Routine elastin staining improves venous invasion detection in colorectal carcinoma.

BACKGROUND: Colorectal carcinoma is the second most common cause of cancer-related deaths in North America. Invasion of tumor cells into lymphatic and blood vessels is an imperative step in the metastatic progression of colorectal carcinoma. OBJECTIVES: This is a before-and-after study conducted by the Department of Pathology and Laboratory Medicine of Mount Sinai Medical Center of Florida to assess the impact on venous invasion (VI) detection by implementing routine elastin staining on all tumor-containing blocks per case, where feasible, in colorectal carcinoma (CRC) resection specimens. METHODS: Clinicopathological parameters of CRC specimens were collected from January until December 2021 (n = 93) for the pre-implementation cohort and from January until December 2022 (n = 61) for the post-implementation cohort. RESULTS: VI detection was significantly increased in the post-implementation cohort at a rate of 50.8 % compared to only 18.6 % in the pre-implementation cohort. The majority of VI identified in the pre-implementation cohort was extramural (61.5 %), whereas in the post-implementation cohort it was intramural (41.9 %). On univariate analysis, implementation of routine elastin stain was associated with strikingly increased VI detection rates (OR = 4.5, p-value < 0.001). On multivariate analysis, after adjusting for other clinicopathologic variables, elastin staining retained its independent statistically significant impact on VI detection (OR = 2.6, p-value = 0.034). Of note, there were no significant differences in the pre- and post-implementation cohorts in the frequency of nodal metastases, tumor extent, histologic grade, perineural invasion, T stage or M stage. CONCLUSION: Based on our results and what has been published recently, we confirm an increase in the VI detection rate after implementing routine elastin staining on all tumor-containing blocks in CRC resection specimens.

Clinicopathological analysis of recurrence and progression of low-grade papillary urothelial carcinoma of the urinary bladder: Predicting the outcome.

BACKGROUND: Urothelial carcinoma of the urinary bladder is the most common malignancy of the urinary system. Patients with low grade papillary urothelial carcinoma (LGPUC) usually have a low risk for tumor recurrence and progression; yet a subset of patients develop recurrence or grade/stage progression to high-grade papillary urothelial carcinoma (HGPUC). The clinicopathological and molecular factors that contribute to this progression are yet to be determined. OBJECTIVES: In our study, we aimed to assess the incidence and clinicopathological factors associated with tumor recurrence/progression of LGPUC. METHODS: Using a pathological database of surgical specimens from patients who underwent bladder biopsies and/or transurethral resection of bladder tumors (TURBTs) between August 01, 2011, and July 31, 2021, at a large academic medical center, a single-center retrospective cohort analysis was performed, and medical charts of patients were reviewed. RESULTS: Of the total 258 patients included, 157 (60.9 %) had "no recurrence", 85 (32.9 %) had ≥1 "recurrence of LGPUC", and 16 (6.2 %) had "grade progression to HGPUC". The mean follow-up time was 31.5 ± 32 months. Patients with "grade progression" and "recurrence of LGPUC" had larger mean tumor size on initial biopsy and multiple lesions on initial cystoscopy compared to those with "no recurrence." Interestingly, former smokers had 2.5- and 8.5-times higher risk of recurrence of LGPUC and grade progression, respectively. CONCLUSION: Since the majority of our patients did not develop recurrence, we question whether there is tendency to overclassify the papillomas as LGPUC based on the 2004 WHO/ISUP consensus grading classification.

Rising incidence of appendiceal neoplasms over time: Does pathological handling of appendectomy specimens play a role?

BACKGROUND: Appendectomy is the most common emergent surgical procedure. Primary appendiceal neoplasms are rare entities that are usually detected incidentally in less than 2% of all appendectomies. The increase in the incidence rates of appendiceal neoplasms over time raises the question whether there is an actual change in the disease occurrence or is it a matter of increased recognition and reporting of what would have been previously missed and undiagnosed. OBJECTIVES: In our study, we aimed to review the archived tissue specimens of patients who were diagnosed with appendiceal neoplasms during the past decade at our institution and compare our clinical experience with published data to identify possible reasons that contribute to the increase in incidence rates of such neoplasms over the past few years. METHODS: Using a pathological database of surgical specimens from patients who underwent appendectomies between January 01, 2010 and September 30, 2020 at a large academic medical center, a single-center retrospective cohort analysis was performed, and medical charts of patients were reviewed. RESULTS: Of the total 1568 patients included, 102 (6.5%) had appendiceal neoplasms divided between primary (79.4%) and secondary/metastatic (20.6%) neoplasms. Annual incidence of appendiceal neoplasms over the past 10 years in our institution demonstrated an increasing trend from 5.6% in 2010 to 12.7% in 2020, which we hypothesize might be attributed to submitting more representative sections of the appendix for pathological examination than we had previously. Our results also showed that 2.8% of patients initially presenting with a typical clinical picture of acute appendicitis had appendiceal neoplasms as a truly incidental finding, while 20.3% of patients who underwent elective appendectomies for a suspicious appendiceal mass were found to be neoplastic. Interestingly, among the 80 cases of epithelial neoplasms, more non-carcinoid neoplasms were detected than carcinoid tumors. CONCLUSION: Based on our results and what has been published recently, we confirm an additional increase in incidental appendiceal neoplasms found in appendectomies performed for a clinical picture of acute appendicitis, which may be related to more thorough specimen assessment. Whether this is clinically impactful remains to be determined. However, these data support a modification in the way appendectomy specimens are handled in pathology labs post-operatively.

Morphological and immunophenotypical analysis of the spindle cell component in adenomyomatous hyperplasia of the gallbladder.

BACKGROUND: Adenomyomatous hyperplasia (AMH) of the gallbladder, reported in 1-8.7% of cholecystectomies, consists of cystically dilated sinuses/glands with a surrounding spindle cell proliferation which is thought to be composed of smooth muscle cells. Myofibroblasts are contractile cells that secrete a variety of biochemical modulators causing a "field-effect". Myofibroblasts can be immunohistochemically distinguished from smooth muscle cells by their desmin negativity. METHODS: Eighteen cases of AMH and five cases each of chronic follicular cholecystitis, chronic cholecystitis, gallbladder carcinoma and 10 colonic diverticular disease were stained with actin and desmin. The percentage of myofibroblasts was estimated by the difference between actin and desmin staining in the same field. Statistical anlysis was performed using SPSS 22.0. RESULTS: The percentage of actin staining was significantly higher in AMH and gallbladder carcinoma compared to chronic follicular and chronic cholecystitis (p = 0.04). The percentage of desmin staining did not show any significant difference between the four groups. The estimated myofibroblastic population was significantly higher in AMH when compared to chronic follicular and chronic cholecystitis (p = 0.005). CONCLUSION: The spindle cell proliferation around cystically dilated glands in AMH is composed predominantly of myofibroblasts and of smooth muscle cells as previously described. This finding suggest a derangement in epithelial-stromal interactions as the underlying pathophysiology in AMH.

Clinical, histopathologic, and immunoarchitectural features of dermatopathic lymphadenopathy: an update.

Dermatopathic lymphadenopathy is a distinctive form of paracortical lymph node hyperplasia that usually occurs in the setting of chronic dermatologic disorders. The aim of this study is to update our understanding of the clinicopathologic and immunophenotypic features of dermatopathic lymphadenopathy. The study cohort was 50 lymph node samples from 42 patients diagnosed with dermatopathic lymphadenopathy. The patients included 29 women and 13 men with a median age of 49 years (range, 12-79). Twenty-two (52%) patients had a dermatologic disorder, including mycosis fungoides (n = 6), chronic inflammatory dermatoses (n = 13), melanoma (n = 1), squamous cell carcinoma (n = 1), and Kaposi sarcoma in the context of human immunodeficiency virus infection (n = 1). Twenty (48%) patients did not have dermatologic manifestations. Lymph node biopsy specimens were axillary (n = 22), inguinal (n = 21), cervical (n = 4), and intramammary (n = 3). All lymph nodes showed paracortical areas expanded by lymphocytes; dendritic cells, including interdigitating dendritic cells and Langerhans cells; and macrophages. Melanophages were detected in 48 (98%) lymph nodes. Immunohistochemical analysis provided results that are somewhat different from those previously reported in the literature. In the paracortical areas of lymph node, S100 protein was expressed in virtually all dendritic cells, and CD1a was expressed in a significantly greater percentage of cells than langerin (80 vs. 35%, p < 0.0001). These results suggest that the paracortical regions of dermatopathic lymphadenopathy harbor at least three immunophenotypic subsets of dendritic cells: Langerhans cells (S100+, CD1a+(high), langerin+), interdigitating dendritic cells (S100+, CD1a+(low), langerin-), and a third (S100+, CD1a-, langerin-) minor population of dendritic cells. Furthermore, in more than 60% of dermatopathic lymph nodes, langerin highlighted trabecular and medullary sinuses and cords, showing a linear and reticular staining pattern, which could be a pitfall in the differential diagnosis with Langerhans cell histiocytosis involving lymph nodes.

Tracheal agenesis with esophageal atresia: an autopsy case report of a variant incompatible with life.

Background: Tracheal agenesis/atresia (TA) presents with respiratory distress at birth and subsequent difficulty in endotracheal intubation. The antenatal course is complicated by polyhydramnios and premature labor. Case report: We present a newborn baby boy with respiratory distress and unsuccessful intubation. Postmortem neck dissection revealed tracheal atresia with esophageal atresia and high tracheoesophageal fistula. Conclusion: In this variant of tracheal atresia, the coexistent esophageal atresia precluded the establishment of a functional air passage. This variant that does not fall into the any of the described categories in accepted classification systems. The lack of any distal communication makes this case inoperable and fatal.

Cholangitis Lenta Causing Bile Cast Nephropathy: A Unique Model of Hepatorenal Failure in Sepsis.

INTRODUCTION: Inadequate perfusion and abnormal cellular metabolism are among the mechanisms of organ dysfunction in sepsis. Concomitant hepatorenal failure during the late phase of sepsis is poorly understood. CASE REPORT: The autopsy of a child who developed sepsis-induced hepatorenal failure revealed bile cast nephropathy, hepatic centrilobular necrosis and cholangitis lenta, a type of sepsis-induced cholestasis, with no biliary obstruction, fibrosis or cirrhosis. The liver and renal function declined at the same rate as procalcitonin increased. DISCUSSION: Failure of resolution and persistent inflammation in sepsis can result in ductular injury and stagnation of bile with subsequent cholemia. The kidney failure was associated with the formation of intratubular bile casts. CONCLUSION: This case illustrates how severe cholestasis in combination with bile cast nephropathy may be potential and unrecognized contributors to hepatorenal failure in sepsis. Whether bile toxicity causes renal failure in the context of cholangitis lenta should be further studied.

Constitutive Notch Signaling Causes Abnormal Development of the Oviducts, Abnormal Angiogenesis, and Cyst Formation in Mouse Female Reproductive Tract.

The Notch signaling pathway is critical for the differentiation of many tissues and organs in the embryo. To study the consequences of Notch1 gain-of-function signaling on female reproductive tract development, we used a cre-loxP strategy and Amhr2-cre transgene to generate mice with conditionally activated Notch1 (Rosa(Notch1)). The Amhr2-cre transgene is expressed in the mesenchyme of developing female reproductive tract and in granulosa cells in the ovary. Double transgenic Amhr2-cre, Rosa(Notch1) females were infertile, whereas control Rosa(Notch1) mice had normal fertility. All female reproductive organs in mutants showed hemorrhaging of blood vessels progressing with age. The mutant oviducts did not develop coiling, and were instead looped around the ovary. There were multiple blockages in the lumen along the oviduct length, creating a barrier for sperm or oocyte passage. Mutant females demonstrated inflamed uteri with increased vascularization and an influx of inflammatory cells. Additionally, older females developed ovarian, oviductal, and uterine cysts. The significant change in gene expression was detected in the mutant oviduct expression of Wnt4, essential for female reproductive tract development. Similar oviductal phenotypes have been detected previously in mice with activated Smo and in beta-catenin, Wnt4, Wnt7a, and Dicer conditional knockouts, indicating a common regulatory pathway disrupted by these genetic abnormalities.

Comparison of Performance Characteristics of Oval Cup Forceps Versus Serrated Jaw Forceps in Gastric Biopsy.

BACKGROUND: Obtaining quality endoscopic biopsy specimens is vital in making successful histological diagnoses. The influence of forceps cup shape and size on quality of biopsy specimens is unclear. AIM: To identify whether oval cup or two different serrated jaw biopsy forceps could obtain specimens of superior size. Secondary endpoints were tissue adequacy, depth of tissue acquisition, and crush artifact. METHODS: A single-center, prospective, pathologist-masked, randomized controlled trial was performed. In total 136 patients with a clinical indication for esophagogastroduodenoscopy with biopsy were randomized to receive serial biopsies with a large-capacity serrated forceps with jaw diameter 2.2 mm (SER1) and either a large-capacity oval forceps with jaw diameter 2.4 mm (OVL) or large-capacity serrated biopsy forceps with jaw diameter 2.4 mm (SER2) in two parallel groups. RESULTS: SER2 provided significantly larger specimens than did the other forceps (SER2 3.26 ± 1.09 vs. SER1 2.92 ± 0.88 vs. OVL 2.92 ± 0.76; p = 0.026), with an average size difference of 0.34 mm greater with SER2 compared to SER1 and OVL. OVL provided significantly deeper biopsies compared to SER1 and SER2 (p = 0.02), with 31 % of OVL biopsies reaching the submucosa. SER2 had significantly less crush artifact than SER1 and OVL (p < 0.0001). CONCLUSION: Serrated forceps provided larger samples compared to oval jaw forceps of the same size, with SER2 providing the largest specimen size. Oval cup forceps had deeper penetration of epithelium, while the larger jaw diameter serrated jaw forceps had less crush artifact. All three forceps provided specimens adequate for diagnostic purposes.

Oncocytoma of the adrenal gland medulla.

We report an unprecedented case of an oncocytoma of the adrenal gland medulla in a 61-year-old woman. The patient presented with right flank pain and hematuria. Computed tomographic studies revealed a right adrenal gland mass that measured 2 cm, which was subsequently excised laparoscopically. Grossly, the tumor in the medulla measured 1.9 × 1.2 cm, weighed 5 g, and had a solid tan-brown cut surface. Histologically, it consisted of large tumor cells containing eosinophilic granular cytoplasm arranged in trabecular and nodular patterns. Electron microscopy revealed closely packed mitochondria in the cytoplasm of almost all tumor cells. The tumor cells were immunohistochemically positive for vimentin. The patient resumed usual activities 2 weeks after surgery, and at 6-month follow-up, she is doing well.

Repurposing of Anticancer Stem Cell Drugs in Brain Tumors.

Brain tumors in adults may be infrequent when compared with other cancer etiologies, but they remain one of the deadliest with bleak survival rates. Current treatment modalities encompass surgical resection, chemotherapy, and radiotherapy. However, increasing resistance rates are being witnessed, and this has been attributed, in part, to cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells that reside within the tumor bulk and have the capacity for self-renewal and can differentiate and proliferate into multiple cell lineages. Studying those CSCs enables an increasing understanding of carcinogenesis, and targeting CSCs may overcome existing treatment resistance. One approach to weaponize new drugs is to target these CSCs through drug repurposing which entails using drugs, which are Food and Drug Administration-approved and safe for one defined disease, for a new indication. This approach serves to save both time and money that would otherwise be spent in designing a totally new therapy. In this review, we will illustrate drug repurposing strategies that have been used in brain tumors and then further elaborate on how these approaches, specifically those that target the resident CSCs, can help take the field of drug repurposing to a new level.

Medulloblastoma cancer stem cells: molecular signatures and therapeutic targets.

Medulloblastoma (MB) is the most common malignant primary intracranial neoplasm diagnosed in childhood. Although numerous efforts have been made during the past few years to exploit novel targeted therapies for this aggressive neoplasm, there still exist substantial hitches hindering successful management of MB. Lately, progress in cancer biology has shown evidence that a subpopulation of cells within the tumour, namely cancer stem cells (CSCs), are thought to be responsible for the resistance to most chemotherapeutic agents and radiation therapy, accounting for cancer recurrence. Hence, it is crucial to identify the molecular signatures and genetic aberrations that characterise those CSCs and develop therapies that specifically target them. In this review, we aim to give an overview of the main genetic and molecular cues that depict MB-CSCs and provide a synopsis of the novel therapeutic approaches that specifically target this population of cells to attain enhanced antitumorous effects and therefore overcome resistance to therapy.

Retinoblastoma co-repressor 1 (RB) and cyclin-dependent kinase inhibitor (CDKN) as a multi-gene panel for differentiating pulmonary from non-pulmonary origin in metastatic neuroendocrine carcinomas.

BACKGROUND: Neuroendocrine carcinomas (NECs) arise from neuroendocrine cells present throughout the body, and often present with metastases even with small and undetectable primary tumors. Additionally, neuroendocrine differentiation can be seen in carcinomas of non-neuroendocrine origin further complicating the landscape of metastatic NECs. Organ specific immunohistochemical markers such as TTF1, CDX2 and PAX8 are often lost in high grade tumors and may be non-contributory in localizing the primary site. Though NECs share a common cellular origin, they exhibit great variability in biologic behavior, prognosis and treatment based on the primary organ of origin. DESIGN: Twenty one cases of metastatic NECs were retrieved from our archives and were classified based on location of the primary tumor derived from clinical and radiological findings. Next generation sequencing data was retrieved and analyzed for recurrent genetic abnormalities in these cases. Statistical analysis was performed using IBM SPSS25 software. RESULTS: RB1 mutations were exclusive to NECs metastasizing from lung primary and were detected in 5 of 12 (41.6 %) cases (p = 0.04). CDKN gene family (CDKN1B and 2 A) mutations were limited to metatstatic NECs of non-pulmonary origin and were detected in 4 of 9 (44.4 %) cases (p = 0.02). CONCLUSION: The location of the primary tumor in metastatic NECs appears to have significant prognostic and therapeutic implications. But due to the morphological homogeneity, higher grade of tumor, variable sensitivity of immunohistochemical markers, and small, often undetectable primary tumors, the localization of the primary tumor in cases of metastatic NECs is a challenge. In this study, RB1 and CDKN gene family mutations are identified as possible markers for differentiating pulmonary and non-pulmonary origin in metatstatic NECs.

Magnetic resonance imaging-ultrasound fusion-targeted biopsy combined with systematic 12-core ultrasound-guided biopsy improves the detection of clinically significant prostate cancer: Are we ready to abandon the systematic approach?

BACKGROUND: Multiparametric (mp) magnetic resonance imaging (MRI)-ultrasound fusion-targeted biopsy (TB) has improved the detection of clinically significant prostate cancer (csCaP) using the Prostate Imaging Reporting and Data System (PI-RADS) reporting system, leading some authors to conclude that TB can replace the 12-core systematic biopsy (SB). We compared the diagnostic performance of TB with SB at our institution. METHODS: Eighty-three men with elevated prostate-specific antigen levels (6.6 ng/mL, interquartile range [IQR] 4.5-9.2) and abnormal mp-MRI (127 lesions, PI-RADS ≥3, median size: 1.1 cm, IQR 0.8-1.6) underwent simultaneous TB and SB. Diagnosis of any CaP (Gleason score, [GS] ≥6) and csCaP (GS ≥7) was compared using the McNemar's exact test. RESULTS: SB showed higher, but not statistically significant, detection rates of any CaP and csCaP (51.8% and 34.9%) versus TB (44.6% and 28.9%) (P = 0.286 and P = 0.359, respectively). TB outperformed SB in the quantification of 56.6% CaP and detecting cancer in anterior sectors (7.2%). Compared to SB, TB missed twice the amount of any CaP and csCaP. SB alone detected 22.2% of all csCaPs and upgraded 20.6% of TB-detected CaP. SB identified cancer invisible on mp-MRI (13.7% of all CaP) or missed by TB due to a small size (<1 cm) and sampling error (7% of lesions). CONCLUSION: A combination of SB with TB remained necessary for achieving the highest cancer detection rates. Limiting prostate biopsy to TB alone can miss csCaP due to the presence of synchronous high-grade cancer invisible on MRI or failure to hit the target. TB is the best approach for anterior lesions and tumor quantification.

Low-Grade Ductal Carcinoma In Situ.

OBJECTIVES: We aimed to determine the interobserver reproducibility in diagnosing low-grade ductal carcinoma in situ (DCIS). We also aimed to compare the interobserver variability using a proposed two-tiered grading system as opposed to the current three-tiered system. METHODS: Three expert breast pathologists and one junior pathologist identified low-grade DCIS from a set of 300 DCIS slides. Months later, participants were asked to grade the 300 cases using the standard three-tiered system. RESULTS: Using the two-tiered system, interobserver agreement among breast pathologists was considered moderate (κ = 0.575). The agreement was similar (κ = 0.532) with the junior pathologist included. Using the three-tiered system, pathologists' agreement was poor (κ = 0.235). CONCLUSIONS: Pathologists' reproducibility on diagnosing low-grade DCIS showed moderate agreement. Experience does not seem to influence reproducibility. Our proposed two-tiered system of low vs nonlow grade, where the intermediate grade is grouped in the nonlow category has shown improved concordance.

Significance of periductal lymphatic and blood vascular densities in intraductal carcinoma of the breast.

We investigated the significance of periductal lymphatic and blood vascular densities in intraductal carcinomas (IDC) of the breast. Thirty five cases of pure IDC treated by partial or total mastectomy were reviewed. Seven cases with normal breast tissue and 48 cases of invasive breast carcinoma were included as controls. All cases were immunostained with D2-40 and CD31. Positively stained microvessels were counted in densely vascular/lymphatic foci (hot spots) at 400x (=0.17 mm(2)) in the periductal areas. IDC without comedonecrosis showed a mean periductal D2-40 lymphatic microvessel density (LMD) of 5.8 +/- 5 (range 0-18), and a CD31 microvessel density (MD) of 14 +/- 8.9 (range 1-40). IDC with comedonecrosis showed periductal D2-40 LMD of 8.4 +/- 3.8 (range 4-18), and a CD31 MD of 24.3 +/- 7.6 (range 14-40). There was a significant difference between periductal D2-40 LMD and CD31 MD counts in IDC with and without comedonecrosis. There was a positive correlation of periductal D2-40 LMD and CD31 MD counts with high nuclear grade (r = 0.39 and 0.56) of IDC as well as with the presence of comedonecrosis (r = 0.49 and 0.59). Both D2-40 LMD and CD31 MD did not correlate significantly with tumor size, estrogen status, or progesterone status. As IDC with comedonecrosis and/or high nuclear grade has a worse prognosis than IDC without comedonecrosis and/or with low nuclear grade, it appears that lymphatic and blood vascular density evaluated by D2-40 and CD31, respectively, are independent prognostic indicators for patients with IDC of the breast and may be an indicator of early or unrecognized invasion or "regression."

Congenital acinar dysplasia: a lethal entity.

Congenital acinar dysplasia is a lethal, developmental lung malformation resulting in neonatal respiratory insufficiency. This entity is characterized by pulmonary hypoplasia and arrest in the pseudoglandular stage of development, resulting in the absence of functional gas exchange. The etiology is unknown, but a relationship with the disruption of the TBX4-FGF10 pathway has been described. There are no definitive antenatal diagnostic tests. It is a diagnosis of exclusion from other diffuse embryologic lung abnormalities with identical clinical presentations that are, however, histopathologically distinct.

A clinicopathological study of fibroadenomas with epithelial proliferation including lobular carcinoma in-situ, atypical ductal hyperplasia, DCIS and invasive carcinoma.

BACKGROUND: Fibroadenoma is a benign mixed tumor composed of epithelial and non-epithelial components. The epithelial component of a fibroadenoma may exhibit proliferation, including lobular carcinoma in-situ, atypical ductal hyperplasia, DCIS and rarely, invasive breast carcinoma. OBJECTIVE: In this series of 30 cases of fibroadenoma with epithelial proliferation, we assessed the radiological and histopathological findings of each entity. METHOD: A retrospective review was performed to identify all fibroadenomas diagnosed at our institution between January 2012 and May 2018. RESULTS: In a total of 1523 consecutive cases of fibroadenomas, thirty cases had epithelial proliferations with an overall prevalence of 1.97%. Eight cases had fibroadenoma with lobular carcinoma in-situ, six cases had atypical ductal hyperplasia, ten cases had DCIS and six cases had invasive carcinoma. In cases of fibroadenomas with lobular carcinoma in-situ, 62.5% of the cases the neoplasia was confined to the fibroadenoma whereas only 10% of the cases with DCIS showed confinement to the fibroadenoma (p = 0.036). The most common radiological finding was the presence of a mass. The BI-RADS scores were 4 and above in all cases (p > 0.05). CONCLUSION: In our study population, the most common type of carcinoma arising in fibroadenomas was DCIS, followed by lobular carcinoma in-situ. Lobular carcinoma in-situ was more likely to be confined to the fibroadenoma while most DCIS involved surrounding breast tissue.

Liver Fibrosis Helps to Distinguish Autoimmune Hepatitis from DILI with Autoimmune Features: A Review of Twenty Cases.

Background and Aims: Drug-induced liver injury with autoimmune features (AI-DILI) mimics the clinical presentation, and laboratory and pathologic features of idiopathic autoimmune hepatitis (AIH). We aimed to identify histopathologic hallmarks to differentiate these entities. Methods: All liver biopsies archived for the past 10 years were reviewed retrospectively to identify cases of recently detected liver injury associated with predominantly lymphoplasmacytic interphase hepatitis, positive markers for liver autoimmunity, and negative tests for viral hepatitis. Twenty cases were divided into AIH (n = 12) or AI-DILI (n = 8) groups. Blind qualitative evaluation of necroinflammatory changes and liver fibrosis were performed according to the Scheuer scoring system. Cellular densities were determined using ImageJ (V1.51t, National Institutes of Health, Bethesda, MD, USA). Fibrosis was assessed on Masson trichrome-stained slides, and collagen deposition was estimated following a protocol of color deconvolution. Results: Necroinflammatory changes as well as densities (portal and lobular) of neutrophils and eosinophils, intracellular cholestasis, and regenerative changes did not differ between the two groups (P ≥ 0.05). Neutrophil densities but not eosinophils showed a positive correlation with the severity of hepatocellular damage (r = 0.6 and 0.58, vs. alanine aminotransferase, P < 0.05). Ceroid-laden macrophages but not histiocytic aggregates appeared to be more common in AI-DILI (P < 0.05). AIH patients presented more often with evidence of chronic damage, including higher scores of fibrosis and collagen deposition, in comparison to AI-DILI (P < 0.05). Conclusions: Although there is no histologic feature pathognomonic for AI-DILI or AIH, advanced stages of liver fibrosis can be used to support the diagnosis of AIH in some cases. Definitive diagnosis of AI-DILI requires follow-up and demonstration of complete remission after drug withdrawal with no need for immunosuppression.