bluuebunny/crossref_metadata_2025 huggingface dataset:
The Utility of PathElective.com as a Curricular Adjunct in Laboratory Medicine Education
Authors: Lilley C M , Marin M J , Wiencek J , Fu L , Wolniak K , Kanakis C E , Hermelin D , Scordino T , Thomas C , Mirza K M , Demas C
Published: October 2021

Introduction/Objective

PathElective.com was founded as a means of combating stagnating resident and medical student education due to halting of in-person educational activities during the COVID-19 pandemic. The site has since grown to be included in medical student and resident training programs at numerous institutions across the world, serving as a unique means of delivering high-quality and trackable laboratory medicine education.

Methods/Case Report

The PathElective website was developed using Squarespace, video lectures were recorded by each professor or sourced from openly available web resources incorporating virtual slides, reading assignments, or relevant podcasts at the course director’s discretion. Monthly website traffic data were obtained through Squarespace analytics for the first 11 months of the website being available (May 1, 2020, to April 22, 2021). Geographic and source data were obtained through deidentified IP address analysis built-in to Squarespace analytics. Students who registered to take the online courses were assessed before and after interacting with the course materials using a dual form crossover quiz design to prevent memorization of questions and assess comprehension. Quiz data were all anonymous and improvement was determined using a paired t-test. Comparisons between courses were made via percentage improvements.

Results (if a Case Study enter NA)

Over the tracking period, PathElective.com received 352,012 page views, 73,550 visits, 33,225 unique visitors, and accrued 5,815 registered users. Most of the visitors (72.8%) arrived at the site via a direct URL input, 14.9% through a search engine, and 10.6% through social media. Most visitors were from the US (43.8%) or India (11.9%). With a total of 1598 test pairs being analyzed from all clinical pathology modules, the average increase in score was 14.4% (95%, CI=10.3-18.6, p=0.0052). All courses experienced a statistically significant increase in scores except for Clinical Chemistry lesson 3.2 (7%, -1.8-15.9% CI, p=0.12). Courses were well received with a median satisfaction score was very satisfied in all six assessment categories.

Conclusion

PathElective.com is a free and effective means of enhancing clinical pathology training in medical education. Students liked the online format, the quality of the lectures, and course faculty, and felt they could get help if needed. An area of improvement for this platform would be the interaction with students on social media.
Cytologic Analysis of a Glomus Tumor in the Left Second Toe: Case Report
Authors: Hwang J , McDowell S , Cole B , Huber A R , Reyes C
Published: October 2021

Introduction/Objective

Glomus bodies reside in the stratum reticularis of the dermis as well as in visceral organs. Their functions involve temperature and blood pressure regulation. The incidence of glomus tumors is approximately 1.5%, occur more frequently in women, and generally manifest during the third to fifth decade of life. A majority of glomus tumors are diagnosed by biopsy and excision. At least 19 case reports exist in the literature where glomus tumors are diagnosed by fine-needle aspiration (FNA). We add to this growing literature by discussing a case report involving the cytologic findings of an FNA-diagnosed glomus tumor.

Methods/Case Report

A 66-year-old female presented with left second toe pain for 41 years but worsening in the past several months. Physical exam revealed 5/5 muscle strength in her toes without loss of sensation. There was no edema, erythema, nor ecchymosis. Pain was notably out of proportion when palpating her second nailbed. Magnetic resonance imaging (MRI) with contrast was performed revealing a 1.1 x 1.0 x 0.9 cm circumscribed, ovoid mass involving the dorsal aspect of the second toe distal phalanx along its dorsal margin (Figure 1). The patient underwent fine needle aspiration and biopsy. Cytologic findings included clusters of uniform cells with round to oval nuclei and scant cytoplasm. There was spindling of cells noted in some of the clusters. Cells were surrounded by thick wisps of magenta colored myxoid material reminiscent of a pleomorphic adenoma (Figure 2). Biopsy showed uniform cells surrounding capillaries. Immunohistochemistry performed on the biopsy showed that lesional cells were positive for alpha-smooth muscle actin (SMA). A diagnosis of glomus tumor was made. Amputation was performed with clear margins.

Results (if a Case Study enter NA)

NA

Conclusion

Glomus tumor is a rare tumor that is usually diagnosed on biopsy; however, it has distinct cytologic features that can aid in its diagnosis on fine needle aspirations.
Fine-needle aspiration (FNA) of an abdominal wall mass malakoplakia mimicking malignancy: a case report
Authors: Alkashash A M , Segura S
Published: October 2021

Introduction/Objective

Malakoplakia is a granulomatous disease of infectious etiology that affects immunosuppressed individuals. It commonly involves the genitourinary tract, but the involvement of other systems and organs has been reported. Gram-negative bacterial infections are mostly the responsible agent, with Escherichia coli found in approximately 80% of cases. Malakoplakia can present clinically and radiologically as a malignancy.

Methods/Case Report

We present a case of a 16-year-old male with a history of acute liver failure requiring liver transplantation due to autoimmune hepatitis. He was admitted with concerns for rejection, and he was found to have an abdominal wall mass. MRI studies showed a lobulated, solid, and cystic mass measuring 11.0 x 4.9 x 1.9 cm in the right abdominal wall. The mass was extending through all the layers of the abdominal wall and protruding into the abdominal cavity with mass effect on the liver, encasing the common bile duct, hepatic artery and main portal vein, concerning for malignancy, versus a possible infectious process. Ultrasound-guided FNA and biopsy were performed. The Diff-Quik and Papanicolaou-stained smears showed abundant foamy macrophages with numerous granular intra- and extracellular slightly refractile inclusions (4-10 um), rare multinucleated giant cells, and fibroblasts. A Von Kossa stain highlighted the targetoid inclusions consistent with Michaelis-Gutman bodies. Additional stains were performed on the core needle biopsy, and the histiocytes were positive for CD68 and CD163. Stains for keratins, CD45, HSA, CD1A, and Langerin were negative. No acid-fast or fungal microorganisms were identified on AFB and GMS stains, respectively. The final diagnosis was malakoplakia, with no evidence of malignancy.

Results (if a Case Study enter NA)

NA

Conclusion

Fine-needle aspiration cytology is useful in establishing a fast diagnosis of malakoplakia and excluding malignancies.
Cytomorphologic findings of thyroid carcinoma showing thymus-like (CASTLE) differentiation: A case report
Authors: Abu-Salah A K , Segura S , Mesa H , Cramer H M
Published: October 2021

Introduction/Objective

Thyroid carcinoma showing thymus-like differentiation also known as intrathyroidal thymic carcinoma is a rare thyroid neoplasm arising from either an ectopic intrathyroidal thymic tissue or from remnants of thymobranchial pouches. On fine needle aspiration (FNA) its diagnosis can be challenging due to overlapping morphologic features with other aggressive thyroid carcinomas.

Methods/Case Report

A 31-year-old female consulted for 6-month history of neck swelling and tenderness. Thyroid ultrasound demonstrated a 2.6 x 2.5 x 2.1 cm nodule in the right lobe with punctate calcifications. FNA showed cellular smears composed of loosely cohesive and single basaloid neoplastic cells exhibiting significant cellular and nuclear pleomorphism. Focal squamous differentiation with keratinization was noted on the cell block sections. Immunocytochemical stains showed that the tumor was positive for cytokeratin AE1/AE3, p40, p63, CD117 and CD5 consistent with intrathyroidal thymic carcinoma. The Ki67 proliferative index was approximately 40%. A right thyroidectomy with central neck dissection confirmed the diagnosis and showed a 3.0 cm tumor with invasion into skeletal muscle, lymphovascular invasion and positive lymph nodes. The patient completed adjuvant radiotherapy and remain in remission at 3-months follow-up.

Results (if a Case Study enter NA)

NA

Conclusion

Intrathyroidal thymic carcinoma is a rare thyroid neoplasm that frequently shows squamous differentiation and therefore overlaps with papillary thyroid carcinoma with squamous morulae, squamous cell carcinoma and anaplastic carcinoma. The coexpression of squamous markers together with CD5 and CD117 allows the recognition of CASTLE on FNA samples.
Microsatellite unstable esophageal adenocarcinoma masquerading as a conventional esophageal primary
Authors: Jayaratne N , Reese A , Jiang K
Published: October 2021

Introduction/Objective

Patients with microsatellite instability (MSI) are susceptible to developing epithelial malignancies in multiple organs and systems, especially along the gastrointestinal tract. It’s important to know that MSI-tumors may present with an intriguing non-classical, “non-MSI-appearing”, histomorphology that deviates from the well-known MSI or Lynch syndrome spectrum. Pathologists should thus be prepared for unusual histopathological presentations in order to detect MSI and related therapeutic and prognostic targets. Ultimately, a timely and accurate classification is a crucial step in guiding clinical course.

Methods/Case Report

An 80-year-old male presented to an outside facility due to worsening dysphagia. Imaging and endoscopy studies confirmed a near-obstructing distal esophageal mass. Subsequently, an esophagogastrostomy was performed, which removed a moderately differentiated adenocarcinoma (pT3N1). The patient was managed with conventional chemotherapy after the surgery; however, due to progressive metastasis involving the liver, he was referred to our cancer center.

Results (if a Case Study enter NA)

Upon review of outside pathology materials, the tumor displayed irregularly arranged bizarre glands with eosinophilic cytoplasm and unusually large nuclei within the abundant fibrotic stroma. No intra-tumoral lymphocytes or “Crohn’s-like” pushing borders were identified. However, ancillary tests performed on acquired outside material showed loss of MLH1 and PMS2 with retained MSH2 and MSH6 in the tumor. Subsequent mutational analysis revealed additional MSI-related carcinogenic mutations. Accordingly, the previous regimen was switched to immunotherapy-based management. The patient remains disease-free 10-months later.

Conclusion

This unusual MSI esophageal adenocarcinoma exemplifies that such tumors may present with non- MSI/non-lynch histomorphology and that ancillary analyses should be carried out without reservation to evaluate microsatellite status. Thus, optimizing patient management and outcome.
Invasive Large Duct Type Pancreatic Adenocarcinoma: A Diagnostically Challenging Entity
Authors: Al-Attar M M , Khedr S M
Published: October 2021

Introduction/Objective

Large duct type invasive pancreatic adenocarcinoma is a morphological variant of pancreatic ductal adenocarcinoma that poses a radiologic and pathologic diagnostic challenge as it closely mimics other non- invasive neoplasms, including mucinous cystic neoplasms and intraductal papillary mucinous neoplasms (IPMN). We report a case of large duct type invasive adenocarcinoma that on radiology closely mimics an IPMN.

Methods/Case Report

The case id that of a 73-year-old male presenting with weight loss and chronic diarrhea. Abdominal imaging revealed features suggestive of main duct IPMN with possible side branch extension into the pancreatic head. Endoscopic retrograde cholangiopancreatography showed a bile duct stricture that was stented and biopsied, revealing mucinous material with neoplastic cells. A Whipple procedure was performed, revealing a 3.3 cm, tank-pink, papillary lesion in the pancreatic head, that is partially cystic with mucinous contents, and displaying exophytic extension into the main pancreatic duct.

Microscopically, the lesion consists of a high-grade IPMN involving the main pancreatic duct with side branch extension, and associated with invasive adenocarcinoma, the majority of which is of the large duct type, showing irregularly distributed large ducts with jagged edges and surrounding desmoplasia, with intra-luminal mucinous material and neutrophils. The lining cells show focal pseudo-stratification and bland cytology. Foci of conventional type invasive adenocarcinoma, clusters of invasive tumor cells, and peri-neural invasion are also identified. Post- procedure, the patient underwent chemotherapy with marked symptomatic improvement.

Results (if a Case Study enter NA)

NA

Conclusion

Large duct type invasive adenocarcinoma of the pancreas can closely mimic non-invasive pancreatic neoplasms, posing diagnostic challenges that require identification of subtle features to achieve the correct diagnosis and guide treatment.
Iso-chromosome 12p Analysis by Fluorescent In-Situ Hybridization: An Academic Institutional Experience
Authors: Patwardhan P P , Satturwar S , Dhir R , Quiroga-Garza G M
Published: October 2021

Introduction/Objective

Chromosome 12 abnormalities like iso-chromosome 12p (i12p) and amplification of 12p are seen in majority (89%) of the primary and metastatic testicular germ cell tumors (TGCTs). i12p can be detected by karyotyping, fluorescent in-situ hybridization (FISH) or reverse transcriptase polymerase chain reaction. The aim of this study was to review i12p FISH data at our institution and assess the clinical utility.

Methods/Case Report

Laboratory information system was queried over a period of 15 years to search for cases where i12p FISH test was requested. FISH test was performed using TelVysion 12p telomeric probe and CEP 12 centromere probe on paraffin-embedded tissue or cell blocks. A ratio of 12ptel/CEP12 signal of 1.4 or greater was considered as positive. Patient demographics, clinical presentation, pathologic findings, and follow-up data were documented and correlated.

Results (if a Case Study enter NA)

Total 58 cases were identified with an age range of 14 to 76 years. Majority were male (M=52, F=6). Of these cases, 15 were testicular and 43 extra-testicular cases that included resection (n=35), biopsy (n=20) and cell-blocks (n=3). i12p was detected in 8 out of 15 testicular cases while i12p was detected in 16 out of the 43 extra-testicular cases. The extra- testicular cases included 17 retroperitoneal lesions, 8 lesions from the mediastinum, 6 lymph nodes from other sites and 12 miscellaneous lesions. Using pathology diagnosis with immunohistochemistry as gold standard, overall sensitivity was 60% and specificity was 86%. There were 3 false positive cases [Benign testicular parenchyma (n=1), suspicious for germ cell neoplasia in-situ (n=1) and undifferentiated epithelioid neoplasm (n=1)].

Conclusion

Our results show that although the sensitivity was limited, FISH test for i12p demonstrated high specificity(86%) for diagnosis of primary or metastatic TGCTs. As an adjunct test, i12p FISH can help identify and further characterize a significant number of GCTs with unusual morphology or clinical presentation.
Malignant Glomus Tumor of the Kidney: A Case Report and Review of the Literature
Authors: Nwanze J , Shih J , Rolf N , Halat S K
Published: October 2021

Introduction/Objective

Glomus tumors are rare neoplasms arising from the glomus body which is a specialized arteriovenous anastomosis that has a role in temperature regulation of the skin. They account for less than 2% of soft tissue tumors and typically manifest as painful nodules in the extremities, most commonly in the subungual region of the fingers and dermis of the wrist, forearm, and foot. They rarely arise in visceral organs as they lack glomus bodies. There are rare case reports of benign glomus tumors arising in the kidney, and malignant renal glomus tumors are exceedingly rare.

Methods/Case Report

We present a case of a 32-year-old man who was found to have a right renal mass incidentally after being involved in a motor vehicle accident. Computed tomography of the abdomen revealed a 5.3 cm enhancing mass in the posterior aspect of the inferior pole of the right kidney. Histological examination revealed a solid neoplasm composed of a pleomorphic population of cells with densely eosinophilic to pale cytoplasm, centrally located round to oval nuclei with fine nuclear chromatin and relatively inconspicuous nucleoli. Prominent lymphovascular invasion and 1 mitotic figure per 10 high power fields were also present. Areas composed of necrosis, sclerosis, hemosiderin deposition and calcification were identified. Immunohistochemical stains revealed the neoplastic cells to be positive for CD34, vimentin, smooth muscle actin, caldesmon, with focal reticulin staining around the tumor cells. Cells were negative for desmin, high and low molecular weight cytokeratins, synaptophysin, chromogranin, PAX8, and GATA3. The morphology and immunoprofile of the mass are consistent with the diagnosis of glomus tumor.

Results (if a Case Study enter NA)

NA

Conclusion

Although very rare, the presence of prominent vascular invasion, increased mitotic activity as well as necrosis are consistent with malignant behavior and support the classification as a malignant glomus tumor.
Adenoid cystic carcinoma of the female genital tract – Case series with review of literature
Authors: Bhele S , Crisi G , Hunt J
Published: October 2021

Introduction/Objective

Adenoid cystic carcinoma (ACC) of the female genital tract is rare and the published literature is sparse. In the vulva it is considered to arise from Bartholin’s gland whereas, in cervix it arises from the reserve cells. Although morphologically ACC of female genital tract is similar to its counterparts in salivary glands, the clinical behavior is different.

Methods/Case Report

We describe the clinicopathologic and immunohistochemical features of three cases of adenoid cystic carcinoma of female genital tract with review of literature. The age of our patients ranged from 48 to 75 years with tumors ranging from 1.9 to 3.9 cm. The tumor sites were vulva (2 cases) and cervix (1 case). Two of the 3 patients presented with mass lesions and one patient presented with postmenopausal bleeding. Microscopically, all tumors showed classic morphologic features with cribriform, tubular and solid patterns. On immunohistochemistry, CD117 was consistently reactive in all 3 cases. In addition, the ductal and myoepithelial cell population were highlighted by keratin cocktail and p63 respectively. P16 was diffuse and block-like positive in two cases (one vulvar and cervical ACC). High risk HPV (HPV 33) was detected in one case of vulvar ACC. Two patients underwent surgical excision while one patient was deemed unfit for surgical treatment. All 3 patients received radiation therapy. On follow- up that ranged from 17 to 76 months, one patient is alive without evidence of disease. One patient died of disease with local recurrence and lung metastasis. The other patient died of complications (radiation proctocolitis with colonic perforation).

Results (if a Case Study enter NA)

NA

Conclusion

Our cases highlight the aggressive behavior of adenoid cystic carcinoma in the female genital tract and the need for close follow-up. Also high risk HPV has been demonstrated in cervical ACC previously, but our series demonstrates high risk HPV association with vulvar ACC.
Sporadic Uterine Cervical Angiomyolipoma with Concurrent Endometrial Adenocarcinoma
Authors: Masoud M A , Wei E
Published: October 2021

Introduction/Objective

Angiomyolipoma is a benign mesenchymal neoplasm composed of variable admixture of thick dysmorphic blood vessels, smooth muscle cells, and fat cells that commonly arises in the kidney. It is strongly associated with tuberous sclerosis but it can also occur as sporadic. Extra renal angiomyolipomas have been reported with the liver being the most common location. Few cases of angiomyolipoma in the female genital have been reported where the uterus being the most common site. Uterine cervical angiomyolipoma has rarely been reported.

Methods/Case Report

We reported a case of 64-year-old white female with postmenopausal bleeding. Endometrial biopsy revealed endometrioid type endometrial adenocarcinoma. MRI showed endometrium was thickened, and the cervix was enlarged with disruption of the cervical fibrous stroma on the anterior surface concerning for cervical stromal invasion. Grossly, besides the polypoid mass that involved the endometrial cavity, there was a firm nodule with whorled cut surface noted on the anterior surface of the cervix.

Microscopic examination of the cervical nodule revealed a classic variant of angiomyolipoma with mature adipocytes, spindle shaped smooth myocytes and anomalous thick-walled blood vessels with hyalinization. The spindle cells were positive for smooth muscle actin and caldesmon. CD34 highlighted the thick walled blood vessels. The stain for HMB- 45 was negative in contrast to renal counterpart. These findings are consistent with cervical angiomyolipoma. In addition, there was endometrioid endometrial adenocarcinoma, FIGO grade 1, with microsatellite stable phenotype, with only superficial invasion of myometrium, without involvement of cervical stroma.

Results (if a Case Study enter NA)

NA

Conclusion

This is a rare and probably the only presentation of cervical angiomyolipoma concurrently occurring with endometrial adenocarcinoma. It is uncertain if these two disease entities have genetic or pathogenesis association. The imaging studies were very concerning for cervical stromal invasion or questionable cervical cancer with local invasion. Cervical angiomyolipomas, though, extremely rare, may also be included in dysfunctional uterine bleeding differential diagnosis.
Endometrial Adenocarcinoma Biopsies: Can Targeted Education Increase Reproducibility and Is It a Good Idea?
Authors: Petty D , Blankenship H , Beuerlein W , Naal T , Li W
Published: October 2021

Introduction/Objective

Assessing p53 mutation on biopsies could provide prognostic and therapeutic planning information, as it predicts worse outcomes for patients with endometrioid adenocarcinoma (EA). Immunohistochemistry (IHC) mutation pattern staining varies, easily causing misinterpretation. This study was designed to see if education clarifying staining issues would increase reproducibility, and if mutations detected in this setting were of prognostic import.

Methods/Case Report

p53 IHC on 46 FIGO grade 1 EA biopsies was scored by blinded participants. Education was provided regarding internal controls (IC), and common misinterpretations. The participants rescored to assess reproducibility. Outcome parameters (clinical stage [CS], progression free survival, higher FIGO grade on resection, and presence of mismatch repair mutations) were also assessed.

Results (if a Case Study enter NA)

25% of scores changed post-education. Intraclass correlation among raters was 0.29 pre and 0.43 post (from fair to moderate). Mutation status changed in 5 cases. 2/5 caught IC failure for 1 case. Post-participation surveys found 0 participants were previously familiar with “high wild type,” and 60% were unfamiliar with cytoplasmic staining pattern, the possibility for heterogeneity, and necessary ICs. Every participant agreed grading was easier following education. Out of 6 patients with high CS disease (IIIC-IV), none had p53 mutation. 2/11 cases with higher FIGO grade (2-3) on resection had mutation. One patient had recurrence with no detectable mutation. 15/46 patients had MMR results available. No p53 mutation was detected in those with a loss of MLH1 and PMS2 (n=8).

Conclusion

Education on IHC issues can increase reproducibility in scoring, though overall reproducibility on biopsies was still subpar. Mutation detected in this setting did not correlate with current outcome parameters. Given the possibility of heterogenous expression and difficulties interpreting edge effect and assessing ICs in scant specimens, p53 IHC on EA biopsies is not recommended.
Sinonasal teratocarcinosarcoma, A rare neoplasm; Case report and literature review
Authors: Waleed M , Murtaza F , Khan M , Khurram M S
Published: October 2021

Introduction/Objective

Sinonasal teratocarcinosarcoma (SNTCS) is an unusual neoplasm with high malignant potential. Histologically it consists of epithelial and mesenchymal constituents, with a combination of teratoma and carcinosarcoma. It primarily occurs in the nasal cavity and paranasal sinuses. This aggressive neoplasm has a high recurrence rate with a five-year survival of 30-50 percent. To this date, less than a hundred cases have been mentioned in the literature. Early diagnosis and management of the tumor can enhance the prognosis.

Methods/Case Report

We present to you a case of a 63-year-old woman presenting with epistaxis, nasal congestion, and blockage. The tumor was completely removed surgically and postoperative radiation therapy was given. Grossly the tumor was gray-white, with a solid texture. Postsurgical microscopic examination of the sections from different areas showed variegated appearance having a mix of teratoid; carcinomatous; sarcomatous and primitive neuroectodermal elements. Immunohistochemical staining revealed tumor cells expressing desmin, EMA, and cytokeratin. The follow-up examination was done after a year and showed no sign of recurrence.

Results (if a Case Study enter NA)

N/A

Conclusion

Because of the scarcity and mixed cell lines of this tumor pathological diagnosis of the neoplasm is hard. Since this neoplasm is highly malignant and locally aggressive proper identification and removal are necessary for improving morbidity as well as mortality.
An Unusual Hematologic Manifestation in a COVID-19 Patient Treated with COVID-19 Convalescent Plasma
Authors: Andrzejewski C , Chakraborty S R , Stoddart L , Johari V
Published: October 2021

Introduction/Objective

A subset of Chronic Lymphocytic Leukemia (CLL) patients with COVID-19 may manifest rapid elevations in lymphocyte counts and poor clinical outcomes. Here we report our observations regarding this unusual hematologic manifestation in a CLL patient after he experienced a COVID-19 convalescent plasma (CCP) transfusion reaction.

Methods/Case Report

56-year-old A Rh- male with stable, treatment-naive CLL (13q deletion positive) diagnosed three years prior was admitted for COVID-19 hypoxia. Before developing COVID-19, baseline white blood cell (WBC) count was stable (~ 64 K/ mm3). Due to worsening hypoxia he was treated with an ARh+ High Titer CCP unit, Remdesivir, tocilizumab, and dexamethasone. The Blood Bank was notified of a possible CCP reaction and performed its standard workup which was adjudicated to be a febrile TACO reaction. During this evaluation it was noted that the patient’s WBC count had initially decreased to 46 K/ mm3, but rose on HD 3, to 78.4 K/mm3 and by discharge on HD 10 had increased to 200 K/ mm3. Flow cytometry revealed a B cell CLL immunophenotype. Post discharge day (PDD) 6 he developed herpes zoster. On post-discharge day (PDD) 7 his WBC count was 124K/mm3. By PDD 77 his WBC count had returned to baseline (~50 K/mm3).

Results (if a Case Study enter NA)

NA

Conclusion

The pt’s initial drop in his WBC count followed by a gradual rise has been observed in patients with severe COVID-19 independent of CCP infusion. Lymphocytosis in a subset of CLL patients with COVID-19 has been reported (termed “COVID-19 Induced Lymphocytosis” (CIL)) and, in contrast to our patient with an improved outcome, has been associated with severe/fatal outcomes. Of note these other patients did not receive CCP. Mechanisms related to CIL are unknown. Such poor clinical outcomes heighten the need for further studies of CIL. The role of CCP in affecting this process, if any, also merits further clarification.
Utilisation of Deep Learning-Enabled Image Analysis for Detection and Enumeration of Plasmodial Forms in Red Cells
Authors: Hu K , Welch W , Pilichowska M , Bacsa D , Vandenhirtz J
Published: October 2021

Introduction/Objective

Objective: This work investigates utilisation of deep learning enabled peripheral blood smear image analysis for automated detection and enumeration of red cell parasites.

Methods/Case Report

Methods: Peripheral blood smear red cell images from 30 individuals identified as positive and/or negative for plasmodilum falciparum forms were used. Blood submitted to hematology laboratory for complete blood count was evaluated on Sysmex XN 3100 analyzer with routine peripheral blood slides performed on instrument associated SP50 stainer. Images of red cells obtained with Xfinity DX40 microscope mounted camera were subjected to classification using deep learning software (Cognex, ViDi Suite 4.1). The training of the classification tool was performed on 200 peripheral blood smear images divided in two dataset classes: normal/negative and abnormal/positive for plasmodia, 50% of training images represented positive data set. Performance of the developed model was tested on 300 images including 66% positive for plasmodia obtained from 20 patients. Enumeration of parasitic forms was performed for each case. Model performance was compared to expert hematopathology reviewer which was used as gold standard.

Results (if a Case Study enter NA)

Results: Overall, Cognex ViDi Suite 4.1 demonstrates the effectiveness in discriminating between images positive and negative for red cell plasmodial forms as well as enables parasite quantification. Following performance specifications were determined for parasite detection: sensitivity (0.969230769), specificity (0.99383217). High correlation coefficients (0.9961) between automatically detected parasites and ground truth, on both image level and patient level, demonstrate the practicality of our method.

Conclusion

Deep learning enabled image analysis of peripheral blood smears is a promising alternative to manual identification and enumeration of red cell plasmodial forms with performance comparable to expert hematopathology reviewer.
Valproic Acid Induced Thrombocytopenia and Dysmegakaryopoiesis in a Pediatric Patient
Authors: Langlie J , Huberman M , Akgun Y
Published: October 2021

Introduction/Objective

Valproic acid is a branched short chain fatty acid derivative that is used primarily to treat epilepsy as well as mood disorders, certain types of headaches, and neuropathic pain. It is commonly prescribed in the pediatric population and has shown to be effective for refractory epilepsy with adequate seizure control. Serious side effects may be prominent if the medication is not kept at the therapeutic range. A wide variety of known hematologic problems can be encountered including but not limited to anemia, thrombocytopenia, and leukopenia.

Methods/Case Report

We present a case of a pediatric patient with a past medical history significant for history of seizure disorder and who presented to Jackson Memorial Hospital for intermittent fevers and multiple unexplained bruises for 3 weeks as well as fatigue and weakness.The patient was recently started on valproic acid. Complete blood count (CBC) was obtained and showed a platelet count of 23 x10(3)/mcL with WBC of 3.5 x10(3)/mcL and hemoglobin of 9.7 g/dL.Serum valproate concentration was critically high (154 mg/L). Trephine biopsy showed a normocellular marrow (60%) showing maturing trilineage hematopoiesis and scattered atypical megakaryopoiesis characterized by small forms that are seen in relatively loose interstitial clusters (Figure 1). The marrow aspirate smears were characterized by cellular spicules with dysmegakaryopoiesis including numerous small hypolobated forms with frequent forms showing separated nuclei (Figure 2, 3, and 4). Blasts did not appear increased, comprising overall 1% of marrow cellularity. Karyotype studies revealed a normal female karyotype, 46, XX. FISH studies using probes commonly detected in MDS were negative. Next generation sequencing was negative for AML specific mutations including GATA1 and GATA2 mutations.

Results (if a Case Study enter NA)

N/A

Conclusion

This case report highlights the significant hematologic adverse effects of valproic acid, specifically pancytopenia with dysmegakaryopoiesis, raising the clinical suspicion of potential myelodysplastic syndrome. Critically high level of valproic acid (154 mg/L) and normalization of CBC after the stoppage of the medication strongly suggests that valproic acid can cause severe bone marrow suppression and specific morphologic atypia in the megakaryocytic lineage thus introducing a potential diagnostic pitfall. Because the CBC returned to normal, bone marrow biopsy was not repeated.
Essential Thrombocytosis and Hepatocellular Carcinoma: A Mechanistic Challenge
Authors: Mohammed S
Published: October 2021

Introduction/Objective

Thrombocytosis has been reported in 8.2% of patients with Hepatocellular carcinoma [HCC] and has been attributed to increased Thrombopoietin [TPO] production by the tumor.

Methods/Case Report

We present a case of a 68-year-old male with a history of Hepatitis C and ethanol abuse presented with complaints of headache and chills. Imaging studies revealed a large mass in the liver [right lobe] suggesting an HCC of fibrolamellar type. His platelet count [PC] was 965 K/mcL. The serum AFP [Alpha feto protein] concentration was >51,800 ng/ml. There was no evidence of metastatic disease and the patient was started on Capecitabine and radiation therapy targeting the liver mass. Lung metastasis became evident and Sorafenib was added. His PCs and AFP concentrations however continued decreasing to 306 K/mcL and 460.7 ng/ml respectively. His PC then increased to a peak of 1.32 million/mcL 10 months later. The molecular workup done at our reference lab was positive for CALR [Calreticulin] mutation. The patient was started on Hydroxyurea and his PC decreased to 323 K/mcL at the time of writing. His AFP has remained stable. This case illuminates the complicated relationship between HCC and thrombocytosis. The therapy directed against the HCC did decrease PC and AFP concentration in our case. The second wave of thrombocytosis led to the discovery of CALR mutation, and the patient was diagnosed with Essential Thrombocytosis [ET]. Treatment with Hydroxyurea again decreased the PC while AFP concentration was increased but stable. Thrombopoietin levels have remained stable for the patient after treatment with Hydroxyurea.

Results (if a Case Study enter NA)

NA

Conclusion

Although the question of which mechanism(or possibly both) was at work in this case cannot be resolved definitely, two points are worth noting. The first is that- the assumption that the thrombocytosis was related to the HCC delayed testing for mutations associated with Essential Thrombocytosis. The second is that the TPO assay that may have yielded useful information in sorting out the alternatives was not ordered early enough before starting hydroxyurea.
Carboxypeptidase A1 (CPA1) immunohistochemistry is highly sensitive and specific for acinar cell carcinoma (ACC) of the pancreas
Authors: Uhlig R , Clauditz T
Published: October 2021

Introduction/Objective

Introduction: Carboxypeptidase A1 (CPA1) is a zinc metalloprotease which is produced in pancreatic acinar cells and plays a role in cleaving C-terminal branched-chain and aromatic amino acids from dietary proteins. This study assessed the utility of immunohistochemical CPA1 staining for diagnosing pancreatic acinar cell carcinoma.

Methods/Case Report

Methods: A total of 15,680 tumor samples from 132 different tumor types and subtypes as well as 8 samples each of 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format.

Results (if a Case Study enter NA)

Results: CPA1 was strongly expressed in acinar cells of all normal pancreas samples but not in any other normal tissues. CPA1 immunostaining was detected in 100% of 11 pancreatic acinar cell carcinomas and one mixed acinar endocrine carcinoma (MAEC), but absent in 449 pancreatic ductal adenocarcinomas, 75 adenocarcinomas of the ampulla of Vater, and 11,739 other evaluable cancers from 128 different tumor entities. A weak to moderate diffuse staining of epithelial and stromal cells of cancer tissues immediately adjacent to non-neoplastic pancreatic acinar cells often occurred and was considered to be caused by diffusion of the highly abundant CPA1 from normal acinar cells that may have suffered some autolytic cell damage.

Conclusion

Our data show that CPA1 is a highly sensitive and largely specific marker for normal and neoplastic pancreatic acinar cells. CPA1 immunohistochemistry greatly facilitates the otherwise often difficult diagnosis of pancreatic acinar cell carcinoma.
A Retrospective Review of the Effect of COVID-19 Pandemic on Laboratory Utilization
Authors: Olayinka O , Odujoko O , Barasch S , Farley J , Woodruff C , Chan S
Published: October 2021

Introduction/Objective

We performed a retrospective analysis of test volumes in clinical pathology prior to and during the COVID-19 pandemic to better understand the impact of the pandemic on our laboratory utilization.

Methods/Case Report

The laboratory information system was queried for test order volume in 2019 and 2020 using Discern Analytics 2.0. Representative tests including C-reactive protein (CRP), D-dimer, fibrinogen, ferritin, lactate dehydrogenase (LDH), procalcitonin, prothrombin time (PT), point of care iSTAT blood gas analysis, ABO and Rhesus typing (ABORh), antibody screening, flow cytometry, and serum protein electrophoresis (SPEP). Data was analyzed using Microsoft Excel 2013.

Results (if a Case Study enter NA)

The data showed an increase in the number of tests ordered and verified in the in-patient setting. The increase was most substantial for D-dimer, CRP and LDH with a percentage increase of approximately 200% on each test from year 2019 to 2020. An increase of 73% and 57% was noted for ferritin and fibrinogen respectively. A slight decrease in volume was noted for tests ordered in the out-patient setting including SPEPs during the pandemic. There was no significant change in the number of orders verified for point of care ISTAT blood gas testing between 2019 and 2020. Procalcitonin test volume increased steadily from its implementation in May 2020 with a steep rise in test volume in November and December. A total of 75,295 SARS-CoV-2 molecular tests were ordered between March and December 2020 with approximately 80% of the orders being performed as a send- out test.

Conclusion

The COVID-19 pandemic has had a substantial impact on laboratory utilization with significant volume increases in tests that guide the management of hospitalized COVID-19 patients and slight decrease in tests ordered mostly in the outpatient setting. These results may help guide current and future decisions relating to laboratory operations during pandemics.
Optimizing Run Control Performance in Tissue-Based Biomarker Testing: Experience of an Industry-Based CAP/CLIA Laboratory
Authors: Feng J D , Tozzi D , Liddell J , Gleason M , Pestic-Dragovich L , ElGabry E
Published: October 2021

Introduction/Objective

Introduction: In contrast to traditional labs, our CAP/CLIA Lab performs patient sample testing only for pharma-sponsored clinical trials. Very limited patient material is received, usually in the form of unstained slides rather than wet tissues. Strict run control (RC) quality measures are therefore essential to avoid repeat testing, exhaustion of patient material and/or delay of patient enrollment decisions. We describe methods to optimize RC staining performance and consistency.

Methods/Case Report

Methods: The RC failure rate was evaluated retrospectively and prospectively from January 2018 through March 2021. Specific failure modes were evaluated, including: 1) instrument-related (catastrophic mechanical failure, slide derailment, low temperature error), 2) stain-related (lighter or darker staining vs. reference), 3) tissue-related (tissue loss/fall-off). RC failures were also tracked by instrument and by individual biomarker.

Results (if a Case Study enter NA)

Results: 33,189 patient samples (84,130 slides) were tested from January 2018 through March 2021. Concurrently, 14,794 RC slides were tested across more than 115 biomarkers, including immunohistochemistry, multiplex immunofluorescence, and in situ hybridization assays. The RC failure rates by year were: 2018: 3.2 % (116 RCs), 2019: 3.8% (156 RCs), 2020: 1.9% (100 RCs), and 2021 (through March) 1.3% (21 RCs). The decrease in RC failure rate was a direct result of process changes addressing each of the failure modes, including, but not limited to: 1) improvement in slide storage conditions, 2) more selective RC tissue selection, and 3) more consistent interaction with on-site instrument support.

Conclusion

Process improvements addressing pre-analytic and analytic RC failure modes have resulted in a year-over-year decrease in RC failures. Consequently, our first-pass rates for immunohistochemical, immunofluorescence multiplex, and in-situ hybridization testing of patient samples have increased. Close monitoring of RC failure rates and near-real-time troubleshooting of individual RC failures are important components of successful operation in our unique laboratory setting, where patient material for testing is limited.
The Impact of Diversity and Conclusion on Employees’ Engagement Scores in The Laboratory
Authors: Abdelmonem M , Wasim H , Abdelmonem M
Published: October 2021

Introduction/Objective

Employee engagement is one of the most critical elements for the success of any organization. Proper engagement of the employees often leads to the success of an organization, while poor employee engagement often leads to the failure of an organization. Diversity is the presence of differences within an organization, such as differences in race, ethnicity, gender, sexual orientation, disability, or any other number of things. Inclusion is the practice of ensuring that people feel a sense of belonging and support from the organization.

Methods/Case Report

A retrospective study was performed at a mid-size hospital in California. The overall employee engagement score was recorded twelve months before and after founding a diversity and inclusion council. The diversity and inclusion council consisted of 12 members from all different races and gender, sexual orientations, disabilities, and socioeconomic status includes clinicians, administrators, and employees from all different hospital departments. On top of the 12 councils, nine Employee Resources Groups (ERG) represent minorities and underrepresented groups.

Results (if a Case Study enter NA)

The employee engagement score for 12 months (January 2019 to December 2019) for fully engaged employees was 29.5%, while the employee engagement score for 12 months (January 2020 to December 2020) for fully engaged employees was 49.3. The diversity and inclusion council was founded at the end of 2019. The data was obtained from the annual employee engagement survey.

Conclusion

There was a significant improvement (59.8%) in employee engagement score after launching the diversity and inclusion council. Diversity and inclusion promote the development and advancement of underrepresented groups in the laboratory through professional development courses and training. It actively creates a productive work environment within the laboratory that is free of harassment and bullying. Diversity and inclusion are vital for the laboratory to improve employee engagement scores, production, employees retentions, and laboratory financial performance.
Meeting clinical needs for and sidestepping supply chain threats to COVID-19 testing through continuous process improvement
Authors: Rice F , Yip T , Bolster LaSalle C , Graf E
Published: October 2021

Introduction/Objective

The first human case of SARS-CoV-2 infection was reported in December of 2019. By late February 2020 evidence of community transmission in the United States was documented and soon it developed into a global pandemic. On March 11, 2020, the Mayo Clinic Arizona’s Microbiology Laboratory introduced a PCR test for diagnosis of SARS-CoV-2 infection. Even as testing demands exponentially increased, the hospital relied on timely results to assist in directing patient care. In order to provide timely results in the face of continuously emerging supply chain threats, we needed to increase our capacity for SARS-CoV-2 PCR testing by reducing technologist time and reagent waste, without impacting turnaround time or other quality metrics such as repeat rate.

Methods/Case Report

Technologist time was measured in hands-on time per specimen. Reagent use was defined by the volume of lysis buffer (the primary rate limiting reagent due to supply chain constraints) used per sample. Turnaround time was measured from receipt in lab until result verification and the rerun rate is the percent of specimens with an internal control (IC) failure, an indicator of specimen or process quality. Unnecessary steps were determined using a process map, spaghetti diagram and waste walk. Improvements included simplifying steps, changes to protocols and lab design. Impacts of the improvements were measured for 5 months post-implementation.

Results (if a Case Study enter NA)

Process improvements reduced technologist time per sample by 30.8 seconds and decreased critical reagent needs by 23.6%. Improvements led to $104,000 in just reagent savings over 5 months. Turnaround time and rerun rates were not negatively impacted.

Conclusion

By creating the leanest possible workflow, we were able to meet the demands for accurate and timely SARS-CoV-2 results. In future workflows, we will continue to implement lean processes and ensure the most efficient use of limited resources.