Three shades of an unusual mediastinal tumour.

Thoracic SMARCA4-deficient undifferentiated tumour (SMARCA4-UT) is an unusual and aggressive tumour. While there are approximately 100 cases of this tumour reported in the literature, there are very few detailed descriptions of its cytomorphologic characteristics, and only rare cases in which primary diagnosis was made on cytologic material. Herein we present a case with a detailed description of the appearance on three specimen types: transbronchial needle aspiration (TBNA) cytology, transbronchial needle biopsy (TBNB) and effusion cytology. Thoracic SMARCA4-UT is an important diagnosis to clinch in modern pathology because of its prognostic and therapeutic implications. We discuss an integrated approach to clinching the diagnosis with reference to clinical, radiographic, morphologic and immunohistochemical features. We also discuss possible differential diagnoses, and how they can be excluded. Cytologic and/or small biopsy diagnosis is valuable in these cases as these tumours are typically not amenable to surgical resection. With the correct diagnosis, the patient may instead be a candidate for immune checkpoint inhibitors or experimental therapy targeting SWI/SNF deficiency.

A single tertiary institution review of the international system for serous fluid cytopathology and the impact of cell block and ancillary studies on its performance.

INTRODUCTION: We sought to assess the utility of the International System for Serous Fluid Cytopathology (TIS) in the context of our department's routine practice. MATERIALS AND METHODS: We examined 1028 archived effusion cytology (pleural, peritoneal, and pericardial) cases from 2018 to 2019, and re-classified them along the international system into the following diagnostic categories: nondiagnostic (ND), negative for malignancy (NFM), atypia cells of undetermined significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). RESULTS: The full distribution of the cases examined was as follows: ND 2.0%; NFM 66.1%; AUS 6.0%; SFM 4.7%; MAL 21.2%. Overall risk of malignancy for each category was calculated as: ND 30.0%; NFM 18.0%; AUS 61.9%; SFM 100%; MAL 94.4%. The overall performance attributes of TIS were as follows: sensitivity 57.1%; specificity 98.3%; positive predictive value 94.4%; negative predictive value 82.0%; diagnostic accuracy 84.5%. CONCLUSIONS: The new classification was simple and intuitive to use and our results appear to fall within the expected ranges of the new guidelines, with risk of malignancy and accuracy comparable to similar studies. The availability of a cell block allowed for refinement of the diagnosis in a majority of cases with equivocal cytology, though this was dependent on the cell yield.

Artificial intelligence defines protein-based classification of thyroid nodules.

Determination of malignancy in thyroid nodules remains a major diagnostic challenge. Here we report the feasibility and clinical utility of developing an AI-defined protein-based biomarker panel for diagnostic classification of thyroid nodules: based initially on formalin-fixed paraffin-embedded (FFPE), and further refined for fine-needle aspiration (FNA) tissue specimens of minute amounts which pose technical challenges for other methods. We first developed a neural network model of 19 protein biomarkers based on the proteomes of 1724 FFPE thyroid tissue samples from a retrospective cohort. This classifier achieved over 91% accuracy in the discovery set for classifying malignant thyroid nodules. The classifier was externally validated by blinded analyses in a retrospective cohort of 288 nodules (89% accuracy; FFPE) and a prospective cohort of 294 FNA biopsies (85% accuracy) from twelve independent clinical centers. This study shows that integrating high-throughput proteomics and AI technology in multi-center retrospective and prospective clinical cohorts facilitates precise disease diagnosis which is otherwise difficult to achieve by other methods.

DPHL: A DIA Pan-human Protein Mass Spectrometry Library for Robust Biomarker Discovery.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Right Parietal Skull Xanthoma Characterized as a Metastatic Deposit.

BACKGROUND: Xanthomas are benign lipomatous deposits that can be found systemically in various tissues including bones. Their presence in the skull remains a rare entity. Despite their benign characteristics, imaging modalities are often unable to distinguish them from malignant lesions. This leads to a diagnostic dilemma in patients with underlying malignancy. This case report highlights such a case where clinical history of prostate cancer and image findings were concordant with that of metastatic deposit in the parietal skull region. CASE DESCRIPTION: This 65-year-old gentleman was diagnosed with prostatic adenocarcinoma. During systemic workup for his tumor, he was found to have a right parietal skull lesion. Magnetic resonance imaging of the brain, as well as a bone scan, were consistent with that of a metastatic deposit. As treatment would be drastically affected by the diagnosis, an excision biopsy was performed. The histology was consistent with that of a bone xanthoma. CONCLUSIONS: Xanthomas are benign lesions that can be seen deposited in appendicular and axial skeleton. Skull lesions are rare with most case descriptions focusing on their presence in the frontoorbital regions and mandible and temporal bone. They usually have a benign course but may present with symptoms due to localized mass effect. Surgical intervention and histologic diagnosis may still be required in these lesions due to their lack of imaging characteristics that confirm their diagnosis through noninvasive methods.

Cytologic features of tubular adenoma of ampulla causing distal common bile duct stricture: A case report and review of the literature.

Adenomas of the ampulla of Vater are distinctly rare, representing <10% of periampullary neoplasms. Very few reports of the cytologic features of ampullary adenomas are present in literature, particularly in bile duct brushing samples. A case report and review of the literature is presented. The typical cytologic features of ampullary adenomas on cytologic preparations include tall, thin columnar cells with mildly hyperchromatic elongated nuclei and nuclear pseudostratification, in a relatively clean background. The key differential diagnostic entities include invasive adenocarcinoma, thermal artifact, and reactive atypia.

Heterotopic pancreas in the omphalomesenteric duct remnant in a 9-month-old girl: a case report and literature review.

BACKGROUND: Heterotopic pancreas most commonly occurs in the upper gastrointestinal tract of adults, usually as an incidental finding. It seldom occurs at the umbilicus, and even rarely in the pediatric age group. CASE PRESENTATION: Here we present a case of heterotopic pancreatic tissue in the omphalomesenteric duct remnant of a 9-month-old baby girl. She presented with redness at the base of the umbilicus associated with occasional mild wetness. A urachal fistula was suspected by ultrasound. Histology from subsequent resection revealed fibrous tissue with heterotopic pancreatic tissue and accompanying small bowel mucosa. The patient's umbilical redness resolved after the surgery. CONCLUSIONS: Upon literature search, we found only 17 other cases of heterotopic pancreas reported in the umbilicus. They described a high male to female ratio, frequent association with omphalomesenteric duct remnant and presentation of umbilical discharge. The Heinrich system is frequently used to classify heterotopic pancreas into 3 types, based on the presence of acini, islets and ducts. Several mechanisms have been proposed on the pathogenesis of heterotopic pancreas, including misplacement, metaplasia and totipotent cell theories. Heterotopic pancreas can manifest clinically with diseases of the pancreas, including malignant transformation, reported as high as 12.7% in a series. Awareness of this finding in the biopsy aids the suitable treatment decisions for the patient.

Synchronous invasive ductal carcinoma and intravascular large B-cell lymphoma of the breast: a case report and review of the literature.

Primary breast lymphomas (PBLs) represent less than 1% of all breast malignancies. Intravascular large B-cell lymphoma (ILBCL) is a rare, aggressive form of extranodal lymphoma. Breast involvement has only been described in the literature once previously. ILBCL is characterized by the proliferation of tumour cells within the lumen of small vessels of involved organs, resulting in their eventual occlusion. Clinical features are often vague, diagnosis is difficult and delayed, and prognosis is usually poor. We report the first ever case of synchronous ILBCL and invasive ductal carcinoma (IDC) of the breast in a patient presenting with pyrexia of unknown origin and altered mental status who underwent modified radical mastectomy and subsequent chemotherapy, and review the literature regarding intravascular large B-cell lymphoma, PBLs and synchronous carcinomas and lymphomas of the breast.

A rare case of localised AA-type amyloidosis of the ureter with spheroids of amyloid.

We present a case of localised AA-type amyloidosis of the ureter with spheroids of amyloid. Localised AA-type amyloidosis of the urogenital tract is uncommon and extremely rare as a cause of ureteric obstruction, with only two such cases described in the literature to date. Most previously described cases at this site are related to primary AL-type amyloidosis. Another interesting finding in this case is the presence of spheroids of amyloid, which to the best of our knowledge, has not been previously reported at this site, and is also unusual at other sites.

Deep anterior lamellar keratoplasty to treat microsporidial stromal keratitis.

PURPOSE: To describe deep anterior lamellar keratoplasty (DALK) as a surgical option to treat a case of severe microsporidial stromal keratitis in an immunocompetent patient. MATERIALS AND METHODS: This study is a descriptive case report. A 42 year-old Pakistani woman had an 8-year history of symptoms in the left eye. She had been previously provisionally diagnosed as suspected herpes simplex keratitis or Thygeson keratitis. At presentation, her best-corrected visual acuity was 20/20 OD and 20/200 OS. Examination of the left cornea revealed irregular, central, deep stromal opacification with keratitic precipitates and occasional cells in the anterior chamber. Investigations for mycobacteria, syphilis, and a tetraplex test were normal; all other hematological/biochemistry/virology investigations were normal-she was not found to be immunocompromised. RESULTS: A corneal biopsy confirmed microsporidial infiltration of the stroma. After intensive medical treatment with topical fumagillin and oral albendazole without resolution, DALK was performed with total stromal replacement using the big-bubble technique. One year postoperatively, the graft remained clear with no evidence of recurrence and best-corrected visual acuity was 20/40 OS. CONCLUSIONS: Microsporidial stromal keratitis is rare. Conventional surgical treatment for such a condition has been penetrating keratoplasty. DALK may be considered an option for visual rehabilitation in these cases.