bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calretinin-Positive Mucosal Innervation (C-mi) as a Potential Biomarker to Predict Fibrosis in Crohn’s Disease (CD): A Pilot Study
Authors: Arslan M , Li H , Lee H , Mikula M , Ahn S 
Published: October 2020

Abstract

Introduction/Objective
There is no reliable biomarker to predict the degree of fibrosis in CD. Quantification of C-mi has been used as a surrogate for enteric neural structures in Hirschsprung disease. The quantity of C-mi at the proximal margin may correlate with the degree of fibrosis in resected CD.

Methods
Ileocolonic resection cases for 20 CD and 3 trauma (control) were retrieved. Cases with severe mucosal inflammation at the margins were excluded. The proximal and distal margin sections were subjected to calretinin immunohistochemistry. Random mucosal images were captured from scanned slides (x200, JPEG), submucosa was edited out, and C-mi was calculated by image processing and analysis. rC-mi was defined as the mean C-mi of proximal margin normalized by that of distal margin. Cases with rC-mi less than the mean rC-mi + 2 SD of the controls were excluded. The maximum thicknesses of submucosa and muscularis propria were measured at the most stenotic site, microscopically. Pearson’s correlation test and Student’s t-test were performed to correlate the parameters and compare the means, respectively.

Results
A total of 216 images were captured (mean 9.3 images per case; range 7 to 10). The mean rC-mi of CD (1.26) was greater than the controls (mean 0.43) (p&lt;0.05). The mean rC-mi + 2 SD of the control group was 0.91, thus 2 CD cases were excluded from final analysis. The rC-mi of CD showed an inverse relationship with maximum submucosal thickness (mean 3.4 mm, range 0.2 to 5.9) at the site of stenosis (r=-0.47; p&lt;0.05), but not with muscularis propria.

Conclusion
The rC-mi of CD was inversely correlated with submucosal fibrosis. Altered stromal integrity, impaired intercellular signaling, progressive reduction and loss of telocytes induced by submucosal fibrosis may reduce the regenerative capacity of enteric neural structures in CD. Therefore, a decreasing trend in rC-mi may predict fibrosis progression in CD.
Intraductal Papillary Adenocarcinoma Of The Bile Duct With Associated Invasive Neuroendocrine Component: Case Report
Authors: Alhussain A , Abraham A , Grunes D , Subramony C 
Published: October 2020

Abstract

Casestudy
Intraductal papillary neoplasm of the bile duct (IPNB) is a variant of bile duct carcinoma that is characterized by intraductal growth and better outcomes compared with common cholangiocarcinoma. IPNBs are mainly found in patients from Far Eastern countries, where hepatolithiasis and clonorchiasis are endemic.
Approximately 40%-80% of IPNBs are associated with invasive carcinoma. The invasive carcinomas are most often tubular or mucinous type. Invasive neuroendocrine component has not been previously described.
We present a case of 69 year-old African American male who presented with worsening abdominal pain and jaundice over few months. Computed tomography showed 4 cm mass near the porta hepatis with massive ductal dilatation. A fine needle aspiration of the mass was performed and a diagnosis of adenocarcinoma was made. Subsequently, the patient underwent Right Trisegmentectomy.

Conclusion
Histologic sections revealed intraductal papillary neoplasm in the bile duct lumina. The papillae were lined by columnar epithelial cells with delicate fibrovascular cores. The tumor cell nuclei were slightly elongated, hyperchromatic and basally located without significant multilayering. The cytoplasm was eosinophilic with occasional intestinal differentiation. Frank invasion of the stalk and underlying periductular tissues was identified. Interestingly; the invasive component had different cytological features than the intraductal component, it was composed of small to medium sized cells with granular cytoplasm. The nuclei were uniform and round with “salt and pepper” chromatin. The invasive component stained positively for the neuroendocrine markers (Synaptophysin, Chromogranin and CD56), whereas the intraductal component stained positively for CK7, CK20 and CDX2 and negative for neuroendocrine markers.
Three years later, a recurrent tumor was found in the left lobe on imaging. Biopsy of the lesion showed metastatic neuroendocrine carcinoma. The intraductal papillary neoplasm with invasive neuroendocrine component is very unusual tumor, we think more studies are warranted to best evaluate the treatment options and the prognosis of such neoplasms.
Identification Of Strn-Ntrk2 Rearrangement In A High Grade Sarcoma, With Good Clinical Response To Firstline Larotrectinib Therapy
Authors: Lin R , Wang Z , Jiang W , Basu-Mallick A 
Published: October 2020

Abstract

Casestudy
Gene fusions involving tropomyosin receptor kinase genes, NTRK (NTRK1-3), are important in tumorigenesis. Larotrectinib, a selective NTRK inhibitor, is recently approved to treat NTRK fusion positive solid tumors. We herein report a case of soft tissue sarcoma harboring two STRN-NTRK2 gene fusions, with good clinical response to firstline larotrectinib treatment.

Results
A 35 year-old female presented with pain in the right gluteal region, and a large solid mass without overlying erythema, edema and induration was identified. Initial MRI study showed a heterogenous, vascular and partially necrotic mass (16.5 x 12.9 x 10.4 cm) centered in the right gluteus medius and maximus muscles. A core biopsy of the mass showed a cellular mesenchymal neoplasm with round/ovoid cells, high mitosis (21 per 10 HPFs) and focal staghorn type vessels, reminiscent of solitary fibrous tumor. However, STAT6 immunostaining was negative.
Additional immunostains show no specific lineage. Our in-house NGS fusion panel showed two in-frame STRNNTRK2 fusions, containing the same 5’ partner sequence (exon 1-3) of STRN, with the 3’ fusion partner starting from either the exon 15 or the exon 16 of NTRK2. Due to the large size and location of the tumor, larotrectinib was initiated as firstline therapy. The patient noticed a quick amelioration of tumor related pain, and a significant shrinkage of the size of tumor following the initial 7-day treatment. On post-treatment day 52, MRI showed the tumor significantly decreased in size to 7.7 x 7.4 x 6.6 cm with satisfactory symptomatic relief.

Conclusion
NTRK2 fusions are relatively rare when compared with NTRK1 and NTRK3, especially in sarcoma. Of note, the only other report in the literature of NRTK2 fusion- positive sarcoma also showed SFT-like morphology, and the patient responded well to larotrectinib as second line therapy.
Tactile Corpuscle-like Bodies in Rectal Mucosa - A Mysterious Misleading Lesion
Authors: Anderson S A , Dal Zotto V 
Published: October 2020

Abstract

Introduction/Objective
Tactile corpuscle-like bodies (TCLB) are specialized mechanoreceptors derived from Schwannian structures, resembling Wagner-Meissner corpuscles which are often found in the skin and within schwannomas, neurofibromas, and melanocytic nevi. However, their presence in gastrointestinal mucosa is a rare phenomenon. To our knowledge, only 27 cases have been reported in the English literature.

Methods
We present two cases showing this rare entity in rectal mucosa. The first case is in a 34-year-old female was a past medical history significant for Ehlers-Danlos syndrome. The second case was submitted in consultation, of a 64-year-old male. In both cases, rectal polyps were identified on endoscopy.

Results
Histologically, clusters of unencapsulated, lamellated spindle cells in the lamina propria were identified. Immunoperoxidase stains using antibodies against CD68 and S100 protein were performed on both specimens. Additionally, on the first case synaptophysin was also performed. The laminated clusters were strongly positive for S100 and negative for CD68. The first case showed focally positive synatophysin. Although the etiology of TCLBs is still unclear, they are considered to be benign, incidental neural proliferations. The histological differential diagnosis includes: schwann cell hamartomas, neurofibromas, ganglioneuromas, mucosal neuromas, nodular amyloid deposition, or granulomas. However, those in question can be differentiated with the use of S100 protein and histiocytic markers.

Conclusion
Awareness of TCLBs is important. Although they are benign neural proliferations, it is important to differentiate from histologic mimics often associated with inherited syndromes.
Identification Of Liver Fluke Eggs In Bile Duct Brush Cytology In An 82 Year Old Man With A Hepatic Mass: Report Of A Case
Authors: Chen F , Aguero-Rosenfeld M , Simsir A , Brandler T C 
Published: October 2020

Abstract

Introduction/Objective
Clonorchis sinensis infects the liver, gallbladder, and bile ducts in humans. It is acquired via consumption of raw/undercooked fish, crabs, or crayfish in endemic areas. Though majority are asymptomatic, long lasting infections may cause severe disease. Without treatment, human infections may persist for the parasite lifespan (25–30 years). Diagnosis in cytology is challenging with a potentially acellular sample with miniscule eggs that can be overlooked as an artifact. Here we reported a rare case of liver fluke eggs diagnosed in bile duct brush cytology.

Methods
An 82 year old man who emigrated from China 20 years prior presented to the hospital with worsening jaundice for 2 weeks. Abdominal CT revealed a 4.8 x 2.9 cm central right hepatic lobe mass extending to the hilum, obstructing the bile ducts, resulting in severe intrahepatic ductal dilatation and stricture and focal occlusion of the right anterior portal vein. His CBC revealed eosinophilia. Bile duct brushing was submitted for cytology.

Results
ThinPrep and cell block showed oval-shaped parasite eggs measuring 10-24 µm. There was no other cellular matter. Eggs had a convex operculum resting on “shoulders” at the smaller end of the egg. At the opposite (abopercular) end, a small knob or hook-like protrusion was often visible. Wet mounts revealed visible miracidium inside the eggs. These findings were compatible with liver fluke eggs.

Conclusion
Cytologic microbiologic features of fluke eggs confirmed the findings. The most important features are the shape and size of the eggs; The seated operculum with its prominent “shoulders”, a small knob at the abopercular end, which can distinguish them from acellular artifact or a human cell. The cytologic and microbiologic features combined with the travel history and clinical presentation can aid in achieving the diagnosis.
Single Institutional Experience on Cutaneous Manifestation of Adult T-cell Leukemia/Lymphoma - Potential Diagnostic Pitfall
Authors: Bridgelall S , Michalski J , Zhang X , Sokol L , Dong N , Zhang L 
Published: October 2020

Abstract

Introduction/Objective
Adult T-cell Leukemia/Lymphoma (ATLL) is an aggressive peripheral T-cell neoplasm caused by the human T-cell lymphotropic virus-1 (HTLV1). Approximately half of the patients diagnosed with ATLL have heterogeneous cutaneous manifestations and 1/3 of those patients have skin changes e.g. rashes, papules, and nodules at initial presentation. There is clinical and morphologic overlap between ATLL and other cutaneous T-cell neoplasms such as Cutaneous T-Cell Lymphoma/mycosis fungoides (CTCL/MF) which could pose a potential diagnostic challenge.

Methods
A retrospective study was conducted using PathNet system to search for HTLV1 positive ATLL patients. Clinicopathologic features of the patients with cutaneous involvement were analyzed.

Results
Total 31 patients with ATLL were identified. Nine patients (29%, median 54.5 years, range 47-67 years, male: female ratio 2:7) showed skin manifestations, and the cutaneous involvement with ATLL was confirmed by skin biopsy. Five (55.5%, 5/9) cases were initially misdiagnosed as CTCL/MF. Among the 5 patients, 2 presented with skin rash or diffuse erythematous patch/plaque before developing generalized lymphadenopathy or overt circulating atypical lymphocytosis; 2 developed severe pruritic rash with erythematous skin changes resembling Sezary syndrome; and 1 patient had folliculotrophic MF diagnosed 12 years before. Notably, atypical lymphocytosis (0.46- 41.19/µL) occurred in 3 of the 4 remaining cases. In addition, eight of the 9 patients displayed a variable level of CD3+/CD4+/ CD25strong+ abnormal T-cells on flow cytometry. A low-level bone marrow involvement (2-10%) was found in 8 of 9 cases. Elevated calcium levels were identified in 3 of 9 cases (33%). There were 7 of 8 patients (87.5%) who developed generalized lymphadenopathy when diagnosis of ATLL was rendered.

Conclusion
In patients with cutaneous manifestations, features including hypercalcemia, atypical lymphocytosis, lymphadenopathy, CD3/CD4/strong CD25 coexpression, and bone marrow involvement should prompt a test for HTLV1. Early diagnosis of ATLL can initiate proper treatment and improve patient clinical outcomes.
An Unusual Case of Basal Cell Carcinoma with Myoepithelial Differentiation
Authors: Myers D , Smith N 
Published: October 2020

Abstract

Introduction/Objective
Basal cell carcinoma (BCC) is a commonly encountered dermatologic entity by general surgical pathologists and dermatopatholgists alike and usually does not pose a diagnostic dilemma. However, BCC can take on a variety of histopathologic morphologies, sometimes mimicking more malignant entities. We present an unusual case of BCC with a rare morphology.

Methods
A 56-year-old male with history of non-melanoma skin cancer presented to his dermatologist with a 5mm pink, pearly, papule on his left forearm. A biopsy was performed, and histology and immunohistochemistry was utilized to evaluate and characterize the neoplasm.

Results
H&E stained histopathologic sections demonstrated an unusual epithelioid neoplasm with infiltrative growth, peripheral palisading of atypical basaloid cells, and areas of prominent rhabdoid/plasmacytoid cytology reminiscent of myoepithelial cells. The neoplasm was diffusely positive for Ber-Ep4 while SMA highlighted the areas with rhabdoid/plasmacytoid appearance. Mart-1 and SOX-10 were positive in only a few bland intralesional melanocytes.

Conclusion
The histological appearance was concerning for melanoma with rhabdoid morphology or an unusual variant of basal cell carcinoma. Positive Ber-Ep4 staining supported the histological impression of an unusual basal cell carcinoma variant while staining for SMA supported the impression of myoepithelial differentiation. Myoepithelial differentiation is extremely rare in BCC with only 16 prior cases described in the literature. To our knowledge, this is the first reported case of BCC with myoepithelial differentiation presenting outside the face. Consequently, this is an important diagnostic differential to consider when evaluating epithelial neoplasms with rhabdoid or plasmacytoid morphology.
Primary Conjunctival Kaposi Sarcoma; A Rare And Unheard Entity
Authors: Hussain F , Laharwani H , Sonani H , Adams K 
Published: October 2020

Abstract

Introduction/Objective
Kaposi’s sarcoma (KS) is the most common malignant vascular tumor in human immunodeficiency virus (HIV) patients caused by human herpesvirus 8. It can affect the vascular endothelium of any part of the body however ocular KS as an initial manifestation has been reported only in 3 cases so far. It affects the vascular endothelium of the lacrimal gland, eyelids, orbit, palpebral and bulbar conjunctiva. It presents as a violaceous fleshy nodular mass.

Methods
A 23-year-old male with a past medical history of HIV presented with bilateral eye erythema and significant upper and lower lid edema. The patient was initially admitted for facial swelling which led to a conjunctival biopsy and a diagnosis of KS was made and doxorubicin along with chemotherapy was started. Four months later after the initiation of chemotherapy, the patient experienced worsening of facial swelling, and an area on the left side of his face got very firm. His physical examination was positive for a fever, drooling, facial swelling with trouble swallowing, and change of voice along with shortness of breath.

Results
CT of the orbit revealed symmetric enhancement swelling of the preseptal periorbital soft tissues which was thought to be nonspecific and a differential diagnosis included lymphedema, acute sinusitis, and orbital cellulitis was considered. A chest x-ray revealed bilateral pleural effusions and CT head revealed diffuse scalp and facial cutaneous and subcutaneous edema. Lab findings were significant for a low CD4: CD8 ratio. Cytological examination of the pleural fluid revealed predominantly blood, reactive mesothelial cells, macrophages, neutrophils, and lymphocytes, and appropriately controlled immunostain was positive for ERG and HHV8 with a possibility that Kaposi’s sarcoma cannot be completely excluded. Unfortunately, the patient passed away during the same time of pleural fluid analysis.
Autopsy findings revealed multiple metastatic foci in the mediastinal soft tissue, within the right land left lung, scalp soft tissue, retroperitoneal soft tissue, and hilar lymph node which were positive for CD34, CD31, and HHV8 and consistent with metastatic KS.

Conclusion
Thus, it is important to keep in mind that isolated conjunctival KP with later on systemic metastasis is rare with conjunctiva being an unusual site for the initial presentation, and a possibility of primary conjunctival KS should be considered in HIV positive patients.
Diagnostic Approach To Oligomonocytic Chronic Myelomonocytic Leukemia
Authors: Muldoon J , Czader M 
Published: October 2020

Abstract
Casestudy: Pathologic diagnosis of chronic myelomonocytic leukemia (CMML) is typically straightforward with the majority of patients presenting with persistent monocytosis (&gt;1x109/L, &gt;=10%) and bone marrow dysplasia. The diagnosis may be challenging in patients with unusual features such as lack pf peripheral blood monocytosis and non-diagnostic bone marrow morphology. In this abstract, we present a 67-year-old female with a 5-year history of anemia of unclear etiology. At the time of initial presentation, the laboratory work-up of normocytic anemia was non- contributory, the bone marrow was reported as normocellular with maturing trilineage hematopoiesis and no significant dysplasia. Over the course of the disease, the peripheral blood monocyte count fluctuated from 11% to 18% with absolute monocyte count ranging from 0.4 to 0.7x109/L. The most recent bone marrow was markedly hypercellular with increased trilineage hematopoiesis with left shift, dysgranulopoiesis and dysmegakaryopoiesis. Blasts (including promonocytes) constituted 10% of the differential count and were immunophenotypically abnormal with uniform expression of CD117, dim to negative CD13, and partial CD15. Monocytes were elevated at 12% and were strongly positive for CD64 and partially for CD14. They were negative for CD16 consistent with classical monocytes, and showed partial loss of CD13. The karyotype was normal. Molecular testing revealed TET2, RELN and SRSF2 mutations at high allelic frequencies. This case illustrates a value of flow cytometric immunophenotyping and molecular genetic studies in diagnosing challenging cases of CMML. While the patient’s absolute monocyte count remained below the diagnostic threshold of 1x109/L throughout the course of the disease, peripheral blood and bone marrow monocytes showed skewed classical immunophenotype, immunophenotypic abnormalities of myeloid series and high allelic frequency mutations. These findings should raise a differential diagnosis of oligomonocytic CMML, even when morphologic abnormalities and monocyte count threshold are not diagnostic.
Simplification of Clinical Flow Cytometry by Adoption of Premixed Antibody Panels
Authors: Polski J M 
Published: October 2020

Abstract

Introduction/Objective
Multiparameter flow cytometry (MFC) is the standard of care for the diagnosis and monitoring of hematopoietic and lymphoid neoplasms. While MFC is a mature technology, new innovations are brought to the market. Such an innovation is the ClearLLab10C, FDA-cleared, 4-tube, 10-color, dry, premixed antibody panels (Beckman Coulter Diagnostics, Brea, California). Our laboratory decided to implement this new reagent system combined with 10-color clinical flow cytometer, Navios EX from the same vendor. This paper describes the clinical validation results for leukemia/lymphoma (LL) evaluation as well as logistical and labor savings in the laboratory.

Methods
Thirty specimens submitted for LL evaluations were tested by our existing 5-color flow cytometer with custom antibody combinations as well as by the Navios EX instrument with the ClearLLab10C product supplemented by additional antibody combinations for intracellular analysis. The validation cases included normal and abnormal cases, representing bone marrows, blood, lymph nodes, and a few other specimens.

Results
There was a complete agreement in the qualitative results.
The new simplified premixed reagents allow for noticeable simplification of inventory and saving in labor. The existing LL antibody cocktails required stocking 41 antibodies. The new platform requires only 4 LL reagents for surface immunophenotyping and we elected to stock additional 8 antibodies for optional intracellular evaluation. The amount of manual pipetting is greatly reduced. One additional advantage of utilizing the new ClearLLab10C is the available electronic and book publication from the vendor illustrating typical results for 24 normal and abnormal specimens analyzed using ClearLLab10C. This resource together with a user-friendly analysis software Kaluza C greatly facilitate interpretation of 10-color results by pathologists, medical technologists, and especially by the pathologists in training.

Conclusion
ClearLLab10C product is a cost-effective and user-friendly solution for laboratories seeking a streamlined MFC and a great reduction of inventory and labor.