The Usefulness of Elastin Staining to Detect Vascular Invasion in Cancer.

Tumor prognosis hinges on accurate cancer staging, a pivotal process influenced by the identification of lymphovascular invasion (LVI), i.e., blood vessel and lymphatic vessel invasion. Protocols by the College of American Pathologists (CAP) and the World Health Organization (WHO) have been established to assess LVI in various tumor types, including, but not limited to, breast cancer, colorectal cancer (CRC), pancreatic exocrine tumors, and thyroid carcinomas. The CAP refers to blood vessel invasion as "angioinvasion" (vascular invasion) to differentiate it from lymphatic vessel invasion (lymphatic invasion). For clarity, the latter terms will be used throughout this review. The presence of lymphatic and/or vascular invasion has emerged as a pivotal prognostic factor; therefore, its accurate identification is crucial not only for staging but also for providing the patient with an honest understanding of his/her prognosis. Given the prognostic importance of the correct identification of LVI, specific staining techniques are employed to distinguish lymphatic vessel invasion from angioinvasion and to differentiate true LVI from artifact. These encompass hematoxylin and eosin (H&E) staining, elastic staining, Factor VIII staining, Ulex europaeus I agglutinin staining, CD31, CD34, D2-40, ERG, and D2-40 (podoplanin) immunohistochemical (IHC) stains among others. Based on a review of numerous publications regarding the efficacy of various methods for LVI detection, elastin staining demonstrated superior accuracy and prognostic value, allowing for more targeted treatment strategies. The clinical significance of accurately detecting LVI cannot be overstated, as it is strongly linked to higher cancer-related mortality and an increased risk of tumor recurrence. This review aims to examine the existing literature on the use of elastin stains in the detection of vascular invasion among different types of tumors and its prognostic value.

Brenner Tumor of the Ovary: A 10-Year Single Institution Experience and Comprehensive Review of the Literature.

Brenner tumors (BTs) are surface-epithelial stromal cell tumors that are categorized by the World Health Organization as benign, borderline, and malignant. Due to the rarity of BTs, the published literature on these tumors is comprised primarily of case reports and small retrospective studies. We performed a pathology database review spanning the last ten years at our institution revealing nine reported benign BTs. We collected the clinical and pathological data of patients associated with those BTs, describing the clinical presentation and imaging results, and assessing the possible risk factors associated with them. The average age at diagnosis was 58 years. BTs were discovered incidentally in 7/9 cases. The tumor was multifocal and bilateral in 1/9 cases and ranged in size from 0.2 cm to 7.5 cm. Associated Walthard rests were found in 6/9 cases and transitional metaplasia of surface ovarian and/or tubal epithelium was found in 4/9 cases. One patient had an associated mucinous cystadenoma in the ipsilateral ovary. Another patient had an associated mucinous cystadenoma in the contralateral ovary. In conclusion, we found that Walthard rests and transitional metaplasia are common findings in association with BTs. Additionally, pathologists and surgeons need to be aware of the association between mucinous cystadenomas and BTs.

Drug Repurposing in Non-Small Cell Lung Carcinoma: Old Solutions for New Problems.

Lung cancer is the second most common cancer and the leading cause of cancer-related deaths in 2022. The majority (80%) of lung cancer cases belong to the non-small cell lung carcinoma (NSCLC) subtype. Despite the increased screening efforts, the median five-year survival of metastatic NSCLC remains low at approximately 3%. Common treatment approaches for NSCLC include surgery, multimodal chemotherapy, and concurrent radio and chemotherapy. NSCLC exhibits high rates of resistance to treatment, driven by its heterogeneity and the plasticity of cancer stem cells (CSCs). Drug repurposing offers a faster and cheaper way to develop new antineoplastic purposes for existing drugs, to help overcome therapy resistance. The decrease in time and funds needed stems from the availability of the pharmacokinetic and pharmacodynamic profiles of the Food and Drug Administration (FDA)-approved drugs to be repurposed. This review provides a synopsis of the drug-repurposing approaches and mechanisms of action of potential candidate drugs used in treating NSCLC, including but not limited to antihypertensives, anti-hyperlipidemics, anti-inflammatory drugs, anti-diabetics, and anti-microbials.

Diffuse pulmonary ossification: A case report unveiling clinical and histopathological challenges.

Diffuse pulmonary ossification (DPO) is a rare pulmonary condition characterized by the diffuse formation of mature bone in the lungs. Pulmonary ossification, in general, can be subdivided into diffuse pulmonary ossification (DPO) and nodular pulmonary ossification (NPO). DPO occurs most commonly in the settings of chronic pulmonary conditions; however, idiopathic cases have been reported. We present a case of DPO in a 36-year-old man with progressive exertional dyspnea, productive cough, and occasional hemoptysis. Imaging studies showed innumerable pulmonary nodules scattered throughout both lungs. Initially, the diagnoses of pulmonary alveolar microlithiasis (PAM) or, less likely miliary tuberculosis (TB) were considered. However, Quantiferon TB test was negative and genetic testing was negative for SLC34A2, lowering the probability of PAM. The patient underwent a segmentectomy. Microscopic examination showed ramifying spicules of mature woven bone and fatty marrow consistent with DPO. There were no significant underlying pathologic findings, such as interstitial fibrosis, granulomas, organizing pneumonia, or significant inflammation in the background lung parenchyma. In conclusion, clinicians and radiologists need to be aware of DPO in the differential diagnosis of miliary tuberculosis and pulmonary alveolar microlithiasis. The absence of an underlying chronic pulmonary condition does not exclude the possibility of DPO.

Neonatal acute liver failure with pulmonary yellow hyaline membrane and kernicterus.

BACKGROUND: Neonatal acute liver failure (NALF) is a rare and life-threatening condition. It causes bilirubin to accumulate to a dangerous level in the body, causing permanent damage to vital organs such as the brain and lungs. In many cases, the etiology of NALF remains unknown. CASE PRESENTATION: We described a case of an 8-day-old baby girl who presented with poor oral intake, lethargy, and jaundice. Her clinical condition rapidly deteriorated with progression to multi-organ failure, and despite intensive resuscitation efforts, she expired. At autopsy, the most significant findings were liver necrosis, yellow hyaline membrane deposition in the lungs, and bilirubin deposition in the brain (kernicterus). CONCLUSIONS: NALF is a rare and potentially fatal condition necessitating prompt recognition and disease-specific treatment approaches. Toxic accumulation of bilirubin in the lungs can lead to hypoxia and precipitate further ischemic injury to the liver.

Correlation between spread through air spaces (STAS) and other clinicopathological parameters in lung cancer.

BACKGROUND: "Spread through airspace" (STAS) is defined as micropapillary clusters, solid nests or single cells of tumor extending beyond the edge of the tumor into the air spaces of the surrounding lung parenchyma. It is associated with reduced overall survival and disease-free survival. Assessment of STAS in lung cancer appears to be necessary to guide clinical interventions. However, data on the correlation between the status of STAS and other lung cancer clinicopathological parameters are scarce. METHODS: We reviewed 240 resected lung cancers and investigated the clinical significance of STAS in relation to other relevant lung cancer clinicopathological variables. We performed univariate and multivariate logistic regression analyses with STAS as a dependent variable. RESULTS: Of the total 240 patients, STAS was observed in 67 (27.9 %) of them. STAS is highly prevalent in adenocarcinoma with a micropapillary growth pattern (70.0 %) than in other lung cancer growth patterns. STAS was frequently reported in wedge resections (31.0%) than in lobectomy specimens (26.7 %). STAS was significantly associated with advanced pN stage (p < 0.001) and lymphovascular invasion (p = 0.005). In multivariate models, we found that lung cancers in the right lower lobe (RLL) (OR, 2.674; 95 % CI = 1.313-5.448, p = 0.007), micropapillary lung cancer growth pattern (OR = 5.199, 95 % CI = 1.220-22.162, p = 0.026), and pN2 stage (OR = 3.683, 95 % CI = 1.324-10.245, p = 0.013) serve as independent predictors for STAS. CONCLUSION: Our findings suggest that the presence of STAS is associated with right lower lobe tumors, micropapillary adenocarcinoma, and pN2 tumor stage. Hence, it could serve as one of the prognostically significant histologic findings in lung cancer. It is thus valid to mandate reporting STAS status in CAP surgical pathology lung cancer case summaries.

Neonatal acute liver failure with pulmonary yellow hyaline membrane and kernicterus

Background Neonatal acute liver failure (NALF) is a rare and life-threatening condition. It causes bilirubin to accumulate to a dangerous level in the body, causing permanent damage to vital organs such as the brain and lungs. In many cases, the etiology of NALF remains unknown. Case presentation We described a case of an 8-day-old baby girl who presented with poor oral intake, lethargy, and jaundice. Her clinical condition rapidly deteriorated with progression to multi-organ failure, and despite intensive resuscitation efforts, she expired. At autopsy, the most significant findings were liver necrosis, yellow hyaline membrane deposition in the lungs, and bilirubin deposition in the brain (kernicterus). Conclusions NALF is a rare and potentially fatal condition necessitating prompt recognition and disease-specific treatment approaches. Toxic accumulation of bilirubin in the lungs can lead to hypoxia and precipitate further ischemic injury to the liver.

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.

IMP3 expression in serous tumors of the ovary.

Insulin-like growth factor II mRNA-binding protein (IMP3) is an oncofetal protein involved in embryogenesis, which is expressed in a variety of malignant neoplasms. It is rarely expressed in normal adult tissue and benign tumors. The aim of this study was to evaluate the expression of IMP3 in benign and malignant serous tumors of the ovary. Seventy-nine ovarian tumors were examined for IMP3 expression by immunohistochemical analysis, comprising 16 benign serous tumors, 19 borderline serous tumors, and 44 serous carcinomas. Positive staining was defined as brown staining in the cytoplasm. Negative staining was defined as absent staining or staining of <5% of tumor cells. The intensity of staining (weak, moderate, and strong) and percentage (0% to 100%) of neoplastic cells staining positive for cytoplasmic IMP3 staining were recorded in each case. Moderate to strong cytoplasmic staining for IMP3 was observed in 30 of 44 (68%) serous carcinomas of the ovary; in contrast, <5% of the borderline and benign serous tumors expressed IMP3 ranging from weak to strong cytoplasmic staining. Statistically, the difference in IMP3 expression between these groups of tumors was highly significant (P<0.0001). Our findings demonstrate moderate to strong expression of IMP3 in the majority of ovarian serous carcinomas as compared with benign/borderline serous tumors, which demonstrated weak to strong expression in a small minority (<5%) of the tumors. Thus, IMP3 may be a useful adjunctive tool in the pathologic evaluation of ovarian serous tumors.

Serous carcinoma of the ovary and peritoneum with metastases to the breast and axillary lymph nodes: a potential pitfall.

Metastasis of ovarian or peritoneal serous carcinoma to the breast and/or axillary lymph nodes is a rare event. Nevertheless, its recognition and distinction from mammary carcinoma are of great clinical importance because the treatment and prognosis differ significantly. Eighteen cases of ovarian or peritoneal serous carcinoma metastatic to the breast and/or axillary LNs from a 14-year period (1990-2003) were retrieved from our files. Clinical information was obtained from the patients' charts. The age of the patients ranged from 21 to 67 years (median, 55 years). The primary tumors included 14 ovarian serous carcinomas (11 high grade and 3 low grade; 2 of the low-grade tumors presented as serous tumors of low malignant potential and recurred as low-grade serous carcinoma) and 4 peritoneal serous carcinomas (3 high grade and 1 low grade). Of the ovarian neoplasms, 1 was stage I and 10 were stage III tumors; the breast and/or axillary lymph node metastases were discovered on average 30 months after presentation (range, 7-135 months). Three of the ovarian serous carcinomas were stage IV tumors; in 1 case, there were axillary lymph node metastases at initial presentation; and in 2 cases, breast and/or axillary lymph node metastases developed at 18 and 102 months. Two of the 4 patients with peritoneal serous carcinoma presented with stage IV disease, having synchronous breast and axillary lymph node metastases; the other 2 patients developed them at 11 and 16 months after presentation. Four patients had multiple breast lesions and 8 patients had a single metastasis. In 4 cases, the breast metastases were initially interpreted as infiltrating ductal carcinoma. The remaining 6 patients had axillary lymph node involvement only. The metastases in 17 of the cases had papillary features, with psammoma bodies present in 4. Immunoperoxidase studies for GCDFP-15 and WT-1 were performed in 4 cases; all 4 were positive for WT-1 and negative for GCDFP-15. Follow-up was available for 17 patients, with 7 patients known to be dead from disease (survival range, 2-31 months) after the development of metastatic disease to the breast or axillary lymph nodes. Ten patients were alive with disease at their last follow-up, which ranged from 1 to 30 months after the breast or axillary LN metastasis developed. Metastases to the breast or axillary lymph nodes from ovarian and/or peritoneal serous carcinomas are uncommon. Most of the patients in whom metastatic disease develops have a known history of advanced stage ovarian or peritoneal carcinoma. Breast and/or axillary LN involvement at initial presentation can occur but is rare. Differentiation between metastatic and primary tumors of the breast is of great importance because treatment and prognosis differ significantly. Clinical history, the presence of papillary architecture, and WT-1 expression are useful in establishing the correct diagnosis.

Fine-needle aspiration cytology of mucinous tumors of the pancreas.

BACKGROUND: Tumors of the pancreas associated with extracellular mucin production include mucin-producing ductal adenocarcinoma, mucinous cystic neoplasm (MCN), and intraductal papillary mucinous tumor (IPMT). Fine-needle aspiration (FNA) is used as an adjunct to radiologic analysis for the preoperative categorization of these tumors. The current study was designed to identify distinctive cytomorphologic features that would be useful for the categorization of mucinous tumors of the pancreas. METHODS: The authors evaluated Papanicolaou smears and Diff-Quik-stained smears of specimens obtained by computed tomography-guided and endoscopic ultrasound-guided FNA of the pancreas in 51 cases of mucinous tumors. In the 19 cases in which the patients underwent surgical excision after FNA, the cytologic features were compared with the histopathologic findings. The remaining cases were categorized as one of the three above-mentioned types of mucinous tumors on the basis of cytomorphologic features identified as indicative of subtype among the cases in which a cytologic-histologic correlation was performed. RESULTS: Among the 19 cases with cytologic-histologic correlation, 2 cases of serous cystadenoma and 2 cases of gastrointestinal duplication cyst were misdiagnosed on cytologic analysis as low-grade MCN. Among the remaining 15 cases, cytologic features by histologic diagnosis were as follows: ductal adenocarcinoma (n = 4): moderate to high cellularity, mild to moderate background mucin, three-dimensional clusters, high nuclear cytoplasmic ratios, and mild to moderate nuclear membrane irregularities; low-grade MCN (n = 5): mild to moderate cellularity, abundant background mucin, small clusters, and flat sheets of relatively bland glandular cells; mucinous cystadenocarcinoma (n = 1): similar to ductal adenocarcinoma but more abundant background mucin; and IPMT (n = 5): moderate to high cellularity, abundant background mucin, and prominent papillary arrangement of tall columnar cells with mild to moderate nuclear atypia. The remaining 32 cases were categorized based on cytology alone as adenocarcinoma with mucin production (n = 24) and low-grade MCN (n = 8). CONCLUSIONS: IPMT and low-grade MCN possess distinctive cytologic features that can be used to diagnose them correctly and distinguish them from one another and from other cystic tumors. Duplication cysts closely mimic low-grade MCN, which can lead to false-positive diagnoses. Because of substantial overlap in cytologic features, mucin-producing ductal adenocarcinoma was unable to be distinguished from mucinous cystadenocarcinoma cytologically.

Tubular carcinoma of the breast: an institutional experience and review of the literature.

Tubular carcinoma of the breast is a variant of invasive ductal carcinoma that is well differentiated and characterized by an orderly tubular formation. Although often perceived to have a better prognosis, there continues to be questions regarding the extent of treatment required. A retrospective review of 44 patients diagnosed with tubular carcinoma of the breast from 1987 to 1999 was performed. All documented data regarding patient and tumor characteristics plus the extent of treatment were analyzed and compared. Lymph node metastases were present in 4 of 32 patients (13%) who had nodes examined. Tumor size correlated with axillary status, with tumors less than 15 mm having no axillary nodal involvement. No other factor influenced nodal status. In breast conservation patients without adjuvant radiation, 5% (1 of 20) had local recurrence versus 0% (0 of 13) of patients who received postoperative radiation. Ductal carcinoma in situ (DCIS) was associated with 52% of tubular cancers. Second breast cancers developed in 16% of cases. There was no difference in presentation or outcome for pure versus mixed tubular carcinoma. Overall mortality was 2%. Overall survival for patients with tubular carcinoma is quite good. Breast conservation treatment results in low rates of local recurrence for tubular carcinoma with or without the use of adjuvant radiation therapy. Pure tubular carcinomas had the same behavior and overall prognosis as mixed tubular carcinomas and should be classified together. Lymph node status did not influence disease-free or overall survival.

Large-needle core biopsy in atypical intraductal epithelial hyperplasia including immunohistochemical expression of high molecular weight cytokeratin: analysis of results of a single institution.

The diagnosis of atypical intraductal epithelial hyperplasia (AIDH) constitutes 6.3% of the breast core biopsies performed at our institution. Seventy-nine cases that were diagnosed as AIDH on core biopsy and went through excisional biopsy were included. Sixty-four biopsies were performed by an image-guided 11-gauge vacuum device, 11 under sonographic guidance using 14-gauge needles and 4 by a sonographically guided 11-gauge vacuum device. The histopathology of the core biopsies and the surgical excisions were reviewed. Immunohistochemistry was performed on the consecutive sections of core biopsy specimens using high molecular weight cytokeratin (HMW-CK) (DAKO-Cytokeratin, 34betaE12). At interpretation of the stain, intensity and percentage of positive cells were taken into account. The immunoprofiles of AIDH were categorized into four groups showing negative (i.e., no staining) or low-, moderate-, high-, and very high-intensity staining. Surgical excision of the 79 lesions revealed carcinoma in only 3 cases (4%)-two infiltrating carcinomas and one intraductal carcinoma-residual AIDH in 44 cases (56%), and epithelial hyperplasia or other benign lesions without atypia in 32 cases (40%). The HMW-CK stain was performed retrospectively on all of the core biopsies and 66 of them contained residual areas with AIDH for staining. Forty-nine (74%) were CK negative or stained with low intensity, but 17 cases (26%) had a moderate- to high-intensity stain. Our study showed a lower incidence of carcinoma on surgical excision following core biopsy for AIDH than other studies. The HMW-CK stain helped to characterize the nature of the intraductal proliferation and to confirm the presence of atypia, as has been previously reported, but frequently was inconclusive. The low incidence of carcinoma brings into question the need for surgical excision of all cases of AIDH diagnosed by core biopsy.

Precursor B-cell lymphoblastic lymphoma/leukemia presenting as osteoblastic bone lesions.

Lymphoblastic lymphoma is a neoplasm of precursors lymphoid cells morphologically indistinguishable from those of acute lymphoblastic leukemia. Approximately 10% to 20% of cases are of the precursor B-cell (P-BLL) phenotype. This type of lymphoma most often manifests in the skin and lymph nodes. In recent years more case reports of P-BLL presenting as lytic bone lesions have appeared in the literature. We describe an interesting case of P-BLL/leukemia that initially presented as an osteoblastic bone lesion and discuss the differential diagnosis from a pathologic-radiologic standpoint.