Navigating HER2-Low Testing in Invasive Breast Cancer: Update Recommendations for Pathologists.

The article discusses the importance of accurately distinguishing HER2-low from HER2-negative breast cancer, as novel ADCs have demonstrated activity in a large population of patients with HER2-low-expressing BC. While current guidelines recommend a dichotomous classification of HER2 as either positive or negative, the emergence of the HER2-low concept calls for standardization of HER2 testing in breast cancer, using currently available assays to better discriminate HER2 levels. This review covers the evolution and latest updates of the ASCO/CAP guidelines relevant to this important biomarker in breast cancer, including still-evolving concepts such as HER2 low, HER2 heterogeneity, and HER2 evolution. Our group presents the latest Mexican recommendations for HER2 status evaluation in breast cancer, considering the ASCO/CAP guidelines and introducing the HER2-low concept. In the era of personalized medicine, accurate HER2 status assessment remains one of the most important biomarkers in breast cancer, and the commitment of Mexican pathologists to theragnostic biomarker quality is crucial for providing the most efficient care in oncology.

Molecular Mechanisms Involved in MAFLD in Cholecystectomized Patients: A Cohort Study.

Gallstone disease and metabolic dysfunction-associated fatty liver disease (MAFLD) share numerous common risk factors and progression determinants in that they both manifest as organ-specific consequences of metabolic dysfunction. Nevertheless, the precise molecular mechanisms underlying fibrosis development in cholecystectomized MAFLD patients remain inadequately defined. This study aimed to investigate the involvement of farnesoid X receptor 1 (FXR1) and fibroblast growth factor receptor 4 (FGFR4) in the progression of fibrosis in cholecystectomized MAFLD patients. A meticulously characterized cohort of 12 patients diagnosed with MAFLD, who had undergone liver biopsies during programmed cholecystectomies, participated in this study. All enrolled patients underwent a follow-up regimen at 1, 3, and 6 months post-cholecystectomy, during which metabolic biochemical markers were assessed, along with elastography, which served as indirect indicators of fibrosis. Additionally, the hepatic expression levels of FGFR4 and FXR1 were quantified using quantitative polymerase chain reaction (qPCR). Our findings revealed a robust correlation between hepatic FGFR4 expression and various histological features, including the steatosis degree (r = 0.779, p = 0.023), ballooning degeneration (r = 0.764, p = 0.027), interphase inflammation (r = 0.756, p = 0.030), and steatosis activity score (SAS) (r = 0.779, p = 0.023). Conversely, hepatic FXR1 expression did not exhibit any significant correlations with these histological features. In conclusion, our study highlights a substantial correlation between FGFR4 expression and histological liver damage, emphasizing its potential role in lipid and glucose metabolism. These findings suggest that FGFR4 may play a crucial role in the progression of fibrosis in cholecystectomized MAFLD patients. Further research is warranted to elucidate the exact mechanisms through which FGFR4 influences metabolic dysfunction and fibrosis in this patient population.

Mandibular Metastasis as the First Manifestation of Hepatocellular Carcinoma: A Case Report.

Metastatic malignancies of the oral cavity are rare lesions, accounting for only 1-4% of all oral malignancies, and can occur in the jaw bones, the oral soft tissues, or even both. Although hepatocellular carcinoma is the most common primary hepatic tumor, no more than 1% of the cases show oral involvement. When metastatic tumor involves the oral cavity, the most frequent site is the posterior angle of the mandible. Histologically, hence, immunohistochemical markers are used for diagnosis. Glypican-3 and HepPar1 are the markers that can be used to confirm the microscopic diagnosis of HCC. Very rarely, hepatocellular carcinoma (HCC) metastasizes to the oral cavity, and such cases have a poor prognosis due to delay in diagnosis. We present a 74-year-old male with a metastasis of HCC in the left mandibular body as the first manifestation. Histologic examination confirmed metastatic hepatocellular carcinoma in the oral mucosa with immunohistochemical (IHC) markers. A review of pertinent literature was performed. Given the rarity of the disease, treatment principles are based mainly on retrospective series and case reports. We report an exceptionally unusual presentation with few cases (<70) reported in the literature, thus representing a diagnostic challenge.

Expression of Programmed Death Ligand 1 in Breast Cancer in Mexican Women.

Background: Breast cancer is one of the most common malignant forms of neoplasia worldwide; programmed death protein 1 (PD-1), an inhibitory receptor of T lymphocytes, and its ligand programmed death ligand 1 (PD-L1), play an important role in the ability of tumor cells to evade the host's immune system. Methods: We conducted a descriptive, observational study using retrospective data and an open evaluation using immunohistochemistry to determine the general prevalence of PD-L1 expression in 63 women with breast cancer who underwent a modified radical mastectomy, or quadrantectomy, with axillary lymph node removal. Results: The prevalence of PD-L1 expression was 32% in patients with breast cancer treated with radical mastectomy. PD-L1 expression was higher in patients with large tumor size (19% for pT1, 37% for pT2, 50% for pT3, and 100% for pT4), metastasis in regional lymph nodes (25% for N0, 38% for N1, 75% for pN2, and 38% for pN3), and higher histological grade carcinoma (0% for grade 1, 23% for grade 2, and 50% for grade 3). Conclusions: These findings suggest that PD-L1 expression is heterogeneous in breast cancer tumors and that its expression varies highly in tumor regions over time. The evaluation of PD-L1 expression is significant, because of the therapeutical implications that could improve the outcomes and prognosis of these patients.

Identification of Hepatic Dendritic Cells in Liver Biopsies Showing Steatosis in Patients with Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Associated with Obesity.

BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) is now the term used for hepatic steatosis in patients who are overweight or obese, have type 2 diabetes mellitus (T2DM), or evidence of metabolic dysregulation. The prevalence of MAFLD among morbidly obese subjects is 65-93%. Hepatic dendritic cells (hDCs) are antigen-presenting cells that induce T cell-mediated immunity. MAFLD pathogenesis involves numerous immune cell-mediated inflammatory processes, while the particular role of hDCs is yet to be well defined. This study aimed to identify hDCs in liver biopsies from 128 patients with MAFLD associated with obesity. MATERIAL AND METHODS In this cross-sectional study, 128 liver biopsies from 128 patients with MAFLD (diagnosed as presence of hepatic steatosis, plus T2DM, metabolic dysregulation or overweight/obesity) were collected and assessed for CD11c⁺ immunoreactivity degree (CD11c as dendritic cell biomarker), through antigen retrieval, reaction with CD11c antibodies (primary), and marking with diaminobenzidine chromogen. RESULTS Among the 128 patients with MAFLD, 64 (50%) had MAFLD and fibrosis and 72 (56.2%) positively expressed hDCs (CD11c⁺). Among morbidly obese patients, 49 (64.5%) positively expressed hDCs (CD11c⁺) in liver tissue; from patients with obesity grade I- grade II (GI-II), 18 (54.5%) positively expressed hDCs (CD11c⁺) in liver tissue; and from non-obese patients with MAFLD, 5 (26.3%) positively expressed hDCs (CD11c⁺) in liver tissue. CONCLUSIONS hDC expression increases significantly in morbidly obese patients with MAFLD compared with non-obese patients, independent of the degree of fibrosis, suggesting the role of adaptive changes within hDCs in the perpetuation of inflammatory insults in chronic liver diseases.

Impact of the Discordance Between Scales of Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium in Patients' Prognosis With Metastatic Renal Cancer.

Background: In Mexico, about 30% of renal cancer patients are diagnosed in a metastatic state. Despite the recent advances in the treatment of cancer, metastatic renal cancer is still an incurable illness. Thus, identifying prognostic factors helps improve prognosis accuracy and survival prediction for patients. Methods: In this study, we retrospectively analyzed 26 patients with histological diagnosis of renal cell carcinoma, including clear cell and other subtypes in stage IV (metastatic), recurrent or unresectable disease. We performed a multivariate analysis of overall survival regarding the congruity between prognostic scales. Results: Our results showed a significant difference in favor of patients with congruity between scales for progression-free survival (18.9 vs. 3.1 months; P = 0.048) and a tendency towards better overall survival in patients with the congruity of both scales compared to the discordant patients (112 vs. 32 months; P = 0.99). Conclusion: This study highlights the discordance between Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium scales, which was associated with worse prognosis with a significant difference in progression-free survival but not in overall survival.

[An unusual association of malakoplakia and adenocarcinoma of the prostate]. / Asociación inusual de malacoplaquia y adenocarcinoma prostático.

Malakoplakia is a chronic inflammatory process caused by a lysosomal defect in bacterial digestion. Although rare, it occurs more frequently in the genitourinary tract and in patients with immune dysfunction. The bladder is the most commonly affected site, although cases have been reported in other organs, including the prostate gland. Clinically, this lesion can be confused with malignant tumours, both on physical examination and imagining techniques. This is particularly pronounced in the prostate, making the differential diagnosis challenging. Histologically, characteristic aggregates of histiocytes with basophilic intracytoplasmic inclusions composed of calcium and iron salts are found. We present a case diagnosed on transrectal biopsy as acinar adenocarcinoma with a Gleason 5 + 5 = 10 score. Prostatectomy revealed an unusual association of diffuse prostate malakoplakia and an area of acinar adenocarcinoma with a Gleason score of 3 + 4 = 7.

Impact of Testicular Germ Cell Tumor Laterality on Recurrence-Free Survival in the Mexican Population.

BACKGROUND: To date, the prognostic value of laterality for testicular germ cell tumors remains unknown. Herein, we describe this prognostic factor in the Mexican population. METHODS: A retrospective single-center study that included 37 patients with primary testicular germ cell tumors was conducted. Primary outcome was recurrence-free survival (RFS) at 2 years. Secondary outcomes were RFS by histology, progression-free survival by laterality, and 2-year overall survival. RESULTS: Thirty-seven patients were included, of which five showed relapses. By laterality, the 2-year RFS rate was 100% for left tumors and 77.3% for right tumors, with a trend toward statistical significance (P = 0.058). By histology, the RFS rate was higher for seminomas than non-seminomas (89% vs. 83%, respectively) without this difference being statistically significant. Progression-free survival was higher for right tumors than left tumors (91% vs. 80%, respectively) but without reaching statistical significance. The overall survival rate for the entire cohort was 94.5%. CONCLUSIONS: Our study shows that patients with primary germ cell tumors of the right testicle have a higher risk of recurrence than those with primary germ cell tumors of the left testicle, with a trend toward statistical significance.

Prevalence and Molecular Profile of Breast Carcinoma Using Immunohistochemistry Markers in Mexican Women.

BACKGROUND: In Mexico, breast cancer is the leading cause of death by malignant tumors in women aged 20 and older. The World Health Organization estimates that 69% of deaths caused by breast cancer occur in developing countries. Little is known about the prevalence of breast carcinoma in Mexico and its molecular subclassification. METHODS: This retrospective cross-sectional study included patients who underwent a mastectomy (single, radical or lumpectomy) or a breast tumor biopsy (core-needle or excisional) from January 2002 to December 2018. The primary purpose of the study was to determine the prevalence and molecular profile of breast in comprehensive cancer center in Mexico and compare our results with those published in the US. This study was approved by our scientific and bioethical committee. RESULTS: The final analysis included 379 patients. The youngest patient was 23 years old and the oldest patient was 89; the mean age at diagnosis was 54.63 years. Patients of 40 years old or younger accounted for 48 of the cases (12.66%) and those older than 40 accounted for 331 of the cases (87.33%). The molecular subclassification showed luminal A subtype in 139 cases (36.67%), luminal B subtype in 143 cases (37.73%), human epidermal growth factor receptor 2-positive carcinomas in 32 cases (8.44%) and triple-negative carcinomas in 65 cases (17.15%). Diabetes mellitus was present in 43 patients (11.34%), hypertension in 78 patients (20.58%), obesity in 82 patients (21.63%) and 66 patients reported being treated with exogenous hormone therapy (17.41%). CONCLUSIONS: Breast carcinoma occurs at an earlier age in Mexican women compared to women in the US. Hormone-positive tumors were found to be more prevalent in older patients, while high-grade tumors were more frequently identified in younger patients.

Myoepithelial Carcinoma Arising in a Plasmacytoid Myoepithelioma of the Parotid Gland Synchronized with Melanoma: A Case Report and Review of the Literature.

Myoepithelial carcinoma, also known as malignant myoepithelioma, is considered an extremely rare (0.45-1%) malignant salivary gland neoplasm. Approximately 100 cases have been reported in the English-language literature on myoepithelial carcinoma. The majority of the myoepitheliomas described in the literature have been benign, and the malignant counterpart is considered rare (<1%). Such a tumor may appear de novo or rarely develop from a preexisting pleomorphic adenoma (<20%), and in exceedingly rare cases (<0.5%), it has arisen from a benign myoepithelioma (i.e., plasmacytoid myoepithelioma). To our knowledge, no case of myoepithelial carcinoma of the parotid gland arising in a plasmacytoid myoepithelioma synchronized with melanoma has been reported to date. The treatment of myoepithelial carcinoma has been mainly surgical, including wide excision with free margins, with or without nodal dissection. The roles of chemotherapy and radiotherapy have not yet been established. We report a case of myoepithelial carcinoma of the parotid gland arising in a plasmacytoid myoepithelioma synchronized with melanoma in a 40-year-old woman. In our case, a complete response was achieved with surgery followed by adjuvant chemotherapy based on carboplatin and paclitaxel concurrent with radiotherapy.

Neuroendocrine Tumor of the Common Bile Duct: Case Report.

Carcinoma of the extrahepatic biliary tract accounts for <2% of all cancers. Neuroendocrine tumor of the extrahepatic bile duct is very rare, and there are <200 cases reported since 1959. The preoperative diagnosis is infrequent (5.12%). The definite diagnosis relies on postoperative pathology which utilized immunohistochemistry study on many biomarkers to diagnose the histological subtypes of neuroendocrine neoplasms, such as chromogranin A, synaptophysin, and neuron-specific enolase. When the primary tumor has no metastases, radical removal of the lesion appears as curative treatment. The treatment of the carcinoid syndrome or other functioning syndrome is the first priority. We report a case of a 12-year-old Mexican woman with neuroendocrine tumor of the extrahepatic bile duct (common bile duct neuroendocrine tumor) seen in our hospital. Resection of the common bile duct, cholecystectomy, end to side Roux-en-y hepaticojejunostomy, and portal lymphadenectomy was performed. A review of the pertinent literature was performed. Given the rarity of the disease, treatment principles are based mainly on retrospective series and case reports. We present the eighth case in adolescence in the literature.

Epithelial-Cadherin Expression Is Associated With Better Recurrence-Free and Overall Survival in Invasive Lobular Breast Cancer in Mexican Women.

BACKGROUND: There are different clinicopathological characteristics that are associated with the prognosis in patients with breast cancer. To date, the prognostic valor of for epithelial cadherin (E cadherin) expression in invasive lobular breast cancer remains unknown. METHODS: A retrospective single-center study that included 207 patients with primary invasive lobular breast cancer was conducted. The primary outcome was to report the correlation of the different clinical pathological characteristics including the expression of epithelial-cadherin (E-cadherin) in invasive lobular breast cancer in Mexican women with recurrence-free survival (RFS) and overall survival (OS). RESULTS: After 11 years of follow-up of patients with invasive lobular breast cancer, RFS was 89.4% and OS of 96.1%. The best prognosis in RFS was in patients with negative nodes 95.2% (P = 0.0001) and OS was 98.6-100% (P = 0.0001). Regarding tumor size, an RFS of 98.3% was observed in those measuring ≤ 2 cm (P = 0.0001) and OS of 99.2% (P = 0.0001). Negative Her2 was related to an RFS of 92.1% (P = 0.0001), and had better OS of 98.3% (P = 0.0001). Ki67 proliferation index ≤ 14% was associated with an RFS of 93.2% (P = 0.005). Negative lymph vascular invasion (LVI) increases the RFS of 91.8% (P = 0.032). The rate of positive expression of E-cadherin was associated with an increase in the RFS of 97.4%, with a mean of 128.6 ± 2.4 months (95% confidence interval (CI): 123.75 - 133.45 months) compared to the absence of expression E-cadherin: signal log ratio (SLR) 68.9%, a mean of 95 ± 6 months (95% CI: 83.28 - 106.88 months), P <0.001. When the OS was analyzed, the presence of E-cadherin expression increased the OS of 100% vs. 86.9% with the absence, P = 0.015. CONCLUSIONS: The prognostic impact of the different clinicopathological characteristics known worldwide was confirmed. Results of the analysis in the presented study indicate that positive expression of E-cadherin correlates with an improvement in OS and RFS in invasive lobular breast cancer in Mexican women.

Impact of the Type of Analgesic Therapy on Postsurgical Complications of Patients with Kidney Cancer Undergoing Nephrectomy.

BACKGROUND: The treatment of kidney cancer usually involves surgery, and in some cases systemic therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to control postsurgical pain in patients undergoing nephrectomy for renal cancer. Nevertheless, the association between these drugs and adverse postsurgical outcomes, including deterioration of renal function, is not fully established. METHODS: This retrospective cohort study included patients >18 years old with kidney cancer undergoing nephrectomy between January 2006 and January 2018. The primary endpoint was to determine the impact of postsurgical analgesic therapy (NSAIDs vs. acetaminophen) on renal function and postsurgical complications. This study was approved by our scientific and bioethical committee. RESULTS: One hundred patients were included in the final analysis. Clear-cell renal-cell carcinoma was the most frequent histologic subtype. Adequate acute pain control was accomplished in 91% of the patients during hospitalization. Twenty percent of the patients presented postsurgical complications. Bleeding-related complications were the most frequent (9%), followed by surgical-site infection (6%) and acute renal injury (6%). The administration of NSAIDs was not related to any postsurgical complication in comparison with the use of acetaminophen (21.3 vs. 17.9%, respectively). The length of hospital stay did not differ between patients treated with NSAIDs and those treated with acetaminophen (the average stay was 4 days for both groups, p = 0.32). CONCLUSION: The use of NSAIDs was not related to acute kidney injury, postsurgical complications, or prolonged hospital stay in patients with renal cancer undergoing nephrectomy.

Epidemiological Profile of Patients of Aged 65 Years and Over in a University Private Hospital.

OBJECTIVES: An increase in life expectancy is predicted for the general population and, by 2050, about one billion people will be older than 65 years. The Global Cancer Incidence, Mortality and Prevalence database estimates that 1.2 million people of this age will have cancer; this number represents 58% of new cases in the American population. This represents a challenge for diagnosis and treatment, given that some older people have multiple comorbidities and disabilities. MATERIALS AND METHODS: This was a retrospective descriptive study of 204 patients aged 65 years and over. All had a solid tumor that was diagnosed in a private hospital from January 2015 to December 2017. RESULTS: The median age was 72.2 years; the most frequent age group (48.5% of patients) was 65-75 years, and only a small percentage (4.4%) were aged > 85 years. The most common type of cancer was lung cancer (22.5%), followed by colorectal and urinary cancer. Most patients received cancer treatment after the disease diagnosis. CONCLUSION: There are no epidemiological studies of the older oncology population in Mexico. We believe it is necessary to perform larger studies to understand this population and to undertake actions to facilitate greater attention to patient diagnosis, treatment, and alleviation.

Risk of Pneumonitis with the Use of Different Immune Checkpoint Inhibitors in a Mexican Population.

PURPOSE: The incidence of pneumonitis reported in previous trials in patients with advanced cancer and use of programmed cell death protein 1 (PD-1) immunotherapy inhibitors was 2.7-3.6%. However, none of these trials included Mexican populations. METHODS: This was a retrospective analysis involving 87 patients with advanced cancer who received PD-1 inhibitors as part of their therapy. The primary outcome was the incidence of pneumonitis after using PD-1 inhibitors. The secondary outcomes were major risk factors and radiological patterns of pneumonitis. RESULTS: We found 13 cases of pneumonitis, giving an overall incidence of 15%; three of the cases were high-grade (grade 3). A ground-glass pattern was the major form found by chest computed tomography scans. We did not find any significant risk factor for pneumonitis. CONCLUSION: The incidence of pneumonitis secondary to treatment with PD-1 inhibitors in our Mexican population was 15%, which is 5 times higher than that found in other studies. No risk factor was identified for this increased incidence of drug-induced pneumonitis following the use of PD-1 inhibitors.

Spontaneous regression as a 'burned-out' non-seminomatous testicular germ cell tumor: a case report and literature review.

Testicular germ cell tumors (TGCTs) are the most frequent type of cancer in young adults. An exceptional event is the spontaneous regression (SR) of the primary tumor. Herein, we describe a burned-out non-seminomatous TGCT case and relevant literature review. A 34-year-old male presenting with low back pain was found to have a retroperitoneal mass upon urotomography. During workup, a heterogeneous testicular mass was evident, and its biopsy showed findings that support the diagnosis of spontaneous tumoral regression. The patient underwent unilateral orchiectomy and a chemotherapy protocol was later initiated, with 85% regression of the retroperitoneal metastatic mass. No progression of the primary tumor has been found. The etiology of SR across different cancer types appears to be associated with the host's immune response and an angiogenic disturbance of the tumor microenvironment. The burned-out phenomenon is a rare event that needs further research into its molecular sequencing.

Searching for the Culprit: Metastases from a Cancer of Unknown Primary.

We report a case of metastases from a cancer of unknown primary whose primary site could not be identified during the appropriate pretreatment evaluation. The patient was a 58-year-old woman with a history of passive smoking and with no history of cancer in the family. Her current condition started with asthenia, adynamia, and pallor, followed by palpitations. An abdominopelvic computed tomography (CT) scan was performed, showing multiple osteolytic lesions distributed in all bone structures and axillary adenopathy on the left side. As part of the approach and given the high suspicion of multiple myeloma, tests were performed. The results were negative for multiple myeloma. A PET-CT scan was performed and showed left axillary adenopathy. The breasts and other organs were not affected. Left axillary lymph node resection revealed breast primary metastatic pleomorphic lobular carcinoma. Due to the metastatic disease (caused by the primary breast cancer), it was decided to start chemotherapy.

Reproducibility of the EGFR immunohistochemistry scores for tumor samples from patients with advanced non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) is overexpressed in >60% of non-small cell lung cancer (NSCLC) cases. In combination with radiotherapy or chemotherapy, first-line treatments with antibodies against EGFR, including cetuximab and necitumumab, have demonstrated benefits by increasing overall survival (OS), particularly in patients who overexpress EGFR. The present study evaluated the interobserver agreement among three senior pathologists, who were blinded to the clinical outcomes and assessed tumor samples from 85 patients with NSCLC using the H-score method. EGFR immunohistochemistry was performed using a qualitative immunohistochemical kit. The reported (mean ± standard deviation) H-scores from each pathologist were 111±102, 127±103 and 128.53±104.03. The patients with average H-scores ≥1, ≥100, ≥200 and between 250-300 were 85.9, 54.1, 28.2 and 12.9, respectively. Patients who had an average H-score >100 had a shorter OS time compared with those with lower scores. Furthermore, patients with EGFR mutations who were treated with EGFR-tyrosine kinase inhibitors (TKIs) and had an average H-score >100 had a longer OS time compared with those with an average H-score <100. The interobserver concordance for the total H-scores were 0.982, 0.980 and 0.988, and for a positive H-score ≥200, the interobserver concordance was 0.773, 0.710 and 0.675, respectively. The determination of EGFR expression by the H-score method is highly reproducible among pathologists and is a prognostic factor associated with a poor OS in all patients. Additionally, the results of the present study suggest that patients with EGFR mutations that are treated with EGFR-TKIs and present with a high H-score have a longer OS time.

Histopathological transformation to small-cell lung carcinoma in non-small cell lung carcinoma tumors.

Lung cancer is the principal cause of cancer-related death worldwide. The use of targeted therapies, especially tyrosine kinase inhibitors (TKIs), in specific groups of patients has dramatically improved the prognosis of this disease, although inevitably some patients will develop resistance to these drugs during active treatment. The most common cancer-associated acquired mutation is the epidermal growth factor receptor (EGFR) Thr790Met (T790M) mutation. During active treatment with targeted therapies, histopathological transformation to small-cell lung carcinoma (SCLC) can occur in 3-15% of patients with non-small-cell lung carcinoma (NSCLC) tumors. By definition, SCLC is a high-grade tumor with specific histological and genetic characteristics. In the majority of cases, a good-quality hematoxylin and eosin (H&E) stain is enough to establish a diagnosis. Immunohistochemistry (IHC) is used to confirm the diagnosis and exclude other neoplasia such as sarcomatoid carcinomas, large-cell carcinoma, basaloid squamous-cell carcinoma, chronic inflammation, malignant melanoma, metastatic carcinoma, sarcoma, and lymphoma. A loss of the tumor-suppressor protein retinoblastoma 1 (RB1) is found in 100% of human SCLC tumors; therefore, it has an essential role in tumorigenesis and tumor development. Other genetic pathways probably involved in the histopathological transformation include neurogenic locus notch homolog (NOTCH) and achaete-scute homolog 1 (ASCL1). Histological transformation to SCLC can be suspected in NSCLC patients who clinically deteriorate during active treatment. Biopsy of any new lesion in this clinical setting is highly recommended to rule out a SCLC transformation. New studies are trying to assess this histological transformation by noninvasive measures such as measuring the concentration of serum neuron-specific enolase.

Cystadenomas of the liver and extrahepatic bile ducts: Morphologic and immunohistochemical characterization of the biliary and intestinal variants.

Cystadenomas of the liver and extrahepatic bile ducts (EHBD) are uncommon but distinctive neoplasms whose terminology and epithelial phenotype have been a source of controversy. We reviewed 20 cases, 16 arising in the liver and 4 in the EHBD. Eighteen patients were women, with a mean age of 36.5 years. Eighteen tumors were multiloculated and 2 were unilocular. The tumor size ranged from 4 to 29 cm (average, 11 cm). The cyst fluid in 13 tumors was described as serous, in 2 as clear, in 2 others as hemorrhagic, and in 1 as serous and mucinous. Only in 2 tumors was the fluid described as mucinous. In 18 cystadenomas, the predominant epithelial lining consisted of a single layer of cuboidal or low-columnar nondysplastic cells similar to those of the gallbladder or bile ducts. This epithelial lining was strongly positive for cytokeratins 7 and 19, and focally positive for MUC1. Only 2 cystadenomas showed predominant intestinal differentiation characterized by mature goblet cells and columnar absorptive cells. These cells expressed CDX2, MUC2, and cytokeratin 20. Admixed with the goblet and columnar cells, there were serotonin-containing cells and Paneth cells. These 2 tumors showed extensive areas of high-grade dysplasia and invasive adenocarcinoma with intestinal phenotype. A subepithelial ovarian-like stroma was present in all tumors. None of the patients died of the tumors. We believe that the term mucinous cystic tumor recommended by the World Health Organization for all cystadenomas of the liver and EHBD is a misnomer.