bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropathologic Findings and Electrolyte Abnormalities in a Case of Lennox-Gastaut Syndrome (SCN2a- related) Encountered at Autopsy
Authors: Thompson C T , Khatskevich K , Welsh C , Baker T , Butler D C
Published: October 2024

Introduction/Objective

Lennox-Gastaut syndrome is a severe form of childhood epilepsy which may be due to several conditions, including sodium channelopathies which alter neuronal firing patterns. We present a case of a 6-year-old female with Lennox-Gastaut syndrome (SCN2A-related) complicated by developmental delay, spastic quadriplegia, and gastrojejunostomy tube dependence who was referred for medicolegal autopsy due to death subsequent to becoming unresponsive during a supervised bath.

Methods/Case Report

A complete autopsy was performed, including gross and microscopic examination of all primary organ systems, formal neuropathologic examination, and postmortem microbiology, toxicology, and vitreous electrolyte studies.

The decedent showed evidence of developmental delay and flexion contractures of the extremities. No significant traumatic injuries were identified. A postmortem nasopharyngeal swab was positive for Rhinovirus/Enterovirus and Influenza A H3. A postmortem vitreous electrolyte panel demonstrated a dehydration pattern, including markedly elevated sodium and chloride and elevated urea nitrogen. Gross examination of the brain showed a thin corpus callosum, small hippocampi, as well as abnormal cerebellar dentate and inferior olivary nuclei. Microscopic examination of the brain tissue supported the gross findings, including dentato-olivary dysplasia.

The cause of death was certified as dehydration complicating Lennox-Gastaut syndrome (SCN2a-related). Rhinovirus/Enterovirus and Influenza A H3 infections were considered contributory to death. The manner of death remained undetermined, since it was unknown if the decedent’s natural diseases, issues following a scheduled gastrojejunostomy feeding regimen, neglect, or some combination thereof caused the dehydration.

Results (if a Case Study enter NA)

NA

Conclusion

This case highlights unique and rarely documented neuropathologic findings and electrolyte abnormalities that may be seen in Lennox-Gastaut syndrome associated with an SCN2A mutation in addition to demonstrating the challenges of cause and manner death certification in cases of severe developmental disorders of childhood related to sodium channelopathies.
Death Due to Embolic Renal Cell Carcinoma
Authors: Jolly A L , Love G
Published: October 2024

Introduction/Objective

While most pulmonary embolisms are composed of blood clot resulting from venous stasis, tumor embolism is rarely encountered. We describe an autopsy patient with an unexpected renal cell carcinoma (RCC) who expired after a massive tumor embolism to the pulmonary artery.

Methods/Case Report

A 56-year-old male presented with complaints of shortness of breath and was found to have a large right-sided pulmonary embolism with an incidental finding of a 9.0 cm right kidney mass on imaging. He was subsequently admitted for further management consisting of thrombo-aspiration. The procedure was largely unsuccessful and the patient’s respiratory status continued to decline and he subsequently expired. On autopsy, a 9.3 x 6.2 x 6.0 cm, yellow-tan, well-defined mass was discovered primarily in the lower pole of the right kidney with invasion into the hilar structures. The mass grossly appeared to be invading into the renal vein. Two large yellow-tan emboli were found to be causing significant obstruction of the inferior vena cava at the level of the right renal vein and in the right pulmonary artery. Microscopic evaluation revealed the kidney tumor to be consistent with renal cell carcinoma morphologically and immunohistochemically. Interestingly, all emboli discovered at autopsy are primarily composed of sheets of cells identical to the patient’s renal mass. It is therefore concluded that the patient’s kidney cancer invaded into the renal vein and embolized to the pulmonary artery, ultimately resulting in death.

Results (if a Case Study enter NA)

NA

Conclusion

Tumor embolism is a rare cause of death. Renal cell carcinoma is a relatively common neoplasm that has been described to present as a tumor thrombus in 13.3% of patients. Of these patients with RCC tumor thrombus, 1% embolize to the right atrium. Our case represents this rare phenomenon and demonstrates why it is crucial to confirm the contents of a pulmonary embolism, as not all are composed of blood components alone.
Giant pilomatricoma with atypical features: report of a case of aggressive pilomatricoma in an adult
Authors: Johal J J , Mateescu V , Dai H , Augustin S M
Published: October 2024

Introduction/Objective

Pilomatricoma, also known as pilomatrixoma or calcifying epithelioma of Malherbe, is a relatively common, benign tumor of the hair matrix. It typically presents as a small (~1cm), dermal based mass in the head and neck region of children and young adults (under 20 years) with predominance for males, but can occur in any age. In contrast, malignant pilomatricoma is typically larger (1 to 10 cm) and occurs later in life (50-60 years).

Aggressive pilomatricoma is a variant of pilomatricoma that tends to occur in children and demonstrates atypical features such as increased matrical cells and nuclear atypia, but insufficient for a classification as pilomatrical carcinoma. Here, we presented a case of a large (14.5 cm) aggressive/atypical pilomatricoma that occurred in an adult.

Methods/Case Report

A 45 year-old-female presented to the emergency department with a posterior neck mass which has been slowly enlarging for years. Recently, it became painful with sanguineous discharge which prompted her to seek medical attention. CT scan revealed a lobulated, pedunculated mass with fat and fluid components. An excision was performed. Gross examination revealed an ulcerated mass measured 14.5 cm in greatest dimension. Scattered calcifications were present. Microscopically, nests of basaloid cells with scattered shadow cells are present consistent with matrical differentiation. A multinodular growth pattern with central necrosis was evident. Nuclear atypia characterized by prominent nucleoli and nuclear overlapping was identified.

Results (if a Case Study enter NA)

NA

Conclusion

Histopathologic criteria to reliably differentiate between benign and malignant pilomatrical tumors are not well-established. Tumor ulceration, asymmetry, irregular borders, multinodular growth pattern, marked cytologic atypia, prominent necrosis, lymphovascular invasion, and perineural invasion may be used in favor of malignancy. Our case showed focal confluent necrosis, ulceration, multinodular growth pattern, and cellular atypia but lacked other features that indicative of unequivocal malignancy. The resection margins were negative for tumor. Clinical followup was negative for signs of recurrence or metastasis after two years. We presented this case to show the large size that aggressive pilomatricoma can reach and to emphasize the difficulty in differentiating benign from malignant pilomatrical tumors in borderline cases.
Intravascular Nodular Fasciitis Mimicking Thrombotic Complications in a 16-year-old male with May-Thurner Syndrome
Authors: Ak S , Abu Qubo A , Ibrahim N , TAKEI H , Thomas-Ogunniyi J O
Published: October 2024

Introduction/Objective

Nodular fasciitis is a rare benign myofibroblastic proliferation commonly mistaken for malignant tumors due to its rapid growth and clinical presentation. May-Thurner Syndrome (MTS), characterized by compression of the left common iliac vein by the right common iliac artery, predisposes individuals to deep vein thrombosis (DVT). However, here we present a unique case of intravascular nodular fasciitis presenting as thrombotic complications in the context of MTS in a 16-year-old male.

Methods/Case Report

A 16-year-old male presented with progressive left hip and leg pain accompanied by recent swelling. Ultrasound revealed occlusive thrombi within the left side external iliac, common superficial femoral, and great saphenous veins, along with nonocclusive thrombi in left deep femoral vein. Magnetic resonance venography confirmed MTS and extensive thrombosis. Thrombectomy was done with fragments sent to pathology. Microscopic examination showed cellular areas with loose myxoid composition, proliferating spindle, myofibroblastic/fibroblastic, and stellate cells arranged in irregular bundles. Additional microscopic findings included mild cellular atypia, mitoses, focal macrophage aggregates, occasional multinucleate forms, foci of hemorrhage, fibrin exudate, ingrowing fibroblasts, and increased vascularization. Immunohistochemical stains demonstrated positivity for SMA, CD31, ERG, and CD34, highlighting prominent vascularization, while desmin, myogenin, myoglobin, STAT6, beta-catenin, S100, and AE1/AE3 were negative. Differential diagnosis included intravascular fasciitis, and possibly organizing thrombus with myxoid stroma. USP6 gene rearrangement (FISH) study was positive, confirming the diagnosis of nodular fasciitis.

Results (if a Case Study enter NA)

N/A

Conclusion

This case emphasizes the significance of maintaining a broad differential diagnosis when assessing specimens sent as thrombectomies. Recognizing intravascular nodular fasciitis as a potential presentation mimicking thrombosis is essential for accurate diagnosis and management.
Superficial angiomyxoma-like myxofibrosarcoma
Authors: Abdo M E , AL-Kharouf I , Elsafy H , Hamza A , Meyer A R
Published: October 2024

Introduction/Objective

Myxofibrosarcoma comprises a spectrum of malignant fibroblastic neoplasms with variably myxoid stroma, pleomorphism, and a distinctive curvilinear vascular pattern. Herein we describe a case of myxofibrosarcoma with unusual histological features that could be deceptive, mimic superficial angiomyxoma and make the diagnosis challenging

Methods/Case Report

A 74-year-old female presented with a right upper arm lesion that had been present for 10-12 months and had significantly increased in size over this time and became painful. There was no history of trauma.

Examination demonstrated approximately 3 cm multinodular mass along the anterior aspect of the proximal arm. There were no overlying skin discolorations or ecchymosis. The patient underwent a shave biopsy and then resection. Grossly, the lesion was gray-white firm with an ill-defined border covered with a tan-white skin ellipse. Histologically, the lesion was located in the dermis extending to the dermal-epidermal junction. The lesion comprised mainly of myxoid stroma, arborizing, and plexiform thin-walled blood vessels, stellate to spindled cells with enlarged hyperchromatic nuclei, and eosinophilic cytoplasm in addition to the presence of stromal neutrophils and hyperplastic overlying squamous epithelium. The morphologic appearance elicited the differential diagnosis of superficial angiomyxoma and low-grade myxofibrosarcoma. While many features were more suggestive of superficial angiomyxoma, the degree of atypia and mitotic activity (12/10 HPF) was outside the realm of angiomyxoma and warranted the diagnosis of myxofibrosarcoma

Results (if a Case Study enter NA)

NA

Conclusion

Although rare, myxofibrosarcoma may rarely extend to the dermal-epidermal junction and mimic superficial angiomyxoma. The presence of cytologic atypia and increased mitotic activity favors myxofibrosarcoma
Rare Presentation of Extraskeletal Osteosarcoma Mimicking Phyllodes Tumor
Authors: Ndam F , Alrammahi A , Snower D
Published: October 2024

Introduction/Objective

A 57-year-old female presented with a palpable mass in the left breast, measuring up to 9 cm by ultrasound. core needle biopsy identified an atypical spindle cell lesion. The differential diagnosis included a metaplastic carcinoma, borderline phyllodes tumor, malignant phyllodes tumor with potential sarcomatous transformation.

Methods/Case Report

Histological examination of the tumor was performed, and immunohistochemical stains were conducted to characterize the lesion. Further consultation with a specialized pathologist at the University of Michigan was sought to confirm the diagnosis. Molecular analysis was performed to assess for specific genetic alterations and expression patterns.

The histological examination revealed a proliferation of atypical spindle cells forming a fascicular and storiform pattern, with numerous large, pleomorphic, multinucleated tumor cells and a high mitotic rate. Immunohistochemical stains showed strong positivity for CD10 and vimentin, with focal weak expression for desmin, and negativity for a broad panel of cytokeratins and other markers. Consultation with Dr. Abbott at the University of Michigan supported the diagnosis of extraskeletal osteosarcoma. Molecular analysis revealed PD-L1 expression and absence of NTRK gene fusions. FISH analysis showed suggestive alterations including loss of BRAF gene, loss of MYC, and suggestive gains or polysomy of PTEN gene.

Results (if a Case Study enter NA)

NA

Conclusion

The case represents a rare presentation of extraskeletal osteosarcoma in the breast, with distinctive histological and immunohistochemical features. The comprehensive workup including histology, immunohistochemistry, and molecular analysis aids in accurate diagnosis and potential therapeutic implications. Further research may elucidate the underlying mechanisms and treatment options for this uncommon malignancy.
A Case for Co-oximetry: Methemoglobinemia secondary to a Rare Hemoglobin Variant
Authors: Olaniyan H S , Zimmerman M
Published: October 2024

Introduction/Objective

The presence of dyshemoglobins and some inherited hemoglobin (Hb) variants can cause over or underestimation of oxygen saturation (O2sat) when using a pulse oximeter (ox). These noninvasive medical devices rely on two wavelengths, a pulsing arterial bed, and light absorption properties of Hb to measure the difference between deoxy- and oxy-Hb. In contrast, a co-oximeter (co-ox) requires arterial blood. By using at least four wavelengths, co-ox measures the functional and fractional O2sat to detect all forms of Hb, including those that do not bind oxygen (O2), such as methemoglobin (metHb). Methemoglobinemia may be congenital or acquired, resulting from exposure to certain toxins, metabolic disorders, enzymatic deficiencies such as cytochrome b5 reductase deficiency, or hemoglobinopathies.

Methods/Case Report

A healthy, adolescent male undergoing a sports physical at his pediatrician’s office was hypoxic by pulse ox and sent to the emergency department (ED) for evaluation. On exam, he had cold, blue tinged fingertips and lips but was otherwise asymptomatic. His O2sat was 88-90% on room air with minimal improvement with 6L of supplemental O2. Co-ox revealed a metHb level > 20%. The father also mentioned that the mother had frequent ED visits for hypoxia.

Capillary Hb electrophoresis showed peaks in the HbA, HbF, and HbA2 zones of 78.3%, 17.9%, and 3.6%, respectively. All CBC parameters were within the reference intervals. The large peak in the HbF zone would suggest hereditary persistence of fetal hemoglobin (HPFH); however, the clinical picture was not consistent. Further reference laboratory investigation determined that the patient was heterozygous for Hb Tübingen (HbTüb), a beta globin chain variant resulting from a point mutation at position 106. By mass spectrometry, the variant quantified as 38% of the total hemoglobin, indicating underestimation by electrophoretic techniques.

Results (if a Case Study enter NA)

NA

Conclusion

This case presents an essentially asymptomatic patient with hypoxia and elevated methemoglobin levels. Electrophoretic hemoglobinopathy and CBC workup were clinically inconsistent with HPFH and the presence of an aberrant hemoglobin migrating in the HbF must be considered in the differential diagnosis. The manifestation of HbTüb as methemoglobinemia in this context adds complexity to the diagnostic puzzle. Further laboratory exploration into the underlying mechanisms driving this unique presentation is crucial for a comprehensive understanding and tailored management approach.
Preparation and Characterization of Berberine-Loaded Bovine Serum Albumin Nanoparticles: Encapsulation Efficiency and Release Rate Determination
Authors: Abdelmonem M , Hemdan A , Ghareeb D , El demellawy M , El sayed M , Abdelmageed M , Wasim H
Published: October 2024

Introduction/Objective

Introduction: Berberine (BER) has garnered attention in various studies for its diverse biochemical and pharmacological properties, including anti-inflammatory, antioxidant, antidepressant, anticancer, antihyperglycemic, hypolipidemic, antihypertensive, and hepatoprotective effects. Nanoparticles serve as efficient carriers for drugs, offering increased surface area and enhanced dissolution in the bloodstream, thereby improving drug delivery.

Methods/Case Report

Methods: Blank Bovine Serum Albumin Nanoparticles (BSA NPs) were synthesized using a desolvation process, followed by the fabrication of Berberine-loaded Bovine Serum Albumin Nanoparticles (BER-NP). Physicochemical characterization, including particle size and zeta potential, was conducted using a Malvern Zetasizer and dynamic light scattering (DLS). Transmission electron microscopy (TEM) was employed to visualize the morphology of both blank BSA NPs and BER-loaded nanocarriers.

Results (if a Case Study enter NA)

Results: Fourier-transform infrared (FTIR) spectra and Differential Scanning Calorimetry (DSC) thermograms were obtained for free berberine, BSA NPs, and BER-NPs. Encapsulation efficiency (EE) was determined by measuring the concentration of free BER in the supernatant after centrifugation, with EE calculated based on the difference between total added berberine and the measured supernatant concentration.

Dialysis membranes were utilized to assess BER release from BER-NPs in vitro, with initial BER content in nanoparticles determining the release profile.

Conclusion

Conclusion: The prepared nanoparticles have demonstrated the potential to enhance drug permeation across epithelial and endothelial barriers. This approach holds promise for targeted drug delivery to specific sites, facilitating combined therapy with distinct modalities or drugs.
Metastatic Carcinosarcoma with a Sarcomatous Predominance?
Authors: Abraham H , Bassham C , Chinchanikar S , Omoscharka E
Published: October 2024

Introduction/Objective

Uterine carcinosarcoma (CS), also known as Malignant Mixed Müllerian Tumor, is a malignancy characterized by mixed epithelial and mesenchymal components. It is rare and aggressive, most frequently occurring in elderly, postmenopausal women with a median age of 65 years. CS has a tendency to metastasize with an overall poor prognosis. Fine needle aspiration can be useful in identifying metastatic disease, however, demonstration of both sarcomatous and carcinomatous components can be difficult.

Methods/Case Report

Our patient is a 68 year old female who was first diagnosed with endometrial carcinosarcoma on an endometrial biopsy in 2022. She subsequently underwent a total abdominal hysterectomy with radical dissection, bilateral salpingo-oophorectomy, upper vaginectomy, sentinel lymph node dissection as well as chemotherapy. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 all showed intact nuclear expression.

Remission was achieved for about a year, after which she was found to have a moderate right sided pleural effusion with right lower lung infiltrates. Also, a right upper lobe mass was reported on chest CT scan. Paracentesis was performed and cytology was consistent with predominantly atypical spindle cells accompanied by a mixed inflammatory infiltrate. Immunohistochemical stains were performed on the cell block, tumor cells were positive for smooth muscle actin, vimentin and negative for desmin, S-100, SOX-10, CD34, P63, TTF-1 and pancytokeratin.

Cytology diagnosis was rendered as malignant cells present, consistent with metastatic CS. A subsequent lung mass core biopsy also confirmed the diagnosis.

Results (if a Case Study enter NA)

NA

Conclusion

The cytomorphological features in effusion samples from metastatic CS have the carcinomatous component readily identifiable, and only a minority of effusion samples show additional sarcomatous component. The exact diagnosis of CS may not be possible due to the absence of sarcomatous components. Alternatively, as we present in this rare case of metastatic CS, the sarcomatous component in the form of abundant atypical oval to spindle cells with hyperchromatic nuclei may be the only form of malignant cells present in the specimen. Careful morphological assessment of architectural patterns, a good past medical history, availability of cell blocks and immunohistochemistry are vital in providing an accurate diagnosis in such rare cases of metastatic CS.
RETROSPECTIVE ANALYSIS OF DISCORDANT RESULTS BETWEEN UROVYSION FISH AND URINE CYTOLOGY IN THE DETECTION OF HIGH-GRADE UROTHELIAL CARCINOMA (HGUC): A STUDY OF 118 PATIENTS
Authors: Ur Rehman A , Liu J , Elsayad M
Published: October 2024

Introduction/Objective

Accurate detection of high-grade urothelial carcinoma (HGUC) relies on multiple diagnostic modalities, including UroVysion FISH and urine cytology; however, discordant results between these diagnostic tools can present a challenge. We present this study, scrutinizing the discordant results between UroVysion FISH and urine cytology to explore the potential factors that could contribute to discrepancies.

Methods/Case Report

A cohort of 118 patients, who underwent both UroVysion FISH and urine cytology testing for evaluation of HGUC, was selected from our cytopathology archives. Results of both the modalities were compared, and a retrospective review of original slides was done by experienced cytopathologists.

Results (if a Case Study enter NA)

Among the 118 cases, Urovysion FISH yielded positive results in 14 cases and negative in 104. In contrast, urine cytology reported 1 case as positive, 102 as negative, 10 as atypical (8 atypical and 2 rare atypical), and 5 as suspicious. Discordant findings were observed in 20 cases, accounting for 17% of the cases. After retrospective review of original slides, few cases were reclassified. 2 cases as atypical (initially labeled as negative), 2 cases as negative (initially labeled as atypical), 3 cases as positive (initially labeled as atypical/suspicious), 3 cases as suspicious (initially labeled as negative/atypical).

Conclusion

This reclassification highlights complexity of cytological interpretation, including the challenges of distinguishing between benign cellular alterations, reactive changes, ambiguous findings, suspicious features and malignant cytological changes. Integrating molecular and morphological assessment is essential for evaluation of urothelial carcinoma. Discrepancy between the two is an area which is open to study and can be related to differences in sensitivity and specificity of the testing modalities, sampling methods, variation in interpretation, limitations of testing modality and varying tumor characteristics. Review of clinical history, imaging studies, cystoscopy, and repeat testing may be considered in such cases for diagnostic accuracy.
An Unusual Skin Finding in a Rare Case of Goltz Syndrome
Authors: Irfan A , Gener M
Published: October 2024

Introduction/Objective

Goltz Syndrome (Focal Dermal Hypoplasia) is a rare X linked dominant genetic disorder with various dermatologic, musculoskeletal and neurologic manifestations, secondary to a mutation in the PORCN gene. Skin findings include telangiectasias, raspberry-like papillomas (angiofibroma like lesions), nodular fat herniation, xerosis and photosensitivity. Lesions are bilateral, and asymmetrically distribututed along the lines of Blasco. The adipocytic lesions can be diagnosed via a skin biopsy showing adipose tissue in the superficial epidermis and dermis or via molecular techniques showing a mutation in the PORCN gene. Here we report a case of Goltz Syndrome with unique dermal findings.

Methods/Case Report

A male infant presented at birth with mild diffuse xerosis, large hypopigmented and depigmented atrophic patches and plaques and multiple pink yellow red exophyitic soft papules distributed asymetrically across the body along the lines of Blascho. Additionally the patient had clinodactly, widely spaced nipples, extra pads of fat in the toes and philtrum and fingernails with longitudal ridges and lateral nail plate deviation. A diagnosis of Goltz syndrome was made via molecular analysis that showed mosiacism at C.502G>A (p.Gly168Arg) in the PORCN gene.

The patient had a very superficial 2-3 mm erosion at the intersection between the scrotum and perineum. At 18 months, this had grown to finger like projections and eventually grew into multiple tan red exophytic warty papillomatous telangactatic like lesions measuring 3.0 x 0.8 cm that were painful and bled easily. A biopsy of this lesion showed focal mild epidermal hyperplasia and elongation of the rete ridges with wide spread diffuse vascular proliferation with multiple ectactic vessels along with mild dermal and perivascular inflammatory infiltrates. Also noted was infiltration of mature adipose tissue in the superficial epidermis and dermis. We preformed elastin and trichrome stains to identify if this lesion was reactive in nature or de novo. Our results showed retained elastin staining with a negative trichrome eluding to a denovo process. Additionally GLUT1 was negative, ruling out an infantile hemangioma. The above findings in this lesion do not represent any previously described dermatologic entity.

Results (if a Case Study enter NA)

NA

Conclusion

This is a rare and unique dermatologic finding of a case of Goltz sydrome, which itself is a rare disorder. In our literature review, this is the only case of Goltz Syndrome thusfar to have presented with this unique skin lesion.
Squamoid eccrine ductal carcinoma of the vulva: A case report
Authors: Gandhi S , Fraga G , Lankachandra K
Published: October 2024

Introduction/Objective

A 53-year-old female sought medical attention for left vulvar pain and a vulvar lesion.

Methods/Case Report

Physical examination revealed a 1.0 x 1.0 cm lesion within a background of lichen sclerosus. Biopsy demonstrated a carcinoma with tubular and glandular architecture, areas of squamoid differentiation and widespread perineural invasion. Ancillary immunohistochemistry testing with keratin 7 highlighted foci of ductal differentiation. Tumor cells were also positive for p53, p63, pankeratin, and keratin 5/6. The Ki-67 proliferation index was approximately 15%. Tumor cells were negative for Keratin 20, PAX 8, p16, and CD 34. We diagnosed the lesion as a vulvar sweat gland adenocarcinoma of the squamoid eccrine ductal subtype.

Results (if a Case Study enter NA)

N/A

Conclusion

Carcinomas of vulvar sweat gland origin are extremely rare, comprising less than 1% of all vulvar cancers. To the best of our knowledge, this is the first case report of squamoid eccrine ductal carcinoma afflicting the vulva.
Ethnic Access to and Usage of Microsatellite Instability/Mismatch Repair Testing on Colon Cancers at a Regional Veteran Affairs Medical Center
Authors: Petersen J M , Jhala D
Published: October 2024

Introduction/Objective

It has been a National Comprehensive Cancer Network (NCCN) recommendation since 2015 that all colon carcinoma cases should receive mismatch repair and microsatellite instability (MSI/MMR) testing.

However, literature on MSI/MMR testing compliance with this recommendation particularly for ethnic minorities and veterans, are sparse in the literature.

Methods/Case Report

A retrospective review of all invasive colon carcinoma cases from colon or rectum specimens was performed from 2017 to March 8th, 2024, at a regional Veteran Affairs Medical Center (VAMC) as part quality assurance (QA) to collect test performance and demographic information. There had been clinical team/pathologist regular education about the NCCN guidelines.

Results (if a Case Study enter NA)

There were 210 cases from which 183 out of 219 cases (84%) included MSI/MMR testing. From the total population of 210, 92 (43.8%) were African American, 107 were Caucasian American (51.0%) and others were 11 (5.2%). Among the 183 with MSI/MMR testing, 79 (43.2%) were African American, 94 were Caucasian American (51.4%), with the remainder being 10 (5.5%).

Testing rate for MSI/MMR over the years increased from 2021 onwards: 40 out of 43 cases in 2017 (93%), 22 out of 27 in 2018 (81%), 27 out of 33 in 2019 (81%), 24 out of 27 in 2020 (88%), 25 out of 34 in 2021 (74%), 21 out of 21 out of in 2022 (100%), and 24 out of 25 in 2023 to 2024 (96% with 1 patient expiring before testing could be sent).

Conclusion

From 2022 onwards, all patients received MSI/MMR testing if not expired, which is a substantial improvement demonstrating the impact of education and awareness of the current NCCN guidelines along with its impact on patient management. Furthermore, the VAMC provided equal access to MSI/MMR testing to all ethnic groups, thus serving as a paradigm for health equity for colon cancer testing.
Malignant Peripheral Nerve Sheath Tumor of the Pancreas with Molecular Confirmation: A Case Report with Comprehensive Histopathologic and Molecular Characterization
Authors: Chitsaz M , Kaufman T , Macaulay R , Henderson-Jackson E , Nakanishi Y
Published: October 2024

Introduction/Objective

Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue sarcomas arising from a peripheral nerve or exhibiting nerve sheath differentiation. They are often associated with neurofibromatosis type 1, and most often arise in the trunk, extremities, or head and neck region. In patients without neurofibromatosis type 1, sporadic de novo or radiotherapy-associated MPNSTs can pose a diagnostic challenge. MPNSTs arising from visceral organs are exceedingly rare. Here we report a case of MPNST arising in the pancreas.

Methods/Case Report

The patient is a 75-year-old female, MUTYH mutation carrier, with prior history of breast and bladder cancers, each treated with respective local excision and radiation therapy. Magnetic resonance imaging (MRI) performed for pancreatic cancer screening showed a 4.7 cm heterogeneous mass in the pancreatic tail suggestive of pancreatic neoplasm. Fine needle aspiration cytology was non-diagnostic. However, due to the radiologic concern for malignancy, the patient proceeded with surgical resection by distal pancreatectomy with splenectomy.

Macroscopically, a 6.5 cm, tan-white, partially necrotic mass was identified in the pancreatic tail. Microscopic examination showed a spindle cell neoplasm arranged in a vague fascicular fashion with moderate nuclear pleomorphism, geographic necrosis, and frequent mitotic figures (15 per 10 high power fields). Fifteen lymph nodes were negative for metastasis. The tumor was confined to the pancreas grossly and microscopically.

Immunohistochemical stains showed the neoplastic spindle cells to be positive for TLE1 (diffuse) and S100 (patchy), while negative for SOX10, CD117, DOG1, desmin, actin, MyoD1, ERG, STAT6, and ALK1. In addition, H3K27me3 showed loss of nuclear expression. Next generation sequencing (NGS) revealed gene mutations in NF1, TP53, PIK3CA, and PTEN, and copy number losses involving CDKN2A and CDKN2B. Genome-wide DNA methylation analysis was performed which revealed copy number losses of CDKN2A/B and gains of PTCH1 and MDM2. However, the Sarcoma DNA Methylation Classifier did not provide any diagnostic matches. Overall, the morphologic features, loss of H3K27me3 expression, presence of NF1 and TP53 mutations, and copy number losses in CDKN2A/B supported a diagnosis of high-grade MPNST. The patient has been followed clinically without adjuvant therapy.

Results (if a Case Study enter NA)

N/A

Conclusion

We report an extremely rare case of MPNST of the pancreas with molecular confirmation.
Congenital Appendiceal Atresia: An Extremely Rare Disorder Presenting with Acute Abdomen
Authors: Asad M , ANAND S , Sieber S C
Published: October 2024

Introduction/Objective

Congenital malformations of the appendix are extremely rare and difficult to diagnose preoperatively. One of those anomalies include congenital appendiceal atresia (CAA) which mimics acute appendicitis and is usually ignored in the differentials of acute abdomen. Herein, we present a case study of congenital appendiceal atresia associated with periappendicitis.

Methods/Case Report

A 62-year-old female with past history of diverticulitis presented with complaints of crampy, diffuse and progressive lower abdominal pain and nausea for two days. She denied fevers, chills or change in bowel movements. Physical examination revealed vitally stable patient with soft, non-distended and tender abdomen in bilateral lower quadrants, worse on the right side and showing positive rebound test. Her complete blood count and chemistry were within normal limits. A computerized tomography arterial portography (CTAP) scan with contrast demonstrated inflammatory stranding around the appendix without abscess, concerning for acute appendicitis. She then underwent laparoscopic appendectomy. Grossly, the appendix consisted of a cylindrical portion of yellow-pink fatty tissue covered by peritoneum measuring 6.2 x 3.3 x 0.5 cm. The peritoneal surface displayed patchy fibrinous exudates. Sectioning revealed yellow adipose tissue with no identifiable appendix. Microscopically, the entire specimen demonstrated a poorly formed, mainly fatty appendix without a discernible lumen or submucosal lymphoid tissue. There were scattered sparsely distributed non-continuous bundles of smooth muscle (muscularis propria) at the periphery, which were highlighted by desmin and trichrome stains. This atretic appendix, mesoappendix and peritoneal covering were acutely inflamed. The final diagnosis was poorly formed, acutely inflamed fatty appendix consistent with congenital appendiceal atresia with accompanying acute periappendicitis.

Results (if a Case Study enter NA)

NA

Conclusion

This case would add to the very limited existing literature for congenital appendiceal anomalies and highlight the importance of thorough surgical intraoperative abdominal exploration and submission of the entire specimen for microscopic examination in order to render a definitive diagnosis.
A 34-year-old woman with mucolipidosis type IV predisposing to a neuroendocrine tumor in the gastric fundus
Authors: Snow M , del Portillo A
Published: October 2024

Introduction/Objective

Mucolipidosis type IV (MLIV) is a lysosomal storage disorder with a gastric phenotype. Patients develop achlorhydia and compensatory hypergastrinemia, with pathology showing vacuolated parietal cells with lysosomal inclusions. MLIV is caused by mutation of TRPML1, a lysosomal membrane calcium channel required for trafficking proton pumps to the apical surface in parietal cells. We report the first case of MLIV predisposing to a neuroendocrine tumor (NET). This novel finding could impact management of patients with this disease, who may require frequent monitoring for NETs. We also show that immunohistochemistry for TRPML1 and H+/K+ ATPase can be used in conjunction to identify gastric MLIV. We hope that our updated immunohistochemical tools can aid in diagnosis of this disease.

Methods/Case Report

34-year-old woman with MLIV requiring endoscopic resection for an incidentally discovered gastric polyp. Pathology showed Grade 2 NET invasion into submucosa (pT1). Background mucosa showed markedly vacuolated parietal cells, ranging from unilocular to multilocular with up to 20 vacuoles per cell. We stained the patient’s and a control stomach with antibodies against the TRPML1 and H+/K+ ATPase proteins. The H+/K+ ATPase antibody highlighted healthy parietal cells in the control stomach with strong cytoplasmic signal, but strikingly outlined lysosomal inclusions in MLIV parietal cells. TRPML-1 antibody showed cytoplasmic staining in parietal cells in the control. However, TRPML-1 staining showed markedly decreased signal in the patient and nuclear staining, possibly representing mislocalization.

Results (if a Case Study enter NA)

NA

Conclusion

We present the first case of MLIV predisposing to a NET in the stomach. NETs have potential for metastatic spread with subsequent mortality risk. Clinicians should maintain suspicion for NET development in this population, and protocols for frequent surveillance should be considered.

This is also the first report using immunohistochemistry for TRPML1 and H+/K+ ATPase in combination to identify affected parietal cells in MLIV. Possibly, these tools can be used in the future by pathologists to diagnose MLIV.
Duodenal Adenocarcinoma Arising from Brunner’s Glands, A Rare Case Report
Authors: Arumugam S
Published: October 2024

Introduction/Objective

Malignancies arising from the Brunner’s glands in duodenum are exceedingly rare with very few cases reported in the literature. Here, we reported a case of duodenal adenocarcinoma of Brunner’s gland origin that obstructed duodenum and extended to involve the pancreatic head.

Methods/Case Report

A 48-year-old woman came to the Emergency Department of our hospital with epigastric and right upper quadrant abdominal pain. CT imaging demonstrated a heterogeneously enhancing 8.4 x 5.4 x 6 cm mass involving the duodenal lumen, wall, and pancreatic head. An endoscopic ultrasound showed a large fungating, infiltrative, and ulcerative mass in the second portion of the duodenum distal to the ampulla but not involving it. The pancreatic and common bile ducts were uninvolved. Her endoscopic ultrasound biopsy was positive for adenocarcinoma. CA19-9 levels were normal. The patient received chemotherapy with subsequent Whipple procedure. Gross examination revealed an exophytic, tan-white mass with the epicenter in the duodenal wall obstructing the duodenal lumen and extending to involve the pancreatic head inferiorly. The mass was predominantly solid with a few small mucus cysts. Light microscopy demonstrated moderately differentiated adenocarcinoma with prominent necrosis and inflammation. There are intestinal-type, gastric-type and indeterminate types of epithelia in the carcinoma. There are areas in the duodenal wall where a continuous transition from benign Brunner’s glands to dysplastic glands and then to adenocarcinoma is present. Neither adenoma in the overlying duodenal mucosa nor abnormalities in the pancreatic parenchyma is observed. Immunohistochemical stains showed that the neoplastic cells are positive for CAM 5.2, AE1/AE3, and CK7, while only patchy positivity with CK20 and CDX2. Taken together, a diagnosis of duodenal adenocarcinoma arising from Brunner’s glands was rendered.

Results (if a Case Study enter NA)

N/A

Conclusion

More cases are needed in order to establish standard treatment guidelines and determine prognostic factors.
Leiomyomas of the Gastrointestinal Tract: A Clinicopathologic Review
Authors: Apdik T , Musharraf S , Gattuso P , Reddy V , Cheng L , Furci F
Published: October 2024

Introduction/Objective

Leiomyomas are benign smooth muscle tumors that can be found anywhere along the gastrointestinal tract (GIT). We undertook a retrospective study to investigate the incidence of GIT leiomyomas and to gain better understanding of their clinicopathologic characteristics.

Methods/Case Report

The surgical pathology files at our institution were searched for GIT leiomyomas encountered between 07/1994 and 12/2023. The clinical and histopathological findings were recorded.

Results (if a Case Study enter NA)

74 leiomyomas were identified in various GIT locations, including esophagus (8), stomach (20), duodenum (3), colon (37) and rectum (6). There were 40 females and 34 males, with an average age of 61.5 years.

Esophageal leiomyomas showed a mean size of 2.2 cm. 5/8 patients had synchronous adenocarcinomas of gastroesophageal junction and 1/8 patient had synchronous squamous cell carcinoma of esophagus.

Gastric leiomyomas showed a mean size of 2.0 cm. 6/20 patients had synchronous and 4/20 patients had metachronous GIT cancers. 2/6 patients who had leiomyomas with synchronous GIT cancers also presented with gastrointestinal stromal tumors (GIST).

Duodenal leiomyomas showed a mean size of 0.7 cm. 1/3 patient had synchronous pancreatic adenocarcinoma. Colonic leiomyomas showed a mean tumor size of 0.6 cm. 2/37 patients had synchronous and 6/37 patients had metachronous GIT cancers.

Rectal leiomyomas showed a mean tumor size of 0.9 cm. 1/6 patient had metachronous non-GIT sarcoma. Adenomatous polyps coexisted with 10/37 colonic leiomyomas, 2/6 rectal leiomyomas and 1/20 gastric leiomyoma. Immunohistochemical stains (αSMA, Desmin, CD117, DOG-1, CD34) were consistently utilized in diagnosis to exclude GIST.

Conclusion

Leiomyomas were most frequently found in the colon (50.0%), followed by the stomach (27.0%). Esophageal and gastric leiomyomas showed larger sizes (averaged 2.2 and 2.0 cm respectively) than duodenal, colonic, and rectal counterparts (averaged 0.7, 0.6, and 1 cm, respectively). This suggests an association between tumor locations and clinical features.

Synchronous malignancies occurred in 20.2% of cases, mainly gastroesophageal/colonic adenocarcinomas. Metachronous malignancies were noted in 14.8% of cases. Given the high incidence of synchronous/metachronous malignancies (35.1%) in the gastrointestinal tract, close clinical surveillance is warranted for these patients.
Mediastinal Teratoma with Angiosarcomatous Overgrowth in a Background of Vasculogenic Mesenchymal Tumor
Authors: Graham S M , Pham J M , Cao T , Hamza A
Published: October 2024

Introduction/Objective

Vasculogenic mesenchymal tumor refers to neoplastic reiteration of embryonic vasculogenesis. It is most commonly associated with nonseminomatous germ cell tumors of the mediastinum, in particular yolk sac tumor. In rare instances these lesions progress to angiosarcoma. Herein, we describe a case of angiosarcoma in a background of vasculogenic mesenchymal tumor in the setting of a mediastinal teratoma.

Methods/Case Report

A 33-year-old male, with a past medical history of anxiety, and right orchiectomy for testicular torsion, presented with shortness of breath, chest pain, and left arm swelling. Imaging studies demonstrated a mediastinal mass. Biopsy of the mass showed a germ cell tumor most compatible with a teratoma in the limited specimen. The patient received two rounds of chemotherapy and additional treatments were discontinued due to poor tolerance. Subsequent imaging showed continued increase in the size along with mass effect causing moderate to severe compression of the superior vena cava. Subsequently, the patient underwent resection of the mass. Grossly the mass was predominantly encapsulated with areas of capsular disruption. Sectioning revealed heterogeneous cut surfaces with fleshy, cystic, and necrotic areas. Morphologically the tumor was composed predominantly of teratomatous elements with areas of anastomosing atypical vascular channels within a hypocellular stroma suggestive of vascular genic mesenchymal as well as areas reminiscent of Masson lesion. Focally within these areas were malignant spindle cell proliferations compatible with angiosarcoma. The patient had an elevated AFP; however, no yolk sac tumor component was identified after thorough sampling. Final diagnosis of teratoma with angiosarcoma in a background of vasculogenic mesenchymal tumor was rendered after expert consultation.

Results (if a Case Study enter NA)

NA

Conclusion

Somatic-type malignancy and sarcomatous overgrowth are known to occur in mediastinal germ cell tumors; however, classification of the sarcomatous overgrowth can be challenging. Vasculogenic mesenchymal tumor is an exceedingly rare sarcomatous overgrowth that can rarely progress to angiosarcoma.
Weakly supervised deep learning for diagnosis of prostate cancer after radical prostatectomy: a population- based, multicenter study
Authors: Xiao Y , Mai Z , Yan W
Published: October 2024

Introduction/Objective

The pathological diagnosis of prostate cancer after radical prostatectomy (RP) is a challenging and time-consuming process. Artificial intelligence has the potential to enhance this situation significantly. Our study aimed to assess the efficacy of weakly supervised deep learning, specifically focusing on practical diagnostic tasks for RP specimens.

Methods/Case Report

We obtained slices from clinical centers across four regions in China. The model was developed based on a multiple instance learning framework. We evaluated the model’s predictive accuracy, covering both slice-level and lesion-level diagnoses. Additionally, we investigated lesion localization using attention visualization. Slice-level diagnosis included prostate cancer detection and Gleason grading, while lesion-level diagnosis involved recognizing index lesions and non-index lesions.

Results (if a Case Study enter NA)

The study involved 13,245 slides from 304 patients. The area under the curve values in four validation sets ranged from 0.921 (95% CI 0.913–0.930) to 0.964 (95% CI 0.959–0.968). Regarding Gleason grading, the model demonstrated quadratic Weighted Kappa values of 0.748 and 0.720 for internal and external validation, respectively. The model predicted 1,683 (35.3%) positive and 3,081 (64.7%) negative slices in all validation sets. The median area of index lesions and non-index lesions was 92.6mm2 (IQR: 54.2–130.0mm2) and 3.5mm2 (IQR: 1.4–10.9mm2) (p<0.001), respectively. The model accurately predicted index lesions in all cases for three validation sets. Furthermore, the model achieved 100% accuracy in predicting slides with the maximum tumor area for index lesions in two validation sets. In visual assessment, 200 randomly selected slices predicted as true positive demonstrated that the model could identify 97.5% (195/200) of the index lesions.

Conclusion

The weakly supervised deep learning model demonstrated remarkably high diagnostic and localization capabilities in identifying index lesions within RP specimens. This targeted approach would effectively alleviate the diagnostic workload associated with pathology assessments for prostate cancer.
Leiomyoma with bizarre nuclei occurring post hysterectomy mimicking malignancy: a rare case report
Authors: Bian F , Feng Y , Angel J
Published: October 2024

Introduction/Objective

Leiomyoma with bizarre nuclei (LBN), also known as symplastic leiomyoma, represents a rare subtype of benign uterine smooth muscle neoplasm. Histologically, it is characterized by significant cytological atypia in a typical leiomyoma background with rare mitoses and without tumor necrosis.

Methods/Case Report

We report a case of a 48-year-old woman, status post hysterectomy for symptomatic fibroids, with imaging showing multiple contiguous pelvic masses extending from the pelvis to the upper abdomen and displacing the colon laterally and small bowel posteriorly. The findings were highly suspicious for ovarian malignancy. A bilateral salpingo-oophorectomy and a partial colectomy were performed with tumor debulking and omentectomy. Grossly, multiple well-circumscribed soft masses ranging in size from 1.5-16 cm, in contiguity with pericolonic mesentery with a smooth fleshy cut surface and cystic changes were found. Bilateral ovaries were unremarkable.

Microscopically the larger masses were composed of spindle cells with bizarre nuclei throughout, while smaller masses showed foci of bizarrely shaped-spindle cells with bizarre nuclei in a background of a typical leiomyoma. Mono- and multinucleated cells with smudged chromatin were also seen. The mitotic index was low confirmed with a low Ki-67 proliferation index (< 5%). Immunohistochemical stainings showed that the neoplastic cells were positive for desmin, SMA, and caldesmon; and negative for CD10, with a wild type p53 expression. Fumarate hydratase immunostain was retained. MDM2 amplification was not detected by FISH. The morphology and immunohistochemical findings were compatible with LBN.

Results (if a Case Study enter NA)

NA

Conclusion

In summary, this is a rare and challenging case of multiple LBN developed years post hysterectomy and clinically mimicking a malignancy.