bluuebunny/crossref_metadata_2025 huggingface dataset:
Unusual liver Involvement by Small Cell Carcinoma Arising in an Ovarian Malignant Mixed Mullerian Tumor
Authors: Jayaratne N , Pereira MD D , Jiang K
Published: November 2022

Introduction/Objective

Malignant mixed Mullerian tumor (MMMT) is a rare and aggressive tumor with patient survival of fewer than three years. MMMT harbors multilineage differentiation associated with malignant epithelial and stromal components. Awareness and familiarity with these characteristics are essential for patient stratification and clinical management.

Methods/Case Report

A 64-year-old female presented with refractory lower abdominal pain and bloating. Imaging studies revealed a 14-cm pelvic mass. The patient underwent urgent hysterectomy with salpingo-oophorectomy. She was diagnosed with ovarian MMMT(A) and received chemotherapy. The patient returned 2 months later with new- onset abdominal pain. CT detected numerous liver lesions; a biopsy was performed.

Results (if a Case Study enter NA)

The liver biopsy revealed metastatic small cell carcinoma (SCC[B], positive for synaptophysin and CD56; Ki67 >90%.). However, no concurrent lesions were identified on imaging. Further testing was attempted to locate the source of the SCC. Re-review of the MMMT with additional tissue sectioning identified sheets of high-grade pleomorphic malignant cells with a high N:C ratio, arranged in rosettes and without mucin. Additional immunohistochemistry labeled this MMMT diffusely with synaptophysin(C), chromogranin, and CD56. Furthermore, microscopic foci of MMMT showed higher grade histomorphology similar to the liver SCC which stained for PAX5(D). These findings illustrate a rare MMMT with a neuroendocrine carcinoma/SCC component which gave rise to liver metastasis.

Conclusion

This unusual liver SCC in a patient with prior MMMT exemplifies the multipotent malignant potential of MMMT and demonstrates the importance of having a spectrum of differentials and carrying out meticulous histomorphologic and ancillary analyses, especially when there is unusual histomorphology and discordance in clinical course.
Recurrent Small Bowel Obstruction and Perforation as a Complication of EFEMP1-Associated Systemic Venous Amyloidosis
Authors: Karimi S S , Ree N
Published: November 2022

Introduction/Objective

Amyloidogenic protein EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) is a newly described age-related systemic venous amyloidosis. EFEMP1 venous deposition has recently been reported in postmortem gastrointestinal specimens in which the deceased presented with gastrointestinal bleeding.

Methods/Case Report

We report a case of a 53-year-old female with long-standing seronegative spondylitis, and multiple recurrent small bowel obstructions and perforations status post surgical interventions who presented with 3 days of generalized abdominal pain, 10/10 in severity with nausea, emesis and absence of bowel movement. Abdominal CT scan confirmed closed loop obstruction in the left hemi-abdomen. An emergent partial duodenectomy was performed with extensive lysis of adhesion which revealed a perforated jejunal diverticulum with abscess formation. Microscopic examination demonstrated the presence of eosinophilic, amorphous, acellular material in the venules of the duodenum wall. Congo red stain demonstrating the presence of amyloid deposits and the specimen was sent for amyloid typing. Liquid chromatography tandem mass spectrometry demonstrated a peptide profile consisting of serum amyloid P, apolipoprotein A4, apolipoprotein E, and abundant peptides associated with EFEMP1/FBLN3 consistent with a recently described age-related venous amyloidosis derived from EFEMP1 protein.

Results (if a Case Study enter NA)

N/A.

Conclusion

EFEMP1-associated systemic venous amyloidosis has a predilection for females with a median age of 75 years and almost exclusively occurs in the gastrointestinal tract. We report this case for its novelty, unique clinical presentation and to emphasize awareness of this entity as we learn more about its etiology, presentation, management, and prognostication.
A Comparative Analysis of CPA1, bcl10 and Chymotrypsin for the Distinction of Pancreatic Acinar Cell Carcinomas
Authors: Uhlig R , Minner S , Luebke A , Weidemann S , Lebok P , Gorbokon N , Blessin N C , Lennartz M , Sauter G , Jacobsen F , Clauditz T S
Published: November 2022

Introduction/Objective

Introduction: Pancreatic acinar cell carcinoma (PACC) is a rare tumor of the pancreas with an intermediate prognosis as compared to pancreatic neuroendocrine tumors (PNE) and pancreatic ductal adenocarcinoma (PDAC) from which it may be difficult to distinguish by morphology alone.

Methods/Case Report

Methods: To study was the efficiency of immunohistochemical markers, 18 PACCs, 531 PDACs, 64 PNEs, 117 extra pancreatic neuroendocrine neoplasms (EPNN), 826 colorectal carcinomas (CRC) and 252 gastric carcinomas (GC) were analyzed with antibodies for CPA1 (MSVA-601M), bcl10 (Santa Cruz sc5273), and chymotrypsin (Biorad 2100-0657) in a tissue microarray format.

Results (if a Case Study enter NA)

Results: CPA1 was positive in 18 of 18 (100%) of PACCs, 0 of 49 (0%) of PNEs, 0 of 88 (0%) of EPNNs, 10 of 404 (2.5%) of CRCs, and 0 of 178 (0%) of GCs. Chymotrypsin was positive in 16 (87,5%) PACCs, 1 (2%) PNEs, 2 (2.3%) EPNNs, 10 (2.5%) CRCs, and 1 (0.6%) GCs. Bcl10 was positive in 18 (100%) PACCs, 2 (4.1%) PNEs, 5 (1%) EPNNs, 109 (27%) CRCs, and 18 (10%) GCs. These data resulted in a sensitivity and specificity of 100%/99.2% for CPA1, 100%/88.4% for bcl10, and 94.4%/98.6% for chymotrypsin.

Conclusion

CPA1 and chymotrypsin are both highly specific and sensitive for ACC while bcl10 is sensitive but has markedly lower specificity. Because all “false positive” cases identified by CPA1 were CRCs that only showed a positive staining in goblet cells and an identical staining pattern was observed in all these cases for chymotrypsin and bcl10, a pancreatic origin of the mucus in these goblet cells is concluded.
Benign Mullerian Glandular Inclusions in Men: A Metastatic Carcinoma Mimic
Authors: Bhatt M , Chand M , Qu H
Published: November 2022

Introduction/Objective

Benign mullerian glandular inclusions (MGI) in lymph nodes is a well documented finding in women. However, it can also very rarely occur in men and mimic metastatic carcinoma. To our knowledge, only seven cases of benign MGI in men have been reported in the literature.

Methods/Case Report

We here-in present a case of a 62-year-old male with a three-year history of prostatic adenocarcinoma Gleason score 6, initially diagnosed on needle core biopsies. Subsequently, the patient underwent a radical prostatectomy with bilateral pelvic lymph node dissection. Histological evaluation of the right pelvic lymph node demonstrated cystically dilated glands beneath the capsule composed of cuboidal to columnar cells with minimal atypia raising concern for metastatic carcinoma to the lymph node. Immunohistochemical (IHC) stains showed the glandular cells to be positive for estrogen, progesterone, PAX-8 and WT-1; while negative for calretinin and PSA immunostains. This IHC profile in conjunction with the morphological findings are consistent with the diagnosis of benign mullerian-type glandular inclusions within the lymph node.

Results (if a Case Study enter NA)

NA.

Conclusion

As benign MGI is a rare finding in men and can easily be mistaken for metastatic carcinoma, this case demonstrates that clinical awareness of this entity is essential to avoid wrongful diagnosis of metastatic carcinoma and unnecessary therapeutic treatment. Utilizing immunohistochemical stains to further characterize the glands is critical to obtain the correct diagnosis.
Every TURP Is not Just BPH
Authors: Al-kharouf I , Sami F , Hamza A
Published: November 2022

Introduction/Objective

Transurethral resection of prostate is a common specimen in surgical pathology practice. These specimens usually demonstrate benign prostatic hyperplasia. However, occasionally incidental prostate cancer is identified. Finding a true mesenchymal tumor in these specimens is exceedingly rare. We present a unique case of prostatic adenocarcinoma Gleason score 3 + 4 =7 and concurrent solitary fibrous tumor identified on a TURP specimen. Solitary fibrous tumor in this anatomical location is rare with approximately 50 cases reported in the English language literature.

Methods/Case Report

An 86-year-old male presented with symptoms and signs of urinary retention. On clinical evaluation the prostatae was profoundly enlarged with a calculated volume of 283cc; firm in consistency. He was given trial of medical management including finasteride, tamsulosin and Foley catheter placement. Subsequently, the patient underwent transurethral resection of prostate. Complete morcellation was not possible at the initial surgery due to hard consistency of the gland. Pathologic evaluation showed prostatic adenocarcinoma Gleason grade 3 + 4=Score 7 (Grade group 2) involving 10% of submitted tissue in addition to the changes of benign prostatic hyperplasia. Additionally, the background stroma demonstrated short plump oval to spindle cells with inconspicuous nucleoli and collagenous background, arranged in a haphazard (‘‘patternless’’) pattern. Immunohistochemical stains showed these lesional cells to be positive for STAT6 and CD34 and negative for desmin, S100, SOX-10, CD 117, DOG-1 and NKX 3.1. Morphology and immunohistochemical profile were compatible with solitary fibrous tumor involving the prostate. The patient is alive and symptom-free 9 months after the procedure.

Results (if a Case Study enter NA)

NA.

Conclusion

This case highlights the value of thorough evaluation of prostatic tissue in TURP specimens not only for prostate cancer but other tumors as well. It also reminds the practising pathologist to keep an eye out for the stromal lesions of the prostate gland. Also finding one lesion should not dissuade one from looking for additional concurrent lesions.
Hypertension in Young Adults: Think Juxtaglomerular Cell Tumor!
Authors: Quach P , Hamza A
Published: November 2022

Introduction/Objective

Juxtaglomerular cell tumor is a benign, renin-secreting neoplasm. The tumor arises from the juxtaglomerular apparatus cells of the kidney. Because the tumor is hormonally active, patients usually suffer from hypokalemia, hyperaldosteronism, and hypertension. The typical patient population is adolescents and young adults with slight female predominance. Herein, we describe a case of a 19-year-old Asian female with a somewhat atypical presentation.

Methods/Case Report

A 19-year-old Asian female presented with upper extremity weakness, numbness, and tingling. On physical examination, the only notable finding was hypertension. Extensive work up reveled an aldosterone level of 71 nanograms per deciliter and plasma renin activity of 6.25 nanograms per milliliter per hour. A CT scan of the abdomen revealed a 2.4cm mass in the lower pole of the left kidney. The mass was resected by partial nephrectomy. Sectioning of the specimen revealed a 2.4cm well-circumscribed, encapsulated tumor. On microscopic evaluation, the tumor had glomoid appearance with sheets of uniform, round to polygonal cells with clear to eosinophilic cytoplasm. The stroma was scanty, mitoses were rare, and necrosis was not identified. Immunohistochemical stains showed the tumor cells to be positive for CD117, CD34, Cathepsin K, Synaptophysin, and CD10 and negative for ER, PR, CK7, PAX-8, pancytokeratin, EMA, S100, Melan-A, HMB45, SMA and CAIX. Diagnosis of Juxtaglomerular cell tumor was rendered. The patient was alive and well and without signs of recurrence 14 months after surgery.

Results (if a Case Study enter NA)

NA.

Conclusion

This case highlights the importance of a regular physical exam and having a high index of suspicion in patients presenting with unusual complaints.
Rhabdoid Melanoma Solitary Metastasis to Kidney with Renal Vein Invasion Mimicking Renal Cell Carcinoma
Authors: Halat S K , Singh A , Bach K
Published: November 2022

Introduction/Objective

83 percent of malignant melanoma cases present as localized skin lesions. However, a small percentage of patients present with concurrent metastatic disease or experience late metastasis. Metastatic melanoma has highly variable presentation and morphology, frequently mimicking other tumors. The most common metastatic sites in order of frequency are skin and subcutaneous tissue, lungs, liver, bones, and brain. While rare, metastasis to the kidney can occur and typically takes the form of multiple micrometastases.

Methods/Case Report

Here we present an unusual case of a late, purely rhabdoid large solitary renal metastatic melanoma with renal vein invasion, mimicking rhabdoid renal cell carcinoma. The patient is an 84 year old male with a remote history (30 years) of cutaneous malignant melanoma who was referred with a CT scan demonstrating 7.9 x 5.7 x 5.7 mass in the lower pole of the left kidney with a tumor thrombus in the renal vein hhighly suspicious radiographically for renal cell carcinoma. The patient underwent a radical nephrectomy. Macroscopically there was a solitary 7.7 x 6.3 x 5.5 cm tan-grey mass in the lower pole with gross invasion into the renal sinus fat and renal vein resembling the macroscopic appearance of a renal cell carcinoma. Microscopic examination demonstrated pleomorphic tumor cells with pure rhabdoid morphology, extensive necrosis and Lymphovascular invasion. No pigment was identified. No classic clear cell areas were identified. Immunohistochemical stains were positive for S100, SOX10 Melan-A, HMB45 and vimentin and negative for AE1/3, CK7, CAIX, PAX8, P63, CD117 and AMACR. Multiple resected lymph nodes were negative for metastasis

Results (if a Case Study enter NA)

NA.

Conclusion

This case is a rare and unusual presentation of melanoma, and it’s important to keep this diagnosis in consideration in the setting of unusual morphology of renal tumors.
Correlation Between hr-HPV Genotypes/Negative Cytology with Cervical Histology Findings
Authors: Benchbani H , Hamidpour S
Published: November 2022

Introduction/Objective

It is well established that the persistent of hr-HPV infection is necessary for the development of cervical dysplasia. Currently, routine cervical cancer screening include both high-risk human papilloma virus (hr- HPV) testing and cervical cytology tests. The guidelines for managing HPV-positive/cytology-negative results is cotesting at 1 year, and/or immediate colposcopy if HPV16 and/or HPV18 is positive. We analyzed the correlation between hr-HPV genotypes /negative cytology with cervical histology findings.

Methods/Case Report

Retrospective chart review was performed to identify all negative pap smears with positive hr-HPV and follow up colposcopy for patients who presented to our institution from January 2018 to December 2019. We calculated the distribution of HPV genotypes within low grade and high-grade cervical lesions among patients with HPV-positive/cytology-negative pap smears.

Results (if a Case Study enter NA)

179 patients with HPV-positive/cytology-negative pap smears were included. The age range was 22-69 years old. Among these patients, 6.70% had low-grade squamous intraepithelial lesion (LGSIL) and 6.14% had high-grade squamous intraepithelial lesion (HSIL) on follow up biopsy. The detection rates of HPV genotypes among patients with LGSIL diagnosis were HPV16 (41.66%), HPV18 (16.66%) and other hr-HPV (41.66%). The detection rates of HPV genotypes among patients with HGSIL diagnosis were HPV16 (9.09), HPV18 (0%), other hr-HPV (72.72%), combined HPV16 + other hr-HPV (9.09), combined HPV18+ other hr-HPV (9.09%).

Conclusion

According to our data, patients with negative cytology and HGSIL on biopsy have higher association with other hr-HPV (not 16 or 18) than HPV 16 and 18. Patients with negative cytology and LGSIL on biopsy have higher association with HPV16 and other hr-HPV subtypes than HPV18. Thus, we recommend follow-up colposcopy even for patients with other hr-HPV infection.
Uterine Leiomyoma with Bizarre Nuclear Morphology: Report of a Rare Case
Authors: Hosseini H , Al-Refai R , Morrar D , Unger P , O'Leary X , Villella J A
Published: November 2022

Introduction/Objective

Sporadic fumarate hydratase (FH)-deficient leiomyoma occurs as a result of somatic inactivation of the FH gene and has been found to represent 1% of uterine leiomyomas. Germline inactivation of the FH gene is associated with a rare autosomal dominant syndrome known as hereditary leiomyomatosis and renal cell carcinoma (HLRCC). Women with HLRCC develop cutaneous and uterine leiomyomas and an aggressive renal cell carcinoma, with 57% reported to undergo hysterectomy at 30 years of age or younger. All FH-deficient leiomyomas display a distinct histology characterized by scattered bizarre nuclei, eosinophilic cytoplasmic inclusions, conspicuous eosinophilic nucleoli, and perinuclear clearing. Immunohistochemically, the neoplastic cells do not express FH while they are positive for S-(2-succino)-cysteine (2SC), a metabolite that accumulates when FH is inactivated.

Methods/Case Report

We present a 48-year-old woman who underwent supracervical hysterectomy for a symptomatic uterine leiomyoma. She was status post left salpingo-oophorectomy for left adnexal endometriosis. Grossly, the hysterectomy specimen was significant for one 8.0 cm intramural uterine corpus tumor with a tan-white whorled cut surface. Histology showed a smooth muscle neoplasm in the myometrium composed of spindled cells with abundant eosinophilic cytoplasm, occasional enlarged prominent nucleoli with perinuclear halos, intracytoplasmic eosinophilic globules, focal bizarre nuclear atypia and thin-walled staghorn vessels with widespread hyaline necrosis with no mitotic activity. Immunohistochemical studies demonstrated that the neoplastic cells expressed desmin, SMA, SMMH, and 2SC and were negative for FH; consistent with a FH-deficient leiomyoma.

Results (if a Case Study enter NA)

NA

Conclusion

Although rarely seen, pathologists should be cognizant of FH-deficient neoplasms. Genetic counseling and close follow up of the individuals harboring germline inactivating mutations of the FH gene could lead to early detection of the RCC in these patients and their family members.
Squamous Cell Carcinoma of the Vulva: Clinicopathologic Features of Human Papillomavirus (HPV) Associated and Independent Lesions
Authors: Fernandez M , Kop M , Terada K , Shimizu D , Vierkoetter K R
Published: November 2022

Introduction/Objective

Vulvar squamous cell carcinoma (VSCC) develops via HPV-associated and HPV-independent pathways. Each subset is notable for distinct precursor lesions, morphology, epidemiology and prognoses. There is no consensus regarding the incidence of HPV-associated VSCC, although the literature estimates a range of 15–79%. The current investigation aims to determine the incidence and clinicopathologic features of HPV-associated and HPV- independent VSCC in a diverse, multi-ethnic population.

Methods/Case Report

Resections specimens of VSCC from 1991 to 2020 were retrospectively identified. Cases were reviewed for confirmation of diagnosis, followed by immunohistochemical staining for p16. Age at diagnosis, ethnicity, body mass index, smoking history, tumor size, depth of invasion, and stage were obtained. Statistical analyses included t and Fisher’s exact tests as appropriate, with p<0.05 considered statistically significant.

Results (if a Case Study enter NA)

Sixty-seven VSCC cases were reviewed. By immunohistochemistry, 34 (51%) were HPV-associated. Age at diagnosis was statistically significant (p = 0.0008), with an average age of 63 years for HPV-associated and 75 years for HPV-independent VSCC.Tumor size approached statistical significance (p = 0.0577), with larger tumors occurring in the absence of HPV. Additionally, the incidence of HPV-independent VSCC nearly doubled every 10 years while the incidence of HPV-associated VSCC remained constant.

Conclusion

In this diverse, multi-ethnic cohort, the incidence of HPV-associated VSCC (51%) is at the higher end of the global range of 15-79%. Differences in age demonstrated statistical significance, supporting existing data describing HPV-associated VSCC diagnosed in relatively younger women. Tumor size approached statistical significance, signaling a correlation between HPV-independent VSCC and larger tumors; findings that may support reports of HPV-independent VSCC being associated with a worse prognosis. The increasing incidence of HPV- independent VSCC compared to a constant rate of HPV-associated VSCC suggests changing patterns of detection and pathogenesis.
Automated prognosis marker assessment in 2,004 breast cancers using an artificial intelligence-based framework for BLEACH&STAIN multiplex fluorescence immunohistochemistry
Authors: Mandelkow T , Bady E , Müller J , Debatin N F , Lurati M C , Lennartz M , Sauter G , Blessin N C
Published: November 2022

Introduction/Objective

Introduction: Prognostic markers in routine clinical practice of breast cancer are currently assessed using multi-gene panels. However, the fluctuating tumor purity can reduce the predictive value of such tests. Immunohistochemistry holds the potential for a better risk assessment.

Methods/Case Report

Methods: To enable automated prognosis marker detection (i.e. HER2, GATA3, progesterone-[PR], estrogen- [ER], and androgen receptor [AR], TOP2A, Ki-67, TROP2), we have developed and validated a framework for automated breast cancer identification, which comprises three different artificial intelligence analysis steps and an algorithm for cell-distance analysis of 11 + 1 marker BLEACH&STAIN multiplex fluorescence immunohistochemistry (mfIHC) staining in 2,004 breast cancers.

Results (if a Case Study enter NA)

Results: The optimal distance between Myosin+ basal cells and benign panCK+ cells was identified as 25 µm and used to exclude benign glands from the analysis combined with several deep learning-based algorithms. Our framework discriminated normal glands from malignant glands with an AUC of 0.96. The accuracy of the approach was also validated by well-characterized biological findings, such as the identification of 13% HER2+, 73% PR+/ER+, and 14 triple negative cases. Furthermore, the automated assessment of GATA3, PR, ER, TOP2A-LI, Ki-67-LI and TROP2 was significantly liked to the tumor grade (p<0.001each). Furthermore, a high expression level of HER2, GATA3, PR, and ER was associated with a prolonged overall survival (p≥0.002 each).

Conclusion

Conclusion: A deep learning-based framework for automated breast cancer identification using BLEACH&STAIN multiplex fluorescence IHC facilitates automated prognosis marker quantification in breast cancer.
Malignant Dural Solitary Fibrous Tumor; An Exceedingly Rare Entity
Authors: Kaur N , Hussain F , Al Hmada Y
Published: November 2022

Introduction/Objective

A solitary fibrous tumor (SFT) is an extremely rare mesenchymal neoplasm, accounting for <1% of all primary CNS tumors. Most SFT is dural-based and occurs predominantly in the fourth to sixth decade of life. Here, we present a case of a dural solitary fibrous tumor.

Methods/Case Report

A 28-year-old male presented with intermittent throbbing headache, nausea, and vomiting. Imaging revealed a large, well-circumscribed left parafalcine, dural-based multilobulated, solid, and cystic mass. The patient underwent craniotomy with mass resection. Preliminary intraoperative findings were of a spindle cell neoplasm. Histopathologic examination showed hypercellular neoplasm composed of the spindle to ovoid cells with a high nuclear to cytoplasmic ratio and limited intervening stroma arranged in a haphazard pattern with prominent branching staghorn vasculature. Focal areas of necrosis and mitotic counts of 8/10 high power field were also seen. The lesional cells showed focal cytoplasmic CD34 expression and strong STAT6 nuclear expression. Finally, a diagnosis of SFT, haemangiopericytoma phenotype classified as grade 3, was made.

Results (if a Case Study enter NA)

NA

Conclusion

Most SFTs are considered clinically benign (grade 1 tumors) with favorable outcomes after complete resection. However, haemangiopericytoma phenotype with hypercellularity, necrosis, and elevated mitotic count (> 4/10 HPF) is known to have an increased risk of local recurrence and rare metastasis, requiring patients to receive adjuvant radiotherapy after resection for longer progression-free survival. Therefore, it is vital to be aware of this entity for optimal management and more active systemic surveillance in patients with high-grade SFT tumors. Our patient is currently doing well post-adjuvant radiotherapy and is under active annual surveillance.
Embryonal rhabdomyosarcoma of oropharynx in a 65-year-old male with indolent clinical presentation and unusual morphology
Authors: Surucu A , Hou T
Published: November 2022

Introduction/Objective

Embryonal rhabdomyosarcoma (ERMS) is a malignant primitive mesenchymal tumor which commonly affects children and adolescence. Although head and neck area is a common location for ERMS, oropharynx is rarely involved. ERMS in adults often present with stage IV disease and show a relatively poor prognosis. Loss of heterozygosity in 11p15.5 is one of the common genetic findings in sporadic ERMS.

Methods/Case Report

A 65-year-old male with no significant medical history, presented with pharyngodynia and was found to have a polypoid mass originating from the pharyngeal surface of the soft palate and extends into the vallecula. He reported having this mass for a decade and having intermittent episodes of similar oropharyngeal symptoms which were usually resolved with antibiotics.

Results (if a Case Study enter NA)

Excisional biopsy shows a 2.4 cm polypoid mass with atypical cellular proliferation in submucosa. Tumor cells demonstrate ovoid to round nuclei and eosinophilic cytoplasm. No mitotic figure was found and Ki67 proliferation index was extremely low (<1%). Immunostains showed that the tumor cells are positive for Desmin and MyoD1. Scattered cells are positive for Myogenin. Due to the unusual clinical presentation and low proliferation activity, late onset of fetal rhabdomyoma was also considered in the differential diagnosis. The specimen was sent for chromosomal microarray which showed chromosomal gains and losses including loss of heterozygosity in chromosome 11. This finding together with cytologic atypia are mostly compatible with the diagnosis of ERMS. Post-biopsy MRI and PET-CT did not reveal any residual disease or distant metastasis. Patient has been followed up for 6 months after biopsy with no sign of recurrence.

Conclusion

Our case indicates that ERMS in adult can present with an indolent clinical process and low proliferating activity. Diagnosis can be challenging in this scenario. Chromosomal microarray is a useful tool to help confirm the diagnosis.
A Health Equity Study on Access by Ethnicity to Fecal Immunochemical Testing for Colorectal Cancer Screening at a Veteran Affairs Medical Center
Authors: Petersen J M , Jhala D
Published: November 2022

Introduction/Objective

It has been documented in the literature that significant ethnic and racial disparities in access to healthcare exist. Additionally, it has also been shown that these disparities can be corrected. Integrated health care systems such as the Veterans’ Administration health care system have previously been demonstrated to lead to more equitable care delivery and improved outcomes with lower racial and ethnic differences in access to care. Standard of care guidelines issued by the U.S. Preventive Services Task Force (USPSTF) exist recommending screening for colorectal cancer in adults, of which one of the screening methods involves the convenient fecal immunochemical test (FIT). FIT is a noninvasive simple screening test compared to alternatives such as colonoscopy. Given FIT’s benefits, the authors explored the accessibility by ethnicity for this important test at a Veteran Affairs Medical Center (VAMC).

Methods/Case Report

A search of all FIT testing performed at a regional VAMC from 10/1/2018 to 6/4/2022 was performed to determine the patient demographics including age, gender, and ethnicity. The ethnic distribution of all tested patients was compared to the local census population demographics of the county (Philadelphia) in which the VAMC is located (updated July 1, 2021).

Results (if a Case Study enter NA)

There were a total of 10,110 FIT tests conducted during the study period. From these 10,110 FIT tests, the ethnic composition of the test population is as follows: 5,164 or 51% (5,164/10,110) were African American, 4,389 or 43% (4,389/10,110) were Caucasian American, 65 or 0.6% (65/10,110) were Asian American, 48 or 0.5% were American Indian or Alaska Native American, 111 or 1% (111/10,110) were Native Hawaiian or other Pacific Islander Americans, and 333 or 3.2% (333/10,110) were unknown or declined to state in the medical record. Per the local county census, 44.8% of the local population was Caucasian American and 43.6% were African American.

Conclusion

The VAMC, being an integrated health care system, provides equitable access to FIT to screen for colorectal cancer.
Top Accurate Cell Detection and Segmentation Using A Pen, Agile Digital Image Processing for Deep Learning Models
Authors: Elsafty A M , Ahmed Y M
Published: November 2022

Introduction/Objective

The Hematopathology labs suffer from insufficient productivity, profitability and increased liability. The predicted shortage in the Hematopathologists in the USA is 25% by 2040. Medical errors and results variability due to fatigue and stress could also increase. At least 99% specificity or 99% sensitivity is required in automated visual review of peripheral blood and bone marrow smears to be generalizable and work-fit. Fortunately, the growing digital Hematopathology scanners market besides the vastly developed artificial intelligence (AI) and machine deep learning (DL) technologies could make this realized soon. The AI/DL production cycle includes (1) images collection, (2) image processing/data science, (3) technology, (4) engineering, (5) testing and validation.

Methods/Case Report

Integration with a Hematopathology lab using digital scanners and/or integrated cameras on microscopes is the mean for whole slide images (WSI) collection. Image processing refers to AI/DL spoon-feeding with accurate, diverse and highly-dissimilar materials for learning. This requires providing hundreds of thousands examples of (a) WSI context correction for stain and resolution normalization, (b) cellular dimensions on the WSI patches for detection, (c) cellular segmentation/boundaries determination for counting (d) cellular labels for classification. Comparing with the confirmatory testing results including flow cytometry and immunohistochemistry is essential in both image processing and validation. Currently, image processing resembles 80-90% of the AI/DL cycle/pipeline which may take years of hectic work. Our proposed developed tool enables the Hematopathologists to use pens and draw on the boundaries of each cell in a field/patch. 3-15 seconds are needed for each cell. The required ground truth/masks for segmentation and dimensions for detection are generated in real-time with no need for data scientists.

Results (if a Case Study enter NA)

NA

Conclusion

Similar to the automated agile development-operation loop concept (DevOps), enabling the Hematopathologists to perform image processing directly will reduce the production cycles from years to weeks. No technology can perform qualitatively better than the human eyes, the proposed pen-based cell detection and segmentation tool results in 10-50 fold increase in quality and quantity. Promisingly, there is a trend among the AI/DL platforms companies to automate the AI/DL coding.
Concurrent JAK2 V617F Acute Myeloid Leukemia (AML) and Leukemic non-nodal Mantle Cell Lymphoma (LN-MCL): Case study
Authors: Ohan H , Inamdar K , Shen Y , liu W , Gomez-Gelvez J C , Ghosh S
Published: November 2022

Introduction/Objective

We report a unique case of concurrently occurring Acute Myeloid Leukemia (AML) and Leukemic non-nodal Mantle Cell Lymphoma (LN-MCL) in an 86-year-old male. To the best of our knowledge, this is the first report of AML occurring in the background of LN-MCL, with no known history of any malignancy or chemotherapy.

Methods/Case Report

An 86-year old Caucasian male with unremarkable past medical history presented with pancytopenia, fatigue and generalized weakness. Abdominal CT scan was negative for lymphadenopathy or hepatosplenomegaly. Peripheral blood showed 2% blasts with atypical lymphocytes 89%. Bone marrow aspirate showed 30% myeloblasts expressing CD34, CD117, CD13, CD33, HLA-DR and CD56 (dim) by flow cytometry (FC). Lymphocytes accounted for 40% of bone marrow cellularity. FC identified a population of CD5+ kappa restricted clonal B cells 2%, consistent with a concurrent CD5+ B-lymphoproliferative disorder/lymphoma. The bone marrow biopsy was inadequate for further evaluation of the B- cell lymphoma. Chromosomal analysis revealed a normal male karyotype. FISH analysis was positive for t(11:14) CCND1::IGH rearrangement (in 3.5% of interphase cells) supporting involvement by MCL. Myeloid panel next generation sequencing (51 genes) was positive for JAK2 V617F (VAF, 38%) and ASXL1 P920Tfs*4 (VAF, 22%) variants

Results (if a Case Study enter NA)

NA

Conclusion

Concurrent presence of LN-MCL and AML as seen in our patient in the absence of prior history of malignancy or chemotherapy is rare. Presence of JAK2V617F mutation in de-novo AML is extremely rare (<5%). There is no prior history of myeloproliferative neoplasm (MPN) or CBC data to suggest that this may have progressed from an MPN. While the absence of lymphadenopathy suggests that the CD5+ B-LPD likely represents LN-MCL, it is also likely that the CD5+, IgH/CCND1 rearranged B-cells may represent prior undetected circulating cells without overt LN-MCL development, similar to those reported in otherwise healthy individuals. It is unclear but tempting to speculate that the two co-occurring hematologic malignancies may have a common cell of origin
The Bone Marrow Clinic – The Concept of “Interventional Pathologist”
Authors: ASIF M , Ehsan A , Herschap B , Villa C , Sanchez-Salazar A
Published: November 2022

Introduction/Objective

Bone marrow biopsy (BMBx) is routinely performed and plays an integral role in diagnosing hematologic malignancies. BMBx are performed by mid-level practitioners/hematologists/oncologists (ON), interventional radiologists (IR), and uncommonly by hematopathologists (HP) in hospitals (HO), surgery centers (SC), physician offices (PO). We evaluated: a) cost savings, b) time period of biopsy, and c) impact on diagnosis when HP performed BMBx compared to other providers.

Methods/Case Report

A cross-sectional study was performed. A total of 4640 BMBx at different facilities by various providers were selected. Consent was obtained from patients. 50% (2320) performed by ON; 20% (928) by IR; 30% (1392) by HP. BMBx were performed at following facilities: 30% (1392) - HO; 20% (928) - SC; 50% (2320) - PO.

Results (if a Case Study enter NA)

Patients were divided into two sets based on BMBx performed by providers (Set A - ON, IR, HP) and at facilities (Set B - HO, SC, PO). The average cost for BMBx performed by ON and HP in the PO setting was $175; IR in SC was $1200; and performed at HO irrespective of providers was $3000. In outpatient settings, where the majority of BMBx were performed, the average time to perform BMBx by ON and IR was 10 days vs HP was two days. No difference was noted in HO settings among providers. Lastly, diagnostic samples obtained were superior by HP when compared to ON and IR (degeneration/crushing of cells, hemodilution, and lack of touch imprints).

Conclusion

The pathology curriculum should include evaluation and training for BMBx and other invasive techniques; as this study demonstrates cost savings, improved time to obtain BMBx, and superior quality for analysis when performed by HP. Thus, we emphasized the term “Interventional Pathologists” to describe pathologists directly impacting patient care in the field.
Acute Leukemias of Ambiguous Lineage presenting in Extramedullary Location – Unusual and Challenging Diagnoses: A Report of Two Cases
Authors: Pandiri M , Sallagonda A , Johari V , Freeman J
Published: November 2022

Introduction/Objective

Acute leukemias of ambiguous lineage are uncommon, accounting for <1% of all leukemias, and extramedullary presentations of these leukemias are rare.

Methods/Case Report

We report two cases of acute leukemia of ambiguous lineage presenting in extramedullary sites. Case 1 is a 41-year-old female who presented with right cervical lymphadenopathy and fatigue. Laboratory and imaging studies showed leukopenia, anemia, and abnormal cervical, supraclavicular, axillary, mediastinal, and abdominal pelvic lymphadenopathy. Biopsy of the axillary lymph node revealed sheets of morphologic blasts. Flow cytometry showed the blasts were of mixed phenotype, with T-cell differentiation supported by CD3 and TdT, and myeloid subpopulation supported by myeloperoxidase and lysozyme. Both these populations were negative for CD10, CD20, CD4, CD8, CD34, CD138, CD1a, CD79a. The morphology and immunophenote establish the diagnosis of T/myeloid mixed-phenotype acute leukemia, not otherwise specified. Case 2 is a 65-year-old female who presented with bilateral lower extremity weakness. Multiple lytic lesions involving the thoracic and cervical spine were detected by imaging. Biopsy of a T12 vertebral lesion revealed sheets of large malignant cells. Extensive immunohistochemical workup revealed positivity for CD45 (weak), CD4, and CD43, supporting a diagnosis of hematopoietic neoplasm of likely hematopoietic origin. Subsequent evaluation eventually led to discovery of chronic myeloid leukemia in blast phase with undifferentiated blasts, BCR-ABL1 positive, originally presenting as extramedullary acute leukemia with undifferentiated blasts.

Results (if a Case Study enter NA)

NA.

Conclusion

These cases highlight the challenges of diagnosing peripheral solid tumors of unknown origin. Extramedullary presentation of acute leukemia of ambiguous lineage are particularly challenging and, although rare, include phenotypes ranging from mixed phenotype to undifferentiated types.
A Unusual Case of Classic Hodgkin Lymphoma (cHL) with Aberrant T-Antigens Expression
Authors: Gaddam S , Oyedeji O , liu W , Gomez-Gelvez J C , Inamdar K , Carey J , Shen Y
Published: November 2022

Introduction/Objective

T-cell-associated antigens (TCA) are rarely expressed by Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) and is associated with uncertain clinical significance.

Methods/Case Report

We present a very recent case of a 68 year-old female with no significant past medical history presented with a large right groin mass for 1 month. She denied any fever, night sweats, fatigue or weight loss. CT abdomen/pelvis showed inguinal/pelvic lymphadenopathy. Resection showed effaced nodal architecture with a vague nodular appearance and with large, atypical nucleolated cells in a background of small, mature lymphocytes and histiocytes. Eosinophils are conspicuously absent in the background. The large cells were polylobated lymphocyte and histiocyte rich (L & H) like, classic HRS cells as well as multinucleated in appearance. The morphologic features overlapped between Classic Hodgkin Lymphoma, and Nodular Lymphocyte Predominant Hodgkin Lymphoma. Given the immunohistochemical (IHC) features of the neoplastic cells [CD45 negative, PAX5+ (weak), CD30+ (strong), CD15+ (majority) and MUM1 +] the diagnosis was most compatible with CHL. Interestingly, a subset of the Hodgkin cells (10-20%) aberrantly expressed a number of T-cell markers (CD2, CD3, CD4, and CD8). However, the background smaller T-cells did not show cytologic atypia or aberrancies of T-cell antigen markers. The large cells were negative for CD43 and ALK1. TCR gamma gene rearrangement was also negative for clonal T-lymphocytes, thus excluding the possibility of peripheral T-cell lymphoma with Hodgkin-like cells. Based on the morphology and IHC profile, this case proves to be CHL with multiple TCA expression including CD2, CD3, CD4 and CD8. She was planned for chemotherapy. Four months after the initial diagnosis and after completion of 2 cycles of chemotherapy, her PET CT scan showed improvement with right inguinal adenopathy being smaller in size and decreased avidity, indicating a response to treatment. She is due for 2 more cycles. Till todate she is doing well with no further symptoms.

Results (if a Case Study enter NA)

NA.

Conclusion

So far reported cases of classic Hodgkin lymphoma (CHL) with aberrant T-cell antigen (TCA) expression were associated with decreased event-free survival and overall survival when compared with TCA-negative CHLs. Our finding contributes to the literature and improves our knowledge of the disease.
An Unusual Extramedullary Presentation of an NPM1-Mutated Acute Myeloid Leukemia (AML) in a Young Adult
Authors: Percy M C , Redemann J , Babu D , Marshall T
Published: November 2022

Introduction/Objective

Pleural effusion presentation of AML, particularly without leukemic disease, has been rarely described in the literature. This case serves to investigate the value of an identified NPM1 mutation.

Methods/Case Report

A 25-year-old male with Down syndrome presented with dyspnea. Computerized tomography scan identified a moderate pleural effusion and pelvic lytic bone lesions. A complete blood count was normal. Pleural fluid cytologic evaluation showed a spectrum of immature myeloid precursors, and flow cytometry identified a 23% CD117 positive myeloblast population expressing CD33, CD13, and dim CD45 but lacking CD34 and HLA-DR. Fluorescence in-situ hybridization testing was negative for a PML-RARA fusion. Given the phenotype, molecular testing was initiated and confirmed an NPM1 mutation. Testing revealed additional pathogenic variants in DNMT3A and IDH1 with no FLT3 mutations. Peripheral blood smear and bone marrow evaluations yielded no clear leukemic involvement, and cytogenetics from bone marrow showed 47,XY,+21c[20]. The significance of this myeloid infiltrate was initially not entirely clear with no established leukemic involvement or tumor-forming mass as required for the World Health Organization diagnosis of myeloid sarcoma. However, the finding of the NPM1 mutation lent high confidence for a diagnosis of an extramedullary presentation of acute myeloid leukemia, though the lytic bone lesions were not biopsied to possibly demonstrate a myeloid sarcoma.

Results (if a Case Study enter NA)

N/A.

Conclusion

The identified NPM1 mutation was instrumental in diagnosing an unusual presentation of AML where material was limited. Subsequent to this presentation the patient developed more overt leukemic disease at an outside institution, additionally supporting this diagnosis.
Whole Exome-Sequencing Identifies Variants Associated with Harris Platelet Syndrome
Authors: Das A , Naina H V , Venigalla S S
Published: November 2022

Introduction/Objective

Introduction: Harris platelet syndrome (HPS) is an autosomal dominant giant platelet disorder characterized by normal platelet function with varying degrees of thrombocytopenia. HPS was initially reported in healthy blood donors from West Bengal, and subsequent studies showed it is prevalent in healthy blood donors from the northeastern part of the Indian subcontinent. Objective: Whole-exome sequencing was performed to identify single-nucleotide polymorphisms in protein-coding genes and the associated pathways between the cases and controls.

Methods/Case Report

Methods: HPS is defined as healthy blood donors having a mean platelet volume (MPV) greater than 12 fL (normal <10 fL) with or without concomitant thrombocytopenia in the absence of any significant past history of bleeding disorder in either themselves or their first-degree relatives. HPS and control healthy donors were enrolled in the study with proper consent. Plasma is extracted from 15 ml of blood samples that were drawn from subjects, and whole-exome sequencing was done on the samples. Pathway analysis of candidate genes and interaction mapping was done using Reactome Pathway Database and STRING, respectively.

Results (if a Case Study enter NA)

Results: Whole-exome sequencing from the plasma from HPS and non-HPS subjects (n=5 in each group) identified 1374 differentially expressed genes between the two groups. There was a total of 42 single nucleotide polymorphisms (SNPs), (5 deletions and 1 insertion) in the cases (either heterozygous or homozygous) but not in controls. 13 pathways were associated with these variants, and iron homeostasis and defective Cubulin (CUBN) were the top among the predicted pathways. HDL clearing, vitamin and cofactor transport, metabolism, and cardiac conduction defects were among the significantly predicted pathways affected by the variants in HPS patients. An interaction map of the 25 differentially expressed genes where the variants can be mapped is prepared.

Conclusion

Conclusion: This study shows that SNP variants in HPS may be associated with pathways related to iron homeostasis, HDL clearing, vitamin metabolism and transport and cardiac conduction defects. Phenomapping of HPS patients with detailed genotyping in large population cohort studies are necessary to validate and characterize the functional effect of HPS variants.
Clinical Application of Rapid PCR and Computational Digital Pathology for Cancer Diagnostics: A showcase for Advanced Lung Cancer Management
Authors: Hoo-Fatt N , Ullah A , Nam M
Published: November 2022

Introduction/Objective

While there has been a significant increase in our understanding of the molecular changes that occur during cancer growth, the clinical efficacy of molecular testing for cancer diagnosis treatment for advanced cancers has been limited .The objective of this project is to determine the use of rapid molecular tests with same-day turn-around-time (TAT) for tumor mutations and the application of objective AI-based digital scoring methods of Immunohistochemistry test for PD-L1 for Keytruda® (Pembrolizumab). These targeted therapies for various cancers will improve patient care by reducing turnaround time and increasing diagnostic accuracy of cancer biomarker testing.

Methods/Case Report

A combination of rapid EGFR assays, IHC for PDL1 and digital pathology scoring was used. The data received was then used for genome-wide correlation analysis of human gene CD274 and the RNA-seq dataset from The Cancer Genome Atlas (TCGA).

Results (if a Case Study enter NA)

Our preliminary study results showed that there is a correlation between Micro-RNA expression of PD-L1 and immunohistochemistry PD-L1 stains. Some micro-RNA expression showed over- expression of PD-L1, which resulted in high PD-L1 IHC score. This shows that there may be a case for more bio marker studies to aid in predicting of the response to PD-L1 pathway inhibitors. The rapid molecular testing results were also comparable to next gen sequencing (NGS) in determining the EGFR mutations. Future studies include the training of the PD-L1 AI algorithm for scoring to be used as a diagnostic companion and the use of immune based metrics to study the response and resistance to immunotherapy in non-small cell lung cancer(NSCLC).

Conclusion

We would like to showcase a combined modality diagnostic biomarker testing system that can allow the clinical decision on the targeted therapy in 24-48 hours. With the approval of Keytruda® (Pembrolizumab) in many advanced cancers, we believe that our approach for NSCLC will provide fast and high quality results for timely treatment of patients.