4 cm) in the gallbladder or common bile duct, diagnosed as well-differentiated NETs. The remaining three cases had no grossly visible masses but showed incidental microscopic neuroendocrine cell proliferation/NETs (either in cystic duct or common bile duct) ranging from 0.2-0.4 cm, all associated with biliary lithiasis. All patients recovered after surgical resection without metastasis or recurrence, except for one patient who died a month after surgery due to an unrelated cause (multisystem organ failure).

Conclusion

This study highlights the spectrum of neuroendocrine proliferation in the biliary tree, ranging from microscopic incidental findings to grossly visible mass-forming NETs, which may result in variable clinical management and outcomes. Notably, incidental neuroendocrine proliferations were found to be associated with biliary lithiasis in all 3 cases, raising a possibility of a potential neuroendocrine metaplastic pathogenesis, which should be explored more via additional studies.
Physico-Chemical Alternatives for Synthesis of Metal Nanoparticles Using Fusarium Chlamydosporum
Authors: Abdelmonem M , Elshikh H H , Mostafa M A , Eldaly R , Hammad S E , El-Rouby M N , Wasim H
Published: November 2023

Introduction/Objective

Background: Synthesizing metal nanoparticles (NPs) by chemical or physical methods is difficult due to energy and time consumption, equipment costs, and chemical toxicity. Chemosynthesis-derived NPs are unstable, limiting their biological applications. Thus, identifying alternative green sources to address these drawbacks is difficult scientifically. The hardest part of green metal nanoparticle synthesis is finding a nontoxic natural product and an eco-friendly solvent.

Objectives: Isolation of fungal endophytes from Eucalyptus sideroxylon leaves to synthesize ZnO and Au nanoparticles.

Methods/Case Report

Materials and methods: We used healthy Eucalyptus sideroxylon plant samples from the desert research center to separate endophytes. All fungi were grown on malt extract broth on a rotary shaker at 28 °C (120 rpm) for 96 hours after isolation. Biomass components were removed by filtration and washing in distilled water. Nanoparticles came from biomass cell filtrate.

0.1 M, 1 mL of Zn SO4, and HAuCl4 were added to 10 mL of fungal filtrate and agitated for 24 hours in the dark at room temperature to make Zn and Au nanoparticles separately. Characterization of nanoparticles shows a green synthesis of ZnONPs and AuNPs.

Results (if a Case Study enter NA)

Results: Fungal endophytes' filtrates were mixed with 1mM Zn SO4 and HAuCl4 solutions to test their extracellular biosynthesis of ZnO and Au NPs. The fungal filtrate became colorless and violet after mixing with Zn SO4 and HAuCl4. Only FI-03 is from 13 (FI-01 to FI-013). The most potent fungal strain for Zn O NP and Au NP nanoparticle synthesis was Fusarium Chlamydosporum. Pure, mostly spherical ZnO and Au NPs averaged 19.3 and 22.1 nm. UV-Vis absorption: Excitonic absorption peaks of ZnO NPs were between 300 and 400 nm. ZnO NPs' maximum absorption peak was 305 nm, while Au NPs' peak was 520 nm. One absorption peak indicates metallic gold nanoparticles. Au and ZnO NPs aggregate the most due to their hydrophilicity, HD of 34.88 and 15.77 nm, and PdI of 0.77, 1.00, and 0.952. Gold face-centered cubic fcc structure dominates Au NPs' XRD pattern. EDX shows 64.61 and 35.39 percent Zn and O, respectively, in both nanoparticles. The optical absorption band of gold nanocrystallites peaked at 2.2 keV in energy-dispersive X-rays.

Conclusion

Endophytic fungus biosynthesizes ZnO and Au NPs, which are bioactive compounds for medicine and food without toxic chemicals and are environmentally friendly.
Assessment of Improved Quality via the Adoption of Microbiology Automation
Authors: Lau J , Larsen J , Grys T , Rice F , Graf E
Published: November 2023

Introduction/Objective

Our laboratory implemented a full COPAN WASPLab microbiology automation line in March of 2023. Prior to this implementation, our laboratory routinely observed potential bacterial contamination of sterile specimens, as well as culture plates in which the specimens were not struck out, due to a large number of new staff members and heavy workloads. Both of these quality issues directly impact patient care due to potential misleading or delayed results. We hypothesized that automation of the plating and incubation steps would reduce both of these quality issues significantly.

Methods/Case Report

Potential contamination and plates not struck were self-reported by technologists during pre- implementation (July 2022-Feb 2023) and post-implementation (Mar-Apr 2023) periods. Potential contamination was defined as one or two colonies of bacteria on a single agar plate, consistent with skin fora, from a normally sterile source specimen and reviewed by the Director for potential clinical correlation. Plates unstruck in the post- implementation period continued to include those manually set up. A 2 two proportion z-test was performed to compare pre and post implementation data.

Results (if a Case Study enter NA)

A total of 3,055 and 1,750 sterile source cultures were analyzed in the pre- and post-implementation periods, respectively. Of these, 109 versus 8 were designated as potential contamination, respectively, resulting in a significant reduction (Z stat 6.7, p<0.0001). For the plate streaking portion, 22,814 and 7,211 cultures were analyzed in the pre- and post-implementation periods, respectively. Of these, 21 versus 3 plates were not struck, respectively, resulting in a greater than 2-fold reduction per culture, but did not meet significance.

Conclusion

Implementation of microbiology automation significantly reduced skin flora contamination of sterile source cultures. Proportions of unstruck plates were also reduced, although these did not meet significance, likely due to the low numbers.
Multiple Hepatic Microabscesses Caused by Magnusiomyces Clavatus in a Patient with Acute Myeloid Leukemia: A Case Report
Authors: Pokharel A , Elzieny M , Wey E , Zhang P L
Published: November 2023

Introduction/Objective

Invasive fungal infections can result in significant complications for acute myeloid leukemia (AML) patients undergoing induction chemotherapy. While Candida and Aspergillus are the most common fungal pathogens, Magnusiomyces clavatus (Geotrichum clavatum) is a rare fungal pathogen that has been reported to cause invasive infection in immunocompromised patients. Here, we report a case of fungemia and hepatic microabscess with Magnusiomyces clavatus in an 18-year-old female with AML.

Methods/Case Report

An 18-year-old female with AML in remission after induction chemotherapy presented with fevers. Further work-up revealed fungemia on her blood culture. While awaiting culture speciation, numerous hepatic lesions were identified on the abdominal CT scan, which were biopsied. The liver biopsy showed aggregates of fungi with septate hyphae on silver-stained sections. The initial morphologic differential diagnosis included Aspergillus and Mucormycosis. Her blood cultures ultimately revealed fungemia with Magnusiomyces clavatus (Geotrichum clavatum), a yeast that is rising in prevalence, particularly among neutropenic and leukemic patients. The morphology of fungi detected in the liver biopsy resembled Magnusiomyces clavatus and a subsequent PCR testing confirmed that the fungi present was Magnusiomyces clavatus. She was started on voriconazole and liposomal amphotericin B. She became afebrile with no growth on blood cultures for several days and was discharged to outpatient follow-up.

Results (if a Case Study enter NA)

N/A

Conclusion

This case highlights the clinical significance of Magnusiomyces clavatus in immunocompromised patients, particularly those with AML, and emphasizes the importance of considering rare fungal pathogens in such patients who present with fever. Treatment with voriconazole and liposomal amphotericin B can be helpful in relieving symptoms.
From research genomics to clinical genetics: Insourcing next generation sequencing in a pediatric and women’s hospital
Authors: Asinas J M
Published: November 2023

Introduction/Objective

The Sidra Medicine Clinical Genomics Laboratory (CGL) offers rapid and cost-effective next- generation sequencing (NGS) solutions such as Whole Genome Sequencing (WGS) and Whole Exome Sequencing (WES) which support various research initiatives in Qatar. With the current worldwide trend in precision and personalized medicine, the Pathology Genetics (PG) division is required to provide in-house diagnostic genetic testing to clinical patient groups. The main objective of this quality initiative project is to decrease the cost of NGS send-out tests and to perform patient testing in-house. The CGL NGS workflow and processes must be validated to comply with the clinical accreditation requirements of the College of American Pathologists (CAP).

Methods/Case Report

Assay performance metrics are considered for the validation of the Illumina NovaSeq 6000 NGS platform. Sample library preparation is performed in PG while sequencing and data analysis is based in CGL. NGS quality assurance in CGL involves the use of Illumina PhiX control mixed with the pooled library. To maintain the high throughput and low-cost NGS approach, Illumina S4 flow cells are used with efficient library pooling techniques. The TAT of clinical samples for WES and WGS analysis in CGL is around 14 days which includes sequencing, data conversion, and bioinformatics.

Results (if a Case Study enter NA)

A Service Level Agreement (SLA) between Sidra Research and Sidra Pathology was created to define the workflow and services provided by both departments with clear lines of responsibility and accountability. A quality manual is also written to describe the QMS of the genomics laboratory and outlines the various NGS services offered. CGL protocols are transferred to CAP-approved SOP templates for standardization with pathology documentation. For quality improvement, the NGS workflow in CGL is continuously developed to improve the data produced and TAT.

Conclusion

The collaboration between the two departments maximized the available infrastructures of Sidra Medicine, saved costly send-out tests, improved the TAT of genetic analysis, and most importantly enhanced healthcare outcomes and related clinical diagnostics in alignment with the National Health Strategy (NHS) of the country. Accreditation propels good QMS in laboratory services hence this quality initiative fulfills Sidra Medicine’s vision to provide total precision diagnosis and personalized medicine leading to the delivery of exceptional care to rank amongst the top medical centers internationally.
Development of a Companion Diagnostic for a Targeted Protein Degradation Therapy: Ultrasensitive and Minimally-Invasive Detection of SALL4 Oncoproteins for Therapeutic Monitoring
Authors: Liu J , Senussi Y , Melkonian A , Walt D R , Chai L
Published: November 2023

Introduction/Objective

Spalt-Like Transcription Factor 4 (SALL4), a member of the SALL family, is a regulator of embryonic stem cell development that plays a crucial role in cell renewal and proliferation. SALL4 expression is normally repressed in most adult organs but is reactivated in a multitude of cancers and upon treatment with hypomethylating agents (HMA). Research in the past 20 years established SALL4 as a novel, druggable cancer target. SALL4 targeting therapies (inhibitors and degraders) are under pre-clinical development. There are currently no FDA/CLIA approved SALL4 diagnostic tests beyond tissue immunohistochemistry (IHC). Therefore, there is outstanding clinical need for the development and validation of a less invasive and sufficiently-sensitive SALL4 expression assay which can be used for selecting, and monitoring patients on SALL4-targeting therapy such as molecular glue degraders, as well as monitoring patients on HMA treatment.

Methods/Case Report

Using the Simoa (Single Molecule Array) platform, a bead-based digital enzyme-linked immunosorbent assay, we cross-tested 5 commercial SALL4 antibodies and 13 antibody pair combinations, using the best antibody pair to test the matrix effects of human plasma, buffy coats, and bone marrow aspirates. For quantitative assay development, we successfully expressed and purified full-length SALL4 which will be used to calibrate the standard curve and determine the assay’s limit of quantification.

Results (if a Case Study enter NA)

The best antibody pair can detect both SALL4A and SALL4B isoforms, with stronger signal detected with the SALL4A isoform. We successfully optimized detection of SALL4 in bone marrow and peripheral blood matrix, and tested the utility of the assay for quantifying the efficacy of SALL4 degrader drugs and with hypomethylating agent treatment, using cell culture system. We also optimized multiple pre-analytic steps, including our cell lysis protocol, isolation of buffy coats using density gradient separation, and sample collection method comparison.

Conclusion

We developed an ultrasensitive SALL4 expression assay will be useful for monitoring patients on HMA treatment and SALL4-targeting therapy such as molecular glue degraders. There is ongoing effort to use MGB Biobank peripheral blood samples to validate SALL4 Simoa for patients with myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and liver cancer.
Diagnostic Value of Concurrent Endoscopic Ultrasound-Guided Fine-Needle Aspiration and Fine-Needle Core Biopsy in Cytology Categories of Pancreatic Solid Lesions: An Institutional Experience
Authors: Mousavi S , Mirzaei Baboli K , Salehiazar S , Rector A R
Published: November 2023

Introduction/Objective

Endoscopic ultrasound is the current standard of care in the evaluation of pancreatic solid lesions. Two methods have been employed in obtaining EUS-guided pancreatic specimens; fine needle aspiration (EUS-FNA) and fine needle core biopsy (EUS-FNB). EUS-FNA may have certain limitations, including the inability to assess the histological architecture and a limited sample size for immunohistochemical staining on cell blocks. EUS- FNB, which employs a larger needle for core biopsy, was developed to address these limitations. However, it is still uncertain which method is better suited for specific lesions. In this study, we evaluated the diagnostic efficacy of concurrent EUS-FNA and EUS-FNB from pancreatic solid lesions.

Methods/Case Report

We reviewed our institutional database for cases that had EUS-FNA from pancreatic solid lesions with a subsequent definitive diagnosis on histology. Similarly, the concurrent EUS-FNB findings were recorded. The cases were categorized based on the World Health Organization pancreaticobiliary cytology reporting system. Furthermore, the absolute risk of malignancy (ARM) of each diagnostic category (defined as the presence of high-grade dysplasia or worse on the histologic follow-up) was calculated.

Results (if a Case Study enter NA)

A total of 108 cases were reviewed for the study from 1/1/2019 to 6/1/2022. The patients were 47% male and 53% female with an average age of 68. No case was categorized as non-diagnostic or neoplastic high-grade. There were 20 benign, 7 atypical, 3 neoplastic low-grade, 6 suspicious for malignancy, and 72 malignant cases, and the associated ARM related to each category was 40%, 86%, 33%, 33%, and 96% respectively. Concurrent EUS-FNB was performed in 23 cases in total (12 in malignant and 11 in other categories). EUS-FNB exhibited 95% positive and 100% negative predictive values (PPV and NPV) in all categories combined and 89% PPV and 100% NPV in non-malignant and indeterminate categories (categories II, III, IV, VI) for correlating to the histologic follow-up.

Conclusion

Cases diagnosed in all categories except the malignant category demonstrated ARM rates higher than expected. When approaching a solid pancreatic lesion, EUS-FNB may increase the diagnostic value, especially in cases of non-malignant and indeterminate categories. Moreover, categorizing the cases in the benign category may require additional supporting data, and placing them in the nondiagnostic category may be more appropriate warranting re-sampling if there is a clinical vs pathologic discrepancy.