bluuebunny/crossref_metadata_2025 huggingface dataset:
Can cholesterol be too low? A retrospective correlation of cholesterol lab values to other markers of cardiovascular disease risk
Authors: Petersen P , Chambliss A
Published: October 2021

Introduction/Objective

Most recommendations for lipid panel reference ranges are one-sided (desirable total cholesterol is <200 mg/dL, optimal LDL cholesterol [LDL-C] is <100 mg/dL). However, recent studies suggest risks for cardiovascular diseases or mortality at very low cholesterol values. In this retrospective study, we investigated the association between lipid panel results and surrogate markers of cardiovascular disease to test the hypothesis that very low cholesterol levels are associated with increases in cardiovascular risk.

Methods/Case Report

Patients with lipid panels reported from April 2020-March 2021 at LAC+USC Medical Center were included. Lipid panels (total cholesterol, LDL-C, HDL-C, triglycerides) and laboratory results representing risk factors for cardiovascular disease (troponin T (TnT), NT-pro brain natriuretic peptide (BNP), hemoglobin A1c (HbA1c), high sensitivity C-reactive protein (CRP)) were collated. Lipid panel values were compared against the percentage of patients with non-optimal laboratory results for the cardiovascular risk markers.

Results (if a Case Study enter NA)

Decreasing total cholesterol levels vs. the percentage of patients with high TnT or BNP showed a U-curve with a nadir at 200-240 mg/dL (elevated TnT: 15%, BNP: 49%) and further increased with lower cholesterol levels <60 mg/dL (TnT: 56%, BNP: 92%); HbA1c (U-curve, nadir: 160-180 mg/dL); and CRP (90% at cholesterol <60 mg/dL; 43% at 220-240 mg/dL). Decreasing HDL-C against all markers of cardiovascular disease demonstrated a continued downtrend below optimal HDL-C levels. Decreasing LDL-C vs. the percentage of high TnT showed a U-curve with a nadir at 120-140 mg/dL; BNP (uptrends in the optimal range of LDL-C); HbA1c (U-curve, nadir: 90-100 mg/dL); and CRP (uptrends with decreasing LDL-C). TnT and BNP decreased with increasing triglycerides, while HbA1c increased with increasing triglycerides. Data points (TnT: n > 5,000; BNP: n > 3,000; HbA1c: n > 29,000; CRP: n > 4,500).

Conclusion

Very low concentrations of total cholesterol and LDL-cholesterol are associated with elevated markers of cardiovascular risk. Laboratories may wish to consider incorporating low ends to total cholesterol and LDL-cholesterol reference ranges.
Impact of Removing Race Adjustment When Estimating GFR on Chronic Kidney Disease Staging
Authors: Cai C , Sahor F , Wilson B , Veeramachaneni T , Hashim I
Published: October 2021

Introduction/Objective

Determination of glomerular filtration rate (GFR) is essential in assessment of kidney function, particularly in patients with chronic kidney disease (CKD). Formulas were developed to calculate estimated GFR (eGFR), as direct measurement is cumbersome and not amenable to routine monitoring. CKD-EPI is the most widely used formula for eGFR, using parameters of serum creatinine, gender, race, and age. A race adjustment was added from an unfounded assumption that Black patients have more muscle mass, increasing their eGFR by about 16%. There is concern on the impact of “correcting” for Black race on patient management, utility of eGFR, and its possible contribution to healthcare disparities. This study examined the impact of eliminating race adjustment from the CKD- EPI formula on CKD staging in patients at a large safety-net hospital in an academic medical center.

Methods/Case Report

80090 serum creatinine values from 56676 adult patients (31.4% Black, 67.5% female, median age 51 yrs) were collected from the electronic medical record (Epic, Verona, WI) over a 16-month timeframe. Values were excluded if they lacked age, gender, self-identified race, or serum creatinine. eGFR was calculated using the CKD-EPI equation with and without race modifier, and CKD staging was performed using 2012 Kidney Disease: Improving Global Outcomes guidelines.

Results (if a Case Study enter NA)

In our cohort, only 50.8% of Black patients are in CKD1, indicative of no CKD, compared to 67.9% of non-Black patients. Given that these two cohorts are demographically similar, this shows a discrepancy in kidney function even before removing the race adjustment. After removal of the race modifier, 28.1% of Black patients were reclassified into a more severe CKD stage. The most restaging occurred from CKD3A to 3B (39%).

Conclusion

Many Black patients in our study were reclassified to a more severe CKD stage, with the highest percentage of patients restaged to CKD3B, which would have attracted clinical attention for nephrology referral. We recommend removal of the race adjustment in eGFR, given its basis in the incorrect belief in biological differences between races. It perpetuates systemic racism and discrimination in healthcare, and its removal will provide more equitable care and reduce healthcare disparities. Future studies should examine the increase in resources required to provide adequate medical care to patients who will be placed into a more severe CKD stage.
POC Programs: A Brief Survey on Critical Value Thresholds, Instrumentation, Repeat Testing, and Training Documentation
Authors: Castle B , Vonlinsowe E , Cook B , Hayward J , Sharma G
Published: October 2021

Introduction/Objective

Across the United States, Point of Care (POC) programs oversee glucometer testing and are often expected to enforce thresholds for critical values, as well as provide guidance on repeat testing. Additionally, POC must track training and ongoing competency assessments of glucometer operators. Our aim was to survey POC across North America to capture the current state of variation in these POC functions, and identify opportunities for standardization.

Methods/Case Report

In July of 2021, an online survey was created on www.surveymonkey.com and distributed via the POC listserv of the American Association for Clinical Chemistry (AACC). The survey listed nine questions regarding instrumentation, threshold levels for critical-high and critical-low, policies on repeat testing, and practices around documentation and record retention.

Results (if a Case Study enter NA)

Of the 63 responses received, almost all (95.2%, n=60) indicated that their institution defines glucometer critical value thresholds. Of these, the most common threshold for critical-high was 400 mg/dL (44.4%, n=28) and for critical-low was 50 mg/dL (39.7%, n=25). A majority (55.5%, n=35) of programs require repeat testing of results that exceeded critical limits. The most popular POC result management software (50.8%, n=32) was RALS (Abbott Diagnostics, Chicago, IL) and the most popular glucometer (56%, n=23) was Roche Accu- Chek Inform II (Roche Diagnostics, Basel, Switzerland). Regarding institutions that disclosed training and competency documentation practices (93.7%, n=59), a majority (57.6%, n=34) used online-only storage, followed by hybrid online- paper storage (32.2%, n=19), and paper-only storage (10.2%, n=6).

Conclusion

Our brief survey has uncovered variations and insights that should raise queries on the feasibility of standardized critical value thresholds, as well as uniform recommendations for retesting critical values. We observed widespread adoption of middleware, as well as online record-keeping. We hope that our findings will trigger further discussions and follow-up studies by other researchers in the POC field.
Vitamin D deficiency Crisis in Egypt
Authors: Abdelmonem M , Elhusseny A , Wasim H , Shedid M , Boraik A S
Published: October 2021

Introduction/Objective

Vitamin D deficiency is a worldwide health problem. Even with the latest medical technology worldwide, vitamin D deficiency is still an ignored epidemic. More than a billion people globally are vitamin D deficient or insufficient. Vitamin D is essential for strong bones as it is responsible for the absorption of calcium, magnesium, and phosphate in the human body. It is essential for building the human immune system and legalizing cell growth. Vitamin D deficiency can result in muscle vulnerability, pain, tiredness, and depression. Severe Vitamin D deficiency can cause Rickets disease.

Objectives

This study aims to predict the percentage of vitamin D deficiency in Egypt.

Methods/Case Report

A total of 498 subjects were enrolled in this study from the Cairo region in Egypt; 203 (41%) were male, 260 (52%) were female, and 35 (7%) were children with a median age of 36.2 years, 36.7 years and 5.3 years respectively. A fully automated chemiluminescence immunoassay analyzer (CLIA) was used to measure Vitamin D in all subjects’ specimens.

Results (if a Case Study enter NA)

The overall prevalence of Vitamin D deficiency was 90.09%. Among the 498 patients, 453 patients (90.09%) were Vitamin D deficient (less than 30 ng/ml), while 45 patients (9.03%) of the patients were within the normal Vitamin D range. It was observed that 192 patients (94.54%) of males,237 patients (91.15%) of females, and 11patients (31.42%) of children were Vitamin D deficient. Furthermore, 11 patients (5.41%) of males, 23 patients (8.84%) of females, and 23 patients 65.71% of children are within the normal Vitamin D range.

Conclusion

Our findings reveal a significant frequency of vitamin D deficiency in Egypt. Inadequate sun exposure, Insufficient dietary calcium, gastrointestinal disorders, renal diseases, and liver diseases contribute to vitamin D deficiency. We recommend that the Egyptian Health ministry launch an awareness campaign for the severe Vitamin D deficiency in Egypt.
Pancreatic Metastasis from Breast Cancer: A Clinicopathological Study of Four Cases by Fine Needle Aspiration
Authors: Chen M Y , Xu Y
Published: October 2021

Introduction/Objective

Pancreatic metastases are rare, and the most common neoplasms are carcinomas from the kidney, lung, and breast.

Methods/Case Report

We present four cases of breast ductal carcinoma in patients with metastases to the pancreas diagnosed by endoscopic ultrasound guided fine needle aspiration (EUS-FNA). The four female patients ranged from 37 to 64 years in age. Three patients had breast cancer histories, ranging from 1 to 21 years. The patient without cancer history was found to have breast mass also. Two patients had triple negative breast ductal carcinoma. The breast cancer biomarkers on the other two patients showed ER+, PR-, Her2 3+, and ER-, PR-, Her2 3+, respectively. Two patients had histories of metastatic breast cancer involving bone, liver and brain. All patients presented with symptoms associated with pancreatic mass. By imaging, solitary pancreatic head masses were found in three patients, ranging from 2.4 to 3.7 cm. One patient had two pancreatic masses (head, 2.6 cm; body, 2.9 cm). EUS-FNAs targeting the pancreatic head masses were performed on the four patients. Cell blocks were available for all except one (due to limited cells), which had subsequent histology diagnosis.

Results (if a Case Study enter NA)

FNAs demonstrated loosely cohesive tumor cells with enlarged, hyperchromatic nuclei, occasional prominent nucleoli, and occasional intracytoplasmic vacuoles, morphologically and immunohistochemically (CK7 +, GCDFP-15 focally +, CA19.9 -, biomarkers similar to primary tumors) consistent with breast primary. Follow-up revealed three patients expired one month, 2.5 years, and 5 years post-diagnosis, respectively. One patient without prior cancer history has been stable for 7 years.

Conclusion

Our study demonstrates the clinicopathological features of four cases of breast ductal carcinoma metastasized to the pancreas. We emphasize the important role of EUS-FNA for diagnoses of pancreas metastases. The finding of two of four cases with triple negative biomarkers may raise the importance of close follow-up in these patients for pancreatic metastasis.
Cytomorphologic Features of Extramammary Paget’s Disease of The Vulva in a patient with history of Squamous Cell Carcinoma of The Cervix, Status Post Chemoradiation and Neoadjuvant Therapy. The Importance of Basic Principles
Authors: Duhoki D , Gonzalez M F
Published: October 2021

Introduction/Objective

Extramammary Paget disease (EMPD) is a rare neoplasm commonly affects postmenopausal women. It usually presents in the anogenital area where apocrine sweat glands are abundant, most commonly in the vulva. The disease is characterized by slow grow and high local recurrence rates. Clinically, EMPD present as well demarcated erythematous lesion or plaques that may ulcerated. Microscopically, it shows a group of atypical cells with abundant clear cytoplasm and nuclear pleomorphism.

Methods/Case Report

Here in we present a 58-year-old female with history of vulvar intraepithelial neoplasia III (VIN III) status post wide local excision, and poorly differentiated squamous cell carcinoma status post radical hysterectomy and bilateral salpingo-oopherectomy and chemoradiation who presented for perineal pain, itching and discomfort. She also noticed skin changes on her left labia without bleeding or discharge. Punch biopsies of the vulva and periurethral areas revealed acanthosis of the epidermis with intraepidermal scattering of single or clusters of large cells with round/ovoid nuclei and abundant clear cytoplasm. The cells are positive for p16, CK19, CK7, PAX8 supporting the diagnosis of EMPD without evidence of dysplasia. The concurrent PAP smear shows hypercellular specimen composed of hyperchromatic fragments of tissue with high nuclear-to-cytoplasmic rations, and apoptotic bodies. The presence of intracytoplasmic mucin and the tridimensionality of the fragments supported the diagnosis of adenocarcinoma. The HPV testing was positive for HPV-16.

Results (if a Case Study enter NA)

N/A

Conclusion

This study compares the histological and cytomorphological features of EMPD with high-grade squamous intraepithelial lesion (HSIL), since the molecular pathways, precursor lesions, etiologic associations, staging, clinical treatment, and prognosis differ substantially and may have a significant clinical impact for the patient’s treatment.
Cytology Detects Endobronchial Metastasis from Appendiceal Signet-Ring Cell Carcinoma in the Absence of Radiographic Lung Masses: A Case Report
Authors: Taylor B W , Hummel K , Xu Y
Published: October 2021

Introduction/Objective

Endobronchial metastasis (EBM) is uncommon, with a reported prevalence of 2% in cases of non-lung primary malignancies. The most frequently observed carcinomas in EBM are from breast, colon, and renal origins. We present a rare case of endobronchial metastasis from a primary tumor of the appendix without lung masses by computed tomography (CT).

Methods/Case Report

An 83-year-old woman with signet-ring cell carcinoma of the appendix underwent right hemicolectomy and chemotherapy. Two years later, she returned with intractable nausea and vomiting, and respiratory distress. CT of the chest demonstrated diffuse bilateral pulmonary opacities without lung masses. CT of the abdomen showed peritoneal carcinomatosis. Cytology of ascitic fluid displayed metastasis of the patient’s known appendiceal tumor. Bronchoscopy found significant friable debris appearing to be tumor tissue and occluding multiple bronchioles in the right lung. A bronchoalveolar lavage (BAL) specimen from the right lung was sent for liquid-based cytology, which revealed a few atypical cells with eccentric nuclei and intracytoplasmic vacuoles, abundant macrophages, degenerated mixed inflammatory cells, and scattered bronchial epithelial cells. Cell block demonstrated signet-ring cells mimicking macrophages and infiltrating into small fragments of bronchiolar wall. The signet-ring cells were morphologically similar to those found in the ascitic fluid and the patient’s primary tumor, and were highlighted by mucicarmine stain and immunohistochemical stains for CDX-2 and CK20, but not CK7.

Results (if a Case Study enter NA)

N/A

Conclusion

Collectively, the findings supported the diagnosis of endobronchial metastasis of signet-ring cell carcinoma from the lower gastrointestinal tract, i.e. the patient’s known appendiceal primary. Our case demonstrates a rare endobronchial metastasis of a primary neoplasm of the appendix, an important diagnostic consideration when evaluating respiratory distress in patients with such cancer histories. We have described the significant role of BAL cytology to uncover endobronchial metastases without lung masses by CT, and illustrated the finding of signet-ring cells mimicking macrophages in a BAL cytology specimen.
Cutaneous Angiomyolipoma (Angiolipoleiomyoma): Case Report and Review of Literature with Emphasis on Nomenclature
Authors: Brudnik R , Shurbaji M S , Vellila R E
Published: October 2021

Introduction/Objective

Cutaneous angiomyolipomas (AML) are rare lesions that have morphological similarities to renal AML, but appear to be biologically distinct.

Methods/Case Report

We report the case of a 69-year-old man who presented with a slowly enlarging nodule on the dorsum of the right hand that was painful upon wrist flexion and is slightly tender to palpation. A ganglion cyst was clinically suspected, and the lesion was excised. Microscopically, this was a well-circumscribed nodule with a thin fibrous capsule that was highlighted by a trichrome stain. The lesion was composed of thick-walled blood vessels surrounded by bundles of smooth muscles that intermingled with adipose tissue. Smooth muscle actin immunostain highlighted the smooth muscles, but HMB-45 was negative. There was no atypia, and no mitoses. A diagnosis of “cutaneous angiomyolipoma” was made.

Results (if a Case Study enter NA)

NA

Conclusion

A review of the limited number of published cases showed that unlike renal AML, this lesion is not associated with tuberous sclerosis, is negative for melanocytic markers, and shows male-predominance, suggesting that the two morphologically similar lesions are biologically unrelated. The 2018 WHO classification of skin Tumors does not list this entity, so nomenclature is not standardized. Some authors suggested that these are simply angioleiomyomas with prominent adipose tissue, but the female predominance of angioleiomyoma makes this unlikely. Others have recognized this as a distinct entity and described it as an “angiolipoleiomyoma”, to distinguish it from renal AML. We now advocate for the latter approach to avoid confusion with renal AML. Otherwise, the prefix of “cutaneous” should always be used in the diagnosis to highlight this distinction.
Biphasic Sarcomatoid Sweat Gland Carcinoma With Ductal Epithelial And Spindled Myoepithelial Cell Components (Malignant Mixed Tumor Of Skin)
Authors: Chiu R , Tran T , Miranda-Taylor M , Bamdad S , Jia Y , Crabtree M , Cornford M , Yap C , Peng S
Published: October 2021

Introduction/Objective

Sweat gland carcinomas are a group of malignant skin adnexal tumors that are difficult to diagnose due to their rarity, wide morphologic variation, and limited literature on diagnosis and classification. These tumors may appear bland and morphologically resemble benign skin adnexal tumors, or may appear poorly differentiated and mimic metastatic carcinoma especially from a breast primary. Biphasic sweat gland carcinomas are an even rarer entity, with only few cases reported in literature, and have been described to consist of a well- differentiated ductal epithelial component and a poorly differentiated, sarcomatoid, spindle cell component.

Methods/Case Report

Our case report describes a 53 year old female referred to our institution for diagnosis of an excised skin lesion of the right upper arm, which had been slowly growing for 8 years. The histology revealed a biphasic malignant neoplasm involving the dermis and subcutis. The tumor consisted of an epithelial cell component with glandular and squamoid morphology and positive for CK5/6, CK7, and CAM5.2, and a spindled myoepithelial cell component with sarcomatoid morphology and positive for S100, vimentin, and p63. Stains for CK20, ER, PR, PAX8, CEA, and TTF1 were negative. The histological and clinical findings favored a primary skin adnexal tumor, rather than a metastatic lesion.

The patient underwent wide local excision of the lesion given that margins of the original excision were indeterminate. The histology of this re-excision demonstrated the same biphasic tumor with ductal epithelial and sarcomatoid myoepithelial cell components positive for the same stains. Although margins were negative in this re-excision, 3-4 months later, the patient developed dyspnea with multiple new pulmonary and hilar masses discovered on imaging, and new-onset headache with a frontal lobe mass discovered on brain imaging. These masses were biopsied/resected, and revealed to be metastases of the original cutaneous tumor positive for the same markers.

Results (if a Case Study enter NA)

NA

Conclusion

This case report describes a rare, diagnostically challenging case of a biphasic sweat gland carcinoma with ductal epithelial and sarcomatoid myoepithelial cell components, which demonstrated aggressive behavior with distant metastasis. These tumors are a clinicopathological quandary given their rarity and the paucity of literature on their characterization.
Immunohistochemistry Aids in the Diagnosis of Blastic Plasmacytoid Dendritic Cell Neoplasm in a Patient with Multiple Cutaneous Plaques and Nodules
Authors: Kaur H , Reyes-Barron C , Scott G
Published: October 2021

Introduction/Objective

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a rare hematologic malignancy of plasmacytoid dendritic cell precursors with an estimated incidence of 0.04 cases per 100,000 in the US. Given the cutaneous tropism of BPDCN, it should be differentiated from other CD56+ hematopoietic neoplasms with skin involvement such as CD56+ AML, extranodal NK/T-cell lymphoma, and other T-cell lymphomas.

Methods/Case Report

A 71-year-old male presented to the emergency department with asymptomatic, pink- violaceous plaques/nodules on the trunk for 3 months. One month prior, a dermatologist diagnosed epidermal inclusion cysts that were left untreated. The nodules progressed and a course of steroids prescribed by a primary care physician provided short term improvement before the lesions flared again. Review of systems and vitals were normal. Biopsies of representative lesions sent for histologic examination showed a diffuse dermal infiltrate of small to medium atypical cells with irregular nuclear contours, fine chromatin, one to several nucleoli and scant cytoplasm. Immunohistochemistry showed these cells were positive for CD2, CD4, CD56 and CD45 with strong expression of BCL2 and focal CD123. The cells were negative for CD3, CD20, CD79a, CD8, CD30, ALK-1, MUM-1, CD10, Cyclin- D1, C-MYC, EBER, BCL6, Langerin, Granzyme, TIA1, CD68, CD163, MPO, and Lysozyme. The histology and immunoprofile were consistent with BPDCN. A bone marrow biopsy showed cells with similar morphology and staining pattern, including expression of CD123.Treatment with chemotherapy and Tagraxofusp, was initiated. Within a week, the patient showed near resolution of cutaneous lesions. Repeat bone marrow aspirate and flow cytometry a month later showed no malignant cells.

Results (if a Case Study enter NA)

NA

Conclusion

We present this case as a rare hematologic malignancy with a challenging clinical and histopathologic diagnosis. The histologic findings suggested either a high grade myeloid or lymphoid malignancy. The combination of CD3-/CD56+/CD4+/CD123+ in the lesional cells helped establish the diagnosis of BPDCN, allowing for prompt treatment.
A rare case of genital porokeratosis clinically misdiagnosed as lichen planus
Authors: Emechebe D , Mendoza R P , Heilman E
Published: October 2021

Introduction/Objective

Porokeratosis is a clonal disorder of keratinization characterized by atrophic patches surrounded by a histologically distinctive hyperkeratotic ridge-like border called the cornoid lamella. Porokeratosis occurring on the genital area is considered a rare entity and much more unusual when in isolated form

Methods/Case Report

This is a case of a 54-year old man who presented with a penile lesion that has been present for 10 years, unchanged, non-bleeding and non-pruritic. There was no history of genital ulcer or inguinal swelling, neither any history of sexual promiscuity. The patient has a history of basal cell carcinoma on the right nasal area managed with Mohs surgery and scalp actinic keratoses treated with liquid nitrogen. On examination, there was a solitary 6-mm red linear macule with collarette of white scale on the corona of the penis. There was no similar lesion seen on other body parts. His blood investigations, including venereal disease research laboratory test (VDRL) and HIV screening, were negative. The initial clinical diagnosis was lichen planus, and triamcinolone was administered for three months with minimal benefit. This failed steroid management prompted a shave biopsy

Results (if a Case Study enter NA)

Histologic sections showed a column of hyperkeratosis arising from the epidermis (cornoid lamella) with absent granular layer and dyskeratotic cells beneath the cornoid lamella, confirming the diagnosis of porokeratosis limited to the genitalia

Conclusion

Porokeratosis is considered a pre-malignant condition based on clonal proliferation, dyskeratotic cells, abnormal keratinocyte maturation and p53 overexpression. Malignant progression to Bowen’s disease and squamous cell carcinoma has been documented in 6.9 to 30% of cases.
An Uncommon Case of Colonic Neuroendocrine Carcinoma with Scalp Metastasis
Authors: Karimi S S , Braniecki M
Published: October 2021

Introduction/Objective

Neuroendocrine neoplasms of the colon account for <1% of all colorectal malignancies. While visceral metastasis of neuroendocrine neoplasms is commonly observed, cutaneous distant metastasis has infrequently been reported and correlates with an advance stage and progression of disease. To our knowledge, there have been only 10 cases of neuroendocrine neoplasms with metastasis to the scalp reported in the literature. Herein, we report an unusual case of colonic neuroendocrine carcinoma with scalp metastasis, that can be microscopically indistinguishable from the highly aggressive cutaneous neuroendocrine carcinoma, Merkel Cell Carcinoma.

Methods/Case Report

A 47-year-old female with a history of ileocecal neuroendocrine carcinoma and status post right hemicolectomy had developed liver metastasis and subsequently had an orthotopic liver transplant. PET scan later revealed multiple areas of increased activity involving the ribs, scalp and cervical lymph node that were concerning for malignancy. The scalp lesion consisted of a 7mm non-tender, mobile, violaceous, erythematous dermal nodule that was clinically concerning for cutaneous metastasis. A skin punch biopsy microscopically revealed a subcutaneous infiltrate of nests composed of neoplastic monotonous blue cells with the classic nuclear “salt and pepper” chromatin and scant eosinophilic cytoplasm. The lesional cells showed positive immunoreactivity for synaptophysin and chromogranin. With the given patient’s clinical history and presentation, the observed histological findings and immunophenotypic expression of the tumor cells supported a diagnosis of metastatic neuroendocrine carcinoma.

Results (if a Case Study enter NA)

N/A

Conclusion

Metastatic neuroendocrine carcinoma to the scalp is a rare entity and is infrequently encountered in dermatopathology. Given the location and the gross appearance of the scalp lesion, a wide differential diagnosis would include both benign and malignant tumors. In particular, Merkel Cell Carcinoma can grossly and histologically mimic metastatic colonic neuroendocrine carcinoma. Both entities would show synaptophysin and chromogranin uptake. However, metastatic tumors originating from the colon will demontrate CDX2 and SATB2 nuclear staining. We share this rare case of metastatic colonic neuroendocrine carcinoma as it is an important differential diagnosis for primary cutaneous Merkel Cell Carcinoma.
Skin Involvement by Erdheim-Chester Disease; A Case Report
Authors: Meawad H , Bamdad S , Peng S
Published: October 2021

Introduction/Objective

Erdheim-Chester Disease (ECD) is considered one of the rare forms of non-Langerhans cell histiocytosis. It is caused by infiltration of different organs with lipid-laden histiocytes with foamy cytoplasm. Clinically, it can present as an indolent localized disease or a fatal disease with multi-organ failure.

Methods/Case Report

Here we report a case of fifty year-old female with a history of Erdheim Chester disease involvement of the left parietal lobe presented to the dermatology clinic with purpuric, tender maculopapular rash on bilateral cheeks, trunk, and bilateral upper extremities. Biopsy of the lesion on central chest revealed acute and chronic superficial dermal inflammation and skin crusting. The dermis is also infiltrated by many foamy lipid-laden macrophages. These macrophages stained with CD68 and CD163 and were S-100 and CD1a negative. BRAF V600E mutation was detected. Based on the immunophenotypic characteristics, as well as the molecular testing results and the clinical history of the patient, diagnosis of cutaneous involvement by Erdheim- Chester disease was made.

Results (if a Case Study enter NA)

NA

Conclusion

In summary, despite the fact that skin involvement by Erdheim- Chester disease is rare, it is imperative to consider it in the differential diagnosis of histiocytic diseases affecting the skin and differentiate it from its histologic mimickers. Molecular testing is a helpful tool in the diagnosis of Erdheim-Chester disease. Accurate diagnosis is crucial for guiding treatment plans.
Incidence and outcomes of primary cutaneous anaplastic large cell lymphoma: a SEER population-based study
Authors: Deb P Q , Hurley H J , Bhate C , Cai D
Published: October 2021

Introduction/Objective

Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is the second most type of cutaneous lymphoma of T cell origin. Although PC-ALCL is considered clinically indolent with an excellent overall survival rate, very few studies have examined the epidemiology and survival of this disease in significant depth. Here we have used the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database to identify the cases of PC-ALCL with immunohistologic or molecular confirmation and analyzed disease-specific survival across various epidemiological factors.

Methods/Case Report

We identified patients with PC-ALCL from the SEER database from 1975 - 2017. Cases with only histological and immunohistochemical or molecular evidence of diagnosis were included in the study. Age, sex, and race-standardized incidence rates (IR) were calculated. Survival was assessed using Kaplan-Meier curves and Cox proportional hazards models.

Results (if a Case Study enter NA)

93 individuals were identified with a diagnosis of PC-ALCL. Increased age correlated significantly with the total number of cases within age groups, suggesting an associated risk. Males were significantly overrepresented in the disease population at 62%. The racial distribution of patients with PC-ALCL did not significantly differ from the racial distribution in the US. Kaplan-Meier DSS analysis was performed to assess possible influence of race, sex, age, or primary site location on the prognosis in patients with PC-ALCL. Age appears to be one of the greatest factors influencing survival, and while this trended strongly, it was not a statistically significant observation. Although males were disproportionately represented among PC-ALCL patients, sex did not affect survival. Similarly, the patient’s race had no significant effect on the length of survival. The location of the primary tumor trends towards affecting survival, and while this is quantitatively the most impressive observation, it does not reach the threshold of statistical significance.

Conclusion

We performed a comprehensive review of the clinical and epidemiological features present in PC-ALCL. We found age to be the most significant factor in the risk of development of PC-ALCL, and while our study lacks the statistical power to demonstrate it, age may also be the most significant factor in survival.
An Effective Approach for Endocrine Dynamic Function Tests Workflow and Reporting Using Cerner Millennium®
Authors: Asinas J M , Khaiwi W , Miller A , Newland P
Published: October 2021

Introduction/Objective

Endocrine dynamic function testing (DFT), also known as hormone stimulation tests, are indispensable tools in the endocrine practice. Common pitfalls of ineffective testing and misdiagnosis are due to incorrect sample recordings, delay in sample collections and disorganized or confusing result presentation. Clinical and laboratory data deserves careful attention and discrepancies must be reviewed by a clinical biochemist before releasing results for proper patient diagnosis. The main objective of this Cerner DFT project is to design and implement Cerner Millennium applications for effective management and organized result reporting of hospital-wide DFT protocols.

Methods/Case Report

The DFT Cerner workflow is uniquely designed in-house and known as a pioneer build for Cerner Millenium. The design involves the use of Cerner Discern Analytics 2.0 and clinical modules to complete such a complex build. Five DFT panels are defined as care-sets with specific hormone discrete task assays (DTA). For each care-set, an ‘order sentence’ is created to produce the order priority rules. The DFT panels can only be requested as future orders in PowerChart and activated by the medical staff upon collection of the baseline sample. On Cerner PathNet, results are pre-verified by the medical technologists then auto-filtered in the clinical Review Queue (RQ) module for final verification and addition of comments by the biochemistry consultant. A word processing template is used to collate the results and present the summary of the DFT report where standardized canned comments are added using pre-defined codes.

Results (if a Case Study enter NA)

See Conclusion Section

Conclusion

The Cerner DFT project mproves the diagnosis and treatment of patients with hormone disorders. Before, there was a danger of misdiagnosis when samples are individually requested producing separate reports with no organized presentation. Report comments from the clinical biochemist consultant also served as good diagnostic guidance. This quality initiative has definitely improved the previous and long term issues of endocrine dynamic function tests.
Parathyroid Hormone Related Peptide Elevations in Normocalcemic Adults
Authors: Freund R , Murphy V , Li D
Published: October 2021

Introduction/Objective

Elevated parathyroid hormone-related peptide (PTHrP) is a biomarker often associated with hypercalcemia of malignancy. However, elevations of PTHrP can be seen in non-malignant patients with normal calcium status, notably renal failure. We investigate whether a LC-MS/MS test that specifically measures a peptide in the middle region of PTHrP fragments is immune to false elevations of PTHrP. Furthermore, we examine if PTHrP/PTH ratio or renal status can be used to further characterize PTHrP elevations in a cohort of normocalcemic patients.

Methods/Case Report

We conducted a retrospective study on adult patients that had at least one PTHrP laboratory test (i.e., ARUP PTHrP by LC-MS/MS) within the past 10 years (01/01/2011 to 04/29/2021) at a large academic center. We further stratified this cohort by demographics and additional laboratory markers including calcium status, parathyroid hormone (PTH) (i.e., by Siemens Centaur assay (Malvern, PA)), renal status, and known malignancies.

Results (if a Case Study enter NA)

We identified a total of 941 patients (585 female and 356 male). 33% of patients (30% [70/233] female and 36% [84/236] male) with elevated PTHrP were normocalcemic (i.e., did not have an elevation in calcium, ionized calcium, or diagnosis of hypercalcemia). 95% (21/22) of normocalcemic males and 100% (17/17) of normocalcemic females with an elevated PTHrP and elevated PTH had a PTHrP/PTH ratio below the normal sex specific reference ranges of 1.07 and 1.86, respectively. A subset of normocalcemic patients with elevated PTHrP had an estimated glomerular filtration rate (eGFR) recorded. Of these patients, 100% (58/58) of females and 94% (65/59) of males had an eGFR below 90 mL/min/1.73 m2 had an eGFR less than 30 mL/min/1.73 m2. and 50% (29/58) of females and 38% (26/69) of males

Conclusion

Our study supports the hypothesis that elevated PTHrP in the setting of normal calcium may occur due to renal insufficiency.
Effect of Fasting and Postprandial Blood Samples in Results of Thyroid Function Tests Among Euthyroid People and Patients with Thyroid Problems: A Systematic Review and Meta-Analysis
Authors: Almuhaidib S A
Published: October 2021

Introduction/Objective

Thyroid disorders are considered to have a significant global health impact, affecting around 200 million people, and about 5% of all populations are diagnosed with hypothyroidism. Thyroid problems are mainly diagnosed by the laboratory’s thyroid function tests (TSH, FT4, and FT3), and currently, there is no special guideline for a preferred sample to test the thyroid functions.

Aim

To investigate whether using a fasting serum sample or postprandial serum sample could affect the results of the thyroid function tests in both euthyroid people and patients with thyroid problems.

Methods/Case Report

• A systematic search was done on PubMed, EMBASE, Google Scholar, Semantic Scholar, and manual searches with cross-referencing.

• PECOS framework was used for developing the research question.

• PRISMA guidelines used for the methodology.

• Two meta-analyses for TSH and FT4 were done based on the participant’s thyroid status, and one meta-analysis done for the FT3 for all.

• Statistical analyses were done using Revman5 software.

Results (if a Case Study enter NA)

• Ten full-text studies and three abstracts were included for the systematic review, and for meta-analysis, nine full-text studies and two abstracts.

• Based on the Cochrane rule of thumbs of the effect size interpretations, the meta-analyses result showed a statistically significant moderate effect for TSH mean differences; Mean of fasting blood sample > mean of the postprandial sample.

• TSH effect for euthyroid people based on results of 9 studies from 641 participants (MD, 0.58; Fixed, 95% CI: [0.44 to 0.73], p. <.00001).

• TSH results for all based on results of 11 studies from 921 participants (SMD, 0.46; Random, 95% CI: [0.31 to 0.61], p. <.00001).

• No statistically significant effect for FT4 and FT3 mean differences results.

• Publication bias is suggested for TSH and FT3 results due to the asymmetrical appearance, but not for FT4.

Conclusion

• In conclusion, the use of fasting blood samples would have a significantly higher TSH result value compared to the postprandial blood samples. Hence, it may help introduce a new guideline to standardize the blood sampling status for the TSH test screening and diagnosis. Alternatively, different reference ranges depending on the sampling status might be suggested, which might help promote the patients’ quality of life and reduce healthcare costs.
Frequency and factors associated with thyroid dysfunctions: An analytical cross-sectional study from a tertiary care center in Kabul, Afghanistan
Authors: Naeem M
Published: October 2021

Introduction/Objective

Endocrinopathies are a commonly occurring entity, particularly those of the thyroid gland, however there is lack of scientific literature from Afghanistan, a country with very limited health care facilities and resources. This is the first study aimed to describe the frequency of occurrence and factor associated with thyroid dysfunction in Afghan population. The aim of this study is to estimate the frequency and to identify factors associated with thyroid dysfunction among individuals coming to a tertiary care facility in Kabul, Afghanistan.

Methods/Case Report

A cross-sectional study was conducted from July to Sep 2018 at the Department of Clinical Pathology, French Medical Institute for Mothers and Children (FMIC), Kabul, Afghanistan. Blood samples were obtained, serum TSH levels were analyzed, and the patients were divided into three diagnostic categories according to their serum TSH concentrations: 1) Hypothyroidism 2) Hyperthyroidism 3) normal.

Results (if a Case Study enter NA)

A total of 127 individuals were included in the final analysis. Majority study participants (77%) were females. A large number of the participants (92%) did not have family history of thyroid dysfunction. (74%) participants in the study had normal TSH levels classified as normal thyroid function, (14%) had lower TSH levels and (12%) higher TSH levels (Table 1) classified as hyper and hypothyroid respectively.

Conclusion

The findings of the current study showed a high frequency of thyroid dysfunctions from a single center. Further large scale studies are needed to find out the prevalence and document this entity for better health outcomes in the country.
ARMC5-associated Bilateral Macronodular Adrenocortical Hyperplasia: A Novel Germline Variant Associated with Concomitant Papillary Thyroid Carcinoma and Meningioma
Authors: Strauss K , Smith S , Grover A
Published: October 2021

Introduction/Objective

Germline mutations in the tumor suppressor gene Armadillo-containing repeat protein 5 gene (ARMC5) have been very recently recognized as a cause for a familial form of bilateral macronodular adrenocortical hyperplasia (BMAH), itself a rare cause of Cushing syndrome. In patients with ARMC5 mutations, scattered case reports have also shown an association with meningiomas and cancers of the pancreas, breast, colon, and thyroid.

Methods/Case Report

We present the case of BMAH, arising in a 61-year-old female with a history of metastatic papillary thyroid carcinoma and meningioma. The patient presented with bilateral but asymmetric adrenal enlargement (right greater than left) and Cushing syndrome. Given history of thyroid cancer and meningioma, genetics referral was ordered. Counseling revealed a pedigree without a strongly evident familial pattern of hereditary endocrine neoplasia characteristic of any of the more common inherited dispositions to endocrine neoplasia. Additionally, a targeted capture-based NGS germline genetic sequencing study for variants in 12 genes associated with associated with hereditary thyroid cancer was performed and negative. However, based on recent scholarship regarding ARMC5, follow-up germline NGS and Sanger sequencing studies encompassing the entire coding sequences of ARMC5 were ordered. These identified a germline, heterozygous, novel (not in ClinVar) but likely pathogenic variant in (c.802C>T, p.Arg268*), providing a likely explanation for the patient’s BMAH. In attempt to control the patient’s Cushing symptoms, right-sided adrenalectomy was performed, revealing a 220g adrenal gland with marked multinodular hyperplasia with solid, nested, and tubular architecture.

Results (if a Case Study enter NA)

NA

Conclusion

While case reports exist describing an association between other ARMC5 mutations and BMAH with concomitant meningiomas and/or malignancies, greater study is needed in order to better characterize the phenotypic spectrum of this disease. Our experience with this case not only reports a novel, apparently pathogenic mutation, but it documents its association with BMAH and, additionally, papillary thyroid carcinoma and meningioma.
Neuroendocrine tumors and Survival- a meta-analysis
Authors: Khayyat A , Asad M , Aslam A , Rabbani R , Fabara S , Chandramohan S , Unachukwu N , Nasyrlaeva B , Chowdary S , Hammoud G , Jaiswal R
Published: October 2021

Introduction/Objective

Neuroendocrine tumors (NET) are a rare group of epithelial neoplasm present in gastrointestinal tract (GI) (67.5%), bronchopulmonary tree (25.3-30%) and in 15% cases primary sites cannot be identified. Although endoscopic screening, improvement in pathological techniques and early detection have shown improvement in NET survival rates, the prognosis is very poor. In this study we aimed to evaluate the effect of Gastrointestinal pancreatic NETs (GEP NETs) grade on overall survival.

Methods/Case Report

We searched observational studies describing the overall survival or prognostic factors of primary GEP NETs from May 2011 -May 2021 following PRISMA guidelines. Studies describing the effect of primary grade 3 GEP NETs on overall survival were included. Meta-analysis was performed and pooled hazard ratio and their 95% confidence interval (95%CI) were obtained. The forest plots were created using random effects models and sensitivity analysis was performed to account for the heterogeneity.

Results (if a Case Study enter NA)

Seven studies with 7692 confirmed patients were included. In our meta-analysis grade 3 GEP NET were associated with higher odds of poor survival (pooled HR: 2.73; 95% CI: 1.36–5.47; p = 0.005), with 92% heterogeneity between studies (p < 0.0001). To account for heterogeneity, sensitivity analysis was performed by removing two outlying studies (Fathi et al. and Foubert et al.) on funnel plots. The results after sensitivity analysis did not change and still showed significant association of grade 3 with poor survival (pooled HR: 4.53; 95% CI: 3.54–5.78; p < 0.00001), with no heterogeneity between studies (p = 0.72; I2 = 0%).

Conclusion

Our meta-analysis found that grade 3 GEP NETs is associated with poor survival and additional future studies are needed to identify other risk factors associated with poor survival in GEP NETs to improve the mortality.
Submucosal Lipoma at the lead point of Small bowel Intussusception in an Adult
Authors: Kiran F , Asuzu I M , Noreen S
Published: October 2021

Introduction/Objective

Morbidity and mortality among adult patients presenting with acute abdominal pain are high, and these patients often require hospitalization with prompt surgical consultation Important differentials include small bowel obstruction from previous surgeries and hernias, acute mesenteric ischemia, and ruptured abdominal aortic aneurysm. Intussusception in adults is rare accounting for about 1% - 5% of small bowel obstructions and thus requiring a high index of suspicion for early detection. In most cases, the lead point is a benign mass, commonly a lipoma, but histopathologic examination of the resected segment is required to rule out malignancy.

Methods/Case Report

We present a case of a 50-year old male with a medical history of psoriasis and hypertension who was admitted on account of a 1-day history of sudden onset persistent abdominal pain with associated nausea non-bilious emesis. Physical examination reveals no fever and soft non-distended abdomen with diffuse tenderness. CT scan demonstrated long segment small bowel-small bowel intussusception with markedly edematous and dilated bowel, compatible with obstruction. The lead-point was suspected to be a 3.9cm lipoma. Segmental resection and primary re-anastomosis were performed. Gross examination revealed a 13cm segment of bowel telescoping into a distal segment with a lead-point demonstrating mucosal congestion and submucosal thickening corresponding to a well-circumscribed 3.5cm tan yellow soft lobulated mass with yellow cut surface. Histopathology was consistent with lipoma. The patient made an uneventful postoperative recovery.

Results (if a Case Study enter NA)

N/A

Conclusion

Intussusception should be kept in the differential diagnosis of adults presenting with sudden onset abdominal pain and pathologic examination of the resected segment is necessary to rule out malignancy.