Fine Needle Aspiration Cytology of the Breast: The Nonmalignant Categories

Currently, accurate diagnosis of breast lesions depends on a triple assessment approach comprising clinical, imaging and pathologic examinations. Fine needle aspiration cytology (FNAC) is widely adopted for the pathologic assessment because of its accurracy and ease of use. While much has been written about the atypical and maliganant categories of FNAC diagnosis, little covers the non-malignanat category which represents a sheer number in all FNAC cases. Moreover, any false-negative diagnosis of the non-malignant cases may lead to missed diagnosis of cancer. This paper aims to discuss the issues of smear adequacy, the cytologic features of benign breast lesions and the dilemma of a false-negative aspirate. Much has been suggested about the smear adequacy criterion, including quantifying epithelial clusters, whereas others advocate basing adequacy on qualitative quantum of using noncellular features of FNAC. Various benign lesions could be easily diagnosed at FNAC; however, they have cytologic features overlapped with malignant lesions. False negativity of FNAC does occur; this could be caused by either “true” false-negative cases attributed to suboptimal sampling technique, poor localization of the mass or nonpalpable lesions or “false” false-negative cases due to interpretational errors. Though false-positive cases are less commonly found, they will also be discussed briefly

A unique case of spontaneous regression of metastatic papillary renal cell carcinoma: a case report

Spontaneous regression of cancer is a rare, but well documented, phenomenon. We present a unique case of an 82 year old Chinese male who experienced spontaneous regression of histologically-verified metastatic type II papillary renal cell carcinoma in the absence of intervening systemic therapy or surgery. This is the first reported case of spontaneous regression of papillary renal cell carcinoma. The mechanism of spontaneous regression remains unknown, and represents a challenge for existing oncology paradigms

A Rare Case of Rectal Metastasis from Sarcomatoid Variant of Urothelial Carcinoma: A Case Report

Introduction: Urothelial carcinoma of the bladder with sarcomatoid differentiation is known to display aggressive biological behaviour. To our knowledge, this is the first reported case of isolated rectal metastasis from sarcomatoid urothelial carcinoma of the bladder following curative surgery.Presentation of Case: A 72-year-old male presented with tenesmus 6 months after radical cystoprostatectomy, lymph node dissection and ileal conduit formation for pathological T1N0M0 bladder carcinoma.Digital rectal examination revealed thickening of the distal rectum with no bleeding. Computerised tomography demonstrated thickening in the rectal mucosa and submucosa with intact perirectal fat. Rectal biopsy performed via colonoscopy confirmed metastases of urothelial carcinoma origin. The patient was treated with palliative radiation.Conclusion: This case report illustrates an unusual location of urothelial carcinoma metastasis. A high clinical suspicion in patients with this aggressive variant of cancer is required

A Preliminary Investigation into Search and Matching for Tumour Discrimination in WHO Breast Taxonomy Using Deep Networks

Breast cancer is one of the most common cancers affecting women worldwide. They include a group of malignant neoplasms with a variety of biological, clinical, and histopathological characteristics. There are more than 35 different histological forms of breast lesions that can be classified and diagnosed histologically according to cell morphology, growth, and architecture patterns. Recently, deep learning, in the field of artificial intelligence, has drawn a lot of attention for the computerized representation of medical images. Searchable digital atlases can provide pathologists with patch matching tools allowing them to search among evidently diagnosed and treated archival cases, a technology that may be regarded as computational second opinion. In this study, we indexed and analyzed the WHO breast taxonomy (Classification of Tumours 5th Ed.) spanning 35 tumour types. We visualized all tumour types using deep features extracted from a state-of-the-art deep learning model, pre-trained on millions of diagnostic histopathology images from the TCGA repository. Furthermore, we test the concept of a digital "atlas" as a reference for search and matching with rare test cases. The patch similarity search within the WHO breast taxonomy data reached over 88% accuracy when validating through "majority vote" and more than 91% accuracy when validating using top-n tumour types. These results show for the first time that complex relationships among common and rare breast lesions can be investigated using an indexed digital archive

Over-expression of the mitogen-activated protein kinase (MAPK) kinase (MEK)-MAPK in hepatocellular carcinoma: Its role in tumor progression and apoptosis

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies in South East Asia. Although activation of the MEK-MAPK is often associated with cellular growth, the role of MEK-MAPK in growth and survival of hepatocarcinoma cells has not been established. METHODS: Immuno-histochemistry was used to localize phosphorylated MAPK and MEK1/2 in the tissues. 3-(4,5-Dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay and ELISA were used to determine cell viability and cell proliferation. Deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was used to detect apoptotic cells. Western blots analysis was performed to determine the levels of proteins involved in the MEK-MAPK and apoptotic pathways. Transfection study was performed to assess the role of MEK-MAPK pathway in growth and survival of liver cancer cells. RESULTS: We report that phosphorylation of MEK1/2 at Ser217/221 was detected by immuno-histochemistry in 100% (46 of 46) of HCCs examined. A positive signal was localized in the nuclei of hepatocarcinoma cells but not in dysplastic hepatocytes or stromal cells. Over-expression and phosphorylation of MAPK was also detected in 91% (42 of 46) and 69% (32 of 46) of HCCs examined, respectively. The percentage of cells showing positively for phosphorylated MEK1/2 increased with advancing tumor stage. In vitro, treatment of human HepG2 and Hep3B cells with MEK1/2 specific inhibitors U0126 and PD98059 led to growth inhibition and apoptosis. U0126 induced the release of cytochrome c and increased the cleavage of caspase-3, caspase-7, and poly ADP-ribose polymerase (PARP). Inhibition of phosphatidylinositol 3-kinase (PI-3K), c-Jun N-terminal kinase (JNK) and p38 kinase activities caused only a mild apoptosis in HepG2 and Hep3B cells. Activated MEK1-transfected cells were more resistant to UO126-induced apoptosis in vitro and formed larger tumors in SCID mice than mock-transfected cells. CONCLUSION: In conclusion, our results demonstrate that MEK-MAPK plays an important role in the growth and survival of liver cancer cells and suggest that blocking MEK-MAPK activity may represent an alternative approach for the treatment of liver cancer

Angioimmunoblastic T-cell Lymphoma: A Mimic for Lupus

New-onset systemic lupus erythematosus (SLE) is uncommon in elderly patients. We report the case of a 71-year-old woman who was diagnosed with SLE based on clinical manifestations of fever, alopecia, bicytopenia, hepatomegaly, lymphadenopathy, glomerulonephritis, positive antinuclear antibody (ANA) and anti-double stranded DNA (anti-dsDNA) antibody. Renal biopsy was consistent with lupus nephritis and excision biopsy of a right inguinal lymph node was initially reported as having features of reactive hyperplasia. However, a more careful review of the lymph node biopsy subsequently confirmed a concurrent angioimmunoblastic T-cell lymphoma. This case illustrates the importance of investigating secondary causes and possible alternative diagnoses in patients who present with atypical features of connective tissue disease, and the challenges in diagnosing a rare form of lymphoma

The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours.

The fifth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO "Blue Book"), published in 2022, contains significant revisions. This review summarises the most relevant changes for renal, penile, and testicular tumours. In keeping with other volumes in the fifth edition series, the WHO classification of urogenital tumours follows a hierarchical classification and lists tumours by site, category, family, and type. The section "essential and desirable diagnostic criteria" included in the WHO fifth edition represents morphologic diagnostic criteria, combined with immunohistochemistry and relevant molecular tests. The global introduction of massive parallel sequencing will result in a diagnostic shift from morphology to molecular analyses. Therefore, a molecular-driven renal tumour classification has been introduced, taking recent discoveries in renal tumour genomics into account. Such novel molecularly defined epithelial renal tumours include SMARCB1-deficient medullary renal cell carcinoma (RCC), TFEB-altered RCC, Alk-rearranged RCC, and ELOC-mutated RCC. Eosinophilic solid and cystic RCC is a novel morphologically defined RCC entity. The diverse morphologic patterns of penile squamous cell carcinomas are grouped as human papillomavirus (HPV) associated and HPV independent, and there is an attempt to simplify the morphologic classification. A new chapter with tumours of the scrotum has been introduced. The main nomenclature of testicular tumours is retained, including the use of the term "germ cell neoplasia in situ" (GCNIS) for the preneoplastic lesion of most germ cell tumours and division from those not derived from GCNIS. Nomenclature changes include replacement of the term "primitive neuroectodermal tumour" by "embryonic neuroectodermal tumour" to separate these tumours clearly from Ewing sarcoma. The term "carcinoid" has been changed to "neuroendocrine tumour", with most examples in the testis now classified as "prepubertal type testicular neuroendocrine tumour"

Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma

<p>Abstract</p> <p>Background</p> <p>Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC.</p> <p>Methods</p> <p>Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors.</p> <p>Results</p> <p>A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities.</p> <p>Conclusions</p> <p>Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.</p