Tag Archives: Anatomic Pathology Selected Abstracts

April 2024—Fumarate hydratase-deficient renal cell carcinoma is a rare and distinct subtype of renal cancer caused by FH gene mutations. FH negativity and s-2-succinocysteine (2SC) positivity on IHC can be used to screen for FH-deficient renal cell carcinoma (RCC), but their sensitivity and specificity are imperfect. The expression of AKR1B10, an aldo-keto reductase that catalyzes cofactor-dependent oxidation-reduction reactions, in RCC is unclear. The authors compared AKR1B10, 2SC, and FH as diagnostic biomarkers for FH-deficient RCC. They included genetically confirmed FH-deficient RCCs (n=58), genetically confirmed TFE3 translocation RCCs (TFE3-tRCC; n=83), clear cell RCCs (n=188), chromophobe RCCs (n=128), and papillary RCCs (pRCC; n=97).

March 2024—Lung transplantation is the definitive therapy for end-stage pulmonary sarcoidosis. While several case reports have described recurrent sarcoidosis in allografts, the incidence and clinicopathologic characteristics remain unclear. The authors conducted a study in which they characterized the clinical and histopathologic features of recurrent sarcoidosis diagnosed in post-transplant lung surveillance transbronchial biopsies (TBBx). They identified 35 patients who underwent lung transplant for pulmonary sarcoidosis during the study period. Eighteen (51 percent) of the patients experienced recurrent sarcoidosis post-transplant—seven females and 11 males (mean age at recurrence, 51.6 years).

February 2024—The gold standard for prostate cancer diagnosis is the pathological examination of prostate biopsy tissue by light microscopy. The application of artificial intelligence (AI) to digitized whole slide images (WSIs) can aid pathologists in cancer diagnosis, but robust, diverse evidence in a simulated clinical setting is lacking. The authors conducted a study to compare the diagnostic accuracy of pathologists who read WSIs of prostatic biopsy specimens with and without AI assistance. Eighteen pathologists, two of whom were genitourinary subspecialists, evaluated 610 prostate needle core biopsy WSIs prepared at 218 institutions, with the option for deferral. Two evaluations were performed sequentially for each WSI: the first without assistance and the second, conducted immediately thereafter, aided by Paige Prostate (Paige, New York City).

January 2024—Diffuse parenchymal lung disease is a well-recognized complication of systemic connective tissue disease but rarely arises in patients with psoriasis or psoriatic arthritis, which are poorly understood. Therefore, the authors conducted a study to characterize diffuse parenchymal lung disease (DPLD) associated with psoriasis or psoriatic arthritis, with or without prior immunomodulation. Their pathology consultation files were searched for patients having psoriasis or psoriatic arthritis and DPLD. After excluding cases with active infection or smoking-related DPLD only, 44 patients (22 of whom were women; median age, 60 years; range, 23–81 years) were enrolled in the study. Clinical history and pathology slides were reviewed.

December 2023—Cytomegalovirus hepatitis in allograft livers is a significant infectious complication for which the histology historically has been described as overlapping that of acute cellular rejection, a diagnosis that compels a different treatment regimen. The authors conducted a study to update the clinicopathologic features of cytomegalovirus (CMV) hepatitis and explore its clinical and histologic relationship with acute cellular rejection (ACR). They performed a retrospective analysis of 26 patients, across four institutions, who were diagnosed with CMV hepatitis, assessing clinical, histologic, and IHC features. Patients were predominantly CMV donor positive/recipient negative (D+/R-; n=9 of 15) and received a diagnosis of CMV hepatitis at a mean age of 52 years (standard deviation [SD], 17 years) and at a mean interval of 184 days (SD, 165 days) from transplantation. Mean CMV viral load at diagnosis was 241,000 IU/mL (SD, 516 000 IU/mL), and liver biochemical enzymes were elevated (mean alanine aminotransferase, 212 U/L [SD, 180 U/L]; mean aspartate aminotransferase, 188 U/L [SD, 151 U/L]; and mean alkaline phosphatase, 222 U/L [SD, 153 U/L]).

November 2023—Claudin-4 is a sensitive and specific marker for carcinoma in effusion cytology. The authors examined the diagnostic use of claudin-4 versus MOC-31 and Ber-EP4 by comparing their sensitivity, specificity, positive predictive value, and negative predictive value in differentiating carcinoma from mesothelioma and benign/mesothelial hyperplasia in effusion specimens. They conducted a retrospective study on a cohort of 229 cytology specimens, including 211 effusion fluid and 18 fine-needle aspiration specimens. The cytologic categories included 134 carcinoma, 28 mesothelioma, 46 indefinite (suspicious and atypical), and 21 benign.

October 2023—Special AT-rich sequence-binding protein 2, or SATB2, induces local chromatin loops to facilitate transcription. SATB2 immunostaining is commonly used as a marker for colorectal adenocarcinoma and osteosarcoma. The authors conducted a study to better understand the prevalence and diagnostic value of SATB2 expression in cancer by analyzing a comprehensive set of human tumors. SATB2 expression was analyzed in 15,012 tissue samples from 120 tumor types and subtypes and 608 samples from 76 nonneoplastic tissue types using IHC in a tissue microarray format. SATB2 positivity was found in 89 of the 120 (74 percent) tumor types—59 of the 120 (49 percent) had at least one moderately positive tumor and 38 of the 120 (32 percent) had at least one strongly positive tumor.

September 2023—Understanding of the pathologic and molecular features of endometrial cancer has advanced measurably since the FIGO (International Federation of Gynecology and Obstetrics) staging system was updated in 2009. New treatments, results of clinical trials, and prognostic survival data that correlate with pathologic and surgical findings have been reported. Therefore, the FIGO Committee on Women’s Cancer determined that changes to the FIGO system were necessary. The goals of the revised staging system are to further clarify the diverse biologic nature of endometrial carcinomas with differing prognostic outcomes, better define the prognostic groups, and create substages that yield more appropriate surgical, radiation, and systemic therapies. The cancer committee developed a subcommittee on endometrial cancer staging in October 2021, of which the authors are members.

August 2023—Gastric foveolar-type adenoma is a rare benign neoplasm that occurs sporadically or presents in patients with familial adenomatous polyposis. The molecular features of foveolar-type adenoma (FA) and the relationship between sporadic and syndromic lesions remain unclear. The authors conducted a study in which they performed clinicopathological, immunohistochemical, and genetic analyses of 18 sporadic and 30 familial adenomatous polyposis (FAP)-associated FAs. The majority of sporadic and FAP-associated FAs were located in the upper or middle third of the stomach on a background of fundic gland mucosa. Most lesions were low grade, but three had a high-grade component.

July 2023—High-grade appendiceal mucinous neoplasm is a relatively recent term that describes a rare epithelial neoplasm of the appendix that demonstrates pushing-type invasion but high-grade cytologic atypia. Because it has been understudied, the authors conducted a multi-institutional retrospective study to describe the clinicopathologic features of high-grade appendiceal mucinous neoplasm (HAMN). They reviewed the clinical and histologic features of 35 HAMNs and the molecular features of eight of the cases. Patients were an average of 57 years old and most commonly presented with abdominal or pelvic pain. Histologically, 57 percent of the tumors showed widespread high-grade features.

June 2023—The authors conducted a study to examine whether quantitative digital pathology can derive valuable information from readily available and inexpensive H&E slides and thereby augment routine pathologic reporting of colorectal carcinoma. They applied a quantitative segmentation algorithm (QuantCRC) to 6,468 digitized H&E slides of colorectal carcinoma (CRC). Fifteen parameters from each image were recorded and tested for associations with clinicopathologic features and molecular alterations. A prognostic model was developed to predict recurrence-free survival using data from the internal cohort (n=1,928) and validated on an internal test (n=483) and external cohort (n=938). There were significant differences in QuantCRC according to stage, histologic subtype, grade, venous/lymphatic/perineural invasion, tumor budding, CD8 IHC, mismatch repair status, KRAS mutation, BRAF mutation, and CpG methylation.    

May 2023—Although criteria for malignancy have been established for glomus tumors of soft tissue, no accepted criteria exist for gastroesophageal glomus tumors, which are considered to behave unpredictably. Benign and aggressive gastroesophageal glomus tumors have been shown to harbor CARMN::NOTCH2 fusions, but genetic features that predict clinical behavior have not been identified. The authors conducted a study in which they evaluated 26 gastroesophageal glomus tumors to investigate histologic and genetic features that may predict malignancy. Seventeen of the 26 (65 percent) patients were male. The median age at presentation was 54.5 years (range, 16–81 years).  

April 2023—Kaposi sarcoma can pose diagnostic challenges in biopsy specimens. Multiple histologic variants of cutaneous Kaposi sarcoma (KS) have been described. However, the histomorphologic spectrum of gastrointestinal KS has not been systematically studied. The authors presented a large multi-institutional case series that comprehensively evaluated 46 cases of KS involving the GI tract and identified seven histomorphologic variants, some of which had not previously been described. Five of the variants—lymphangioma/lymphangiectatic like (n=17), mucosal hemorrhage/telangiectatic like (n=17), mucosal inflammation like (n=15), granulation tissue like (n=13), and mucosal prolapse like (n=4)—were inconspicuous but had unique morphologic patterns. These variants easily can be misdiagnosed or misinterpreted on routine examination if KS is not considered and if the IHC stain for human herpesvirus-8 is not utilized.  

March 2023—Prognostic stratification of patients with surgically resected invasive pulmonary adenocarcinoma must be improved. The authors conducted a study to evaluate the prognostic value of complex glandular patterns (CGPs) in patients with resected stage I through IV lung adenocarcinoma. The presence of CGPs as a minor to predominant component was tested for association with overall survival (n=676) and relapse-free survival (n=463) after surgery. CGPs were observed in 284 (42 percent) tumors. Cribriform and fused gland were the predominant patterns in 35 and 37 cases, respectively. The presence of a cribriform pattern was associated with worse relapse-free but not overall survival.  

February 2023—Atypical mitosis is considered a feature of malignancy, but its significance in breast cancer remains elusive. The authors conducted a study to assess the clinical value of atypical mitoses in breast cancer and explore their underlying molecular features. They quantified and correlated atypical and typical mitotic figures with clinicopathological variables in a large cohort of primary breast cancer tissue sections (n=846) using digitalized H&E whole slide images. They also used RNA sequencing data from The Cancer Genome Atlas (TCGA) breast cancer data set (n=1,032) to link atypical mitoses to the underlying genetic alterations and pathways.

January 2023—Radioembolization therapy uses yttrium-90-impregnated resin or glass microspheres to selectively target hepatic lesions via transarterial radioembolization. Occasional cases of gastrointestinal (GI) tract injury secondary to nontargeted delivery of microspheres have been reported, but large descriptive pathology series are lacking.

December 2022—Prostatic duct adenocarcinoma, which is characterized by pseudostratified columnar epithelium, has historically been considered invasive carcinoma, although it may have an intraductal component.

November 2022—Appendiceal mucinous neoplasms show a range of morphologic features and biological risk. At one end of the spectrum, high-grade adenocarcinomas are cytologically malignant and exhibit infiltrative invasion, lymph node metastases, and behavior similar to that of extra-appendiceal mucinous adenocarcinomas.

October 2022—Uterine carcinosarcoma is an aggressive malignancy with few treatment options. A recent clinical trial has shown an increase in progression-free survival in patients with human epidermal growth factor receptor 2 (HER2)-positive serous endometrial carcinomas treated with anti-HER2–targeted therapies.

September 2022—Hypergastrinemia states, such as achlorhydria from gastric mucosal atrophy or a gastrin-producing tumor, have been associated with the development of enterochromaffin-like cell hyperplasia and gastric neuroendocrine tumors.

August 2022—Mucocele-like lesion of the breast is an uncommon entity. Studies show low rates of upgrade from core needle biopsy to excision. The authors conducted a study to evaluate features associated with upgrade of cases of mucocele-like lesion of the breast (MLL) diagnosed on core needle biopsy.

July 2022—Helicobacter pylori-associated gastritis and autoimmune gastritis may coexist in a subset of patients, necessitating treatment for both disorders. The authors conducted a study to identify autoimmune gastritis in the background of H. pylori infection.

June 2022—Appendiceal orifice mucosae often appear inflamed endoscopically, even when other colonic segments appear normal. Histological findings in biopsy samples taken from endoscopically abnormal mucosae may simulate a variety of inflammatory colitides.

May 2022—Carcinoma with apocrine differentiation is an androgen receptor-positive subset of triple-negative breast carcinoma. In addition to carcinoma with apocrine differentiation, other androgen receptor-positive triple-negative breast carcinomas occur, albeit less frequently.

• Histological regression in melanoma: impact on SLN status and survival
• CERTAIN study results: use of adjunctive p16 IHC in cervical biopsies

March 2022—Invasive gallbladder carcinoma is preceded by two main types of precursor lesions—intracholecystic papillary-tubular neoplasms and biliary intraepithelial neoplasias. Invasive gallbladder carcinomas with an intracholecystic papillary-tubular neoplasm (ICPN) component have more favorable prognoses than those without an ICPN component.

• Use of subtyping to predict behavior of papillary thyroid microcarcinomas • Gastrointestinal pathology in samples from COVID-19–positive patients • Assessment of an artificial intelligence system for prostate cancer detection • Expression patterns for Bcl-2, EMA, β-catenin, E-cadherin, PAX8, and MIB-1 in thymomas • Analysis of intraoperative frozen section biopsy of uterine smooth muscle tumors

January 2022—Ki67, a nuclear proliferation-related protein, is used extensively in anatomic pathology but has not become a companion diagnostic or a standard-of-care biomarker because of analytic variability in assay protocols and interpretation.

December 2021—It is unclear whether HER2+ tumors expressing estrogen receptor and progesterone receptor—that is, triple-positive breast carcinomas—show unique morphologic and clinical features and response to neoadjuvant chemotherapy.

November 2021—Metastasis to the thyroid gland is a rare occurrence that may pose a diagnostic challenge. The authors reported on the clinicopathological features, immunoprofile, molecular alterations, and outcomes of 30 patients with thyroid metastases who were treated at Memorial Sloan Kettering Cancer Center from 2003 to 2019.

October 2021—Squamous cell carcinoma is the most common malignancy of the anal canal and is strongly associated with human papillomavirus (HPV) infection. Characteristic genomic alterations have been identified in anal squamous cell carcinoma (SqCC), but their clinical significance and correlation with HPV status, pathologic features, and immunohistochemical markers are not well established.

September 2021—Nivolumab is an immune checkpoint inhibitor approved for treating many types of cancer, including hepatocellular carcinoma (HCC). Liver injury is a known complication in patients treated with nivolumab for nonliver tumors. The morphologic changes to tumor and nontumor liver have not been well-characterized in HCC patients.

August 2021—Pseudocarcinomatous squamous hyperplasia within the bone is uncommon and closely mimics well-differentiated squamous cell carcinoma. It arises from cutaneous or mucosal surfaces and grows directly into the bone. The authors conducted a study in which they analyzed a series of 31 pseudocarcinomatous squamous hyperplasia (PSH) cases and discussed the clinicopathologic features that distinguished PSH from squamous cell carcinoma (SCC).

July 2021—Microscopic colitis is characterized by chronic watery diarrhea, endoscopically normal findings, and abnormal histology. The disorder is most prevalent in adults. Pediatric cases are rare and may vary in presentation.

June 2021—Two etiopathogenic types of vulvar squamous cell carcinoma have been described: human papillomavirus associated and HPV independent. HPV-associated vulvar squamous cell carcinoma (VSCC) develops from the precursor high-grade squamous intraepithelial lesions (HSILs).

May 2021—Secondary involvement of the uterine cervix by nongynecologic neoplasms is rare, accounting for less than two percent of metastases to the gynecologic tract. The authors conducted a study to analyze the clinicopathologic features of cervical involvement by nongynecologic malignancies.

April 2021—Intraductal biopsy is commonly used preoperatively to evaluate the etiology of biliary strictures. It can be challenging to interpret intraductal biopsies. The diagnosis is often hindered by interobserver disagreement.

March 2021—Prostatic-type differentiation in the lower female genital tract is rarely encountered and its causes and clinical associations are not well established. Reports have invariably described ectopic prostatic-type differentiation within the vagina as restricted to the lamina propria. The authors encountered a patient receiving testosterone for gender dysphoria whose vaginectomy specimen showed a prostatic glandular proliferation within the surface epithelium. To elucidate its potential association with androgen exposure, they sought similar lesions, resected during a 26-year period, from patients with exogenous or endogenous androgen excess. Thirteen cases, involving the vagina (n =12) and exocervix (n =1), were identified.

February 2021—SARS-CoV-2 primarily causes pulmonary injury, but it has been implicated in hepatic injury through the use of serum markers and histologic evaluation. The histologic pattern of injury has not been completely described, and studies quantifying viral load in the liver are lacking. The authors conducted a study in which they reported the clinical and histologic findings related to the liver in 40 patients who died of complications of COVID-19. For the study, they subjected a subset of liver tissue blocks to polymerase chain reaction (PCR) for viral RNA. Peak levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated, with a median ALT peak of 68 U/L (normal up to 46 U/L) and median AST peak of 102 U/L (normal up to 37 U/L). Macrovesicular steatosis was the most common finding, involving 30 (75 percent) patients.

January 2021—The authors conducted a review of postmortem pulmonary histopathologic findings of COVID-19 pneumonia in patients who had a spectrum of disease course that ranged from rapid demise to prolonged hospitalization. They analyzed histopathologic findings in postmortem lung tissue from eight patients who died from COVID-19 pneumonia. Immunohistochemistry and next-generation sequencing (NGS) were used to detect the virus. Diffuse alveolar damage (DAD) was seen in all cases with a spectrum of acute phase or organizing phase, or both. IHC with monoclonal antibodies against SARS-CoV-2 viral nucleoprotein and spike protein detected virus in areas of acute but not organizing DAD.

December 2020—It can be difficult to distinguish metastatic melanoma from melanocytic nevi in lymph nodes. Because diffuse IHC PRAME (preferentially expressed antigen in melanoma) expression is detected in the majority of primary and metastatic melanomas, but rarely in nevi, the authors conducted a study in which they hypothesized that PRAME could be a useful adjunct marker for the diagnosis of melanocytes in lymph nodes. They examined 45 nodal melanocytic deposits comprising 30 nodal nevi and 15 melanoma metastases. The latter were not straightforward from a diagnostic perspective because they coexisted with nodal nevi or were present in perinodal fibrous tissue. All nodal nevi were negative for PRAME and all melanoma metastases were diffusely positive for PRAME IHC.

November 2020—Neuroendocrine neoplasms range from well to poorly differentiated and indolent to highly aggressive. The site of origin in metastatic neuroendocrine neoplasms has therapeutic and prognostic implications. SATB2 is a transcriptional regulator involved in osteoblastic and neuronal differentiation and a sensitive and specific marker of colorectal epithelium. The authors conducted a study to evaluate the expression of SATB2 in neuroendocrine neoplasms from various primary sites and its utility as a marker for determining the site of origin of these neoplasms. SATB2 IHC was performed on 266 such neoplasms, including lung small cell carcinomas (n = 39) and carcinoids (n = 30), bladder (n = 21) and prostate (n = 31) small cell carcinomas, and gastrointestinal/pancreatic neuroendocrine neoplasms of various primary sites (n =145) consisting of well-differentiated neuroendocrine tumors (WDNET, n =124) and poorly differentiated neuroendocrine carcinomas (PDNEC, n = 21).

October 2020—Immune checkpoint inhibitors are frequently used to treat a variety of solid tumors. These drugs involve upregulation of cytotoxic T cells, which can lead to immune-related adverse events, including those involving the gastrointestinal tract. The authors conducted a study to characterize the histological features of immune checkpoint inhibitor therapy-associated gastritis. Gastric biopsies from patients on immune checkpoint inhibitor therapy who had clinical suspicion of drug-associated gastrointestinal injury were identified. The predominant histological pattern of injury, distribution of injury, degree of tissue eosinophilia, and prominence of apoptosis were recorded.

September 2020—Identifying patients who respond to immune checkpoint blockade is a significant challenge in oncology. PD-L1 expression by immunohistochemistry is the diagnostic gold standard for patient selection, but it does not capture all patients who may respond to immune checkpoint blockade (ICB). Recent gene-expression studies of high-grade serous ovarian carcinoma have defined an immunoreactive molecular subtype that shows a measurable favorable difference in patient survival compared with nonimmunoreactive subtypes, but no studies have demonstrated its impact on predicting response to ICB. As a step toward establishing the predictive value of gene-expression classifiers in ICB, the authors assessed the relationship between PD-L1 IHC and molecular subtypes of ovarian epithelial cancer. They analyzed 93 tissue specimens from patients with stages III and IV disease and compared PD-L1 IHC with gene expression by Agilent microarrays using The Cancer Genome Atlas-defined subtypes.

August 2020—The authors conducted a study in which they reviewed 354 cases of malignant diffuse mesothelioma in women from a database of 2,858 histologically confirmed cases. Pleural predominance was noted with 78 percent of pleural malignant mesotheliomas (MM) and 22 percent of peritoneal MM. The pleural tumors consisted of 72 percent epithelioid, 19 percent biphasic, and nine percent sarcomatoid variant. The peritoneal tumors consisted of 82 percent epithelioid, 13 percent biphasic, and five percent sarcomatoid. The immunohistochemical profile was typical of what is well accepted and previously described for MM.

July 2020—Smooth muscle tumors represent the second most common mural mesenchymal neaoplasm in the gastrointestinal tract, yet established criteria for prognostically assessing these tumors are lacking. The authors conducted a study on a large cohort of surgically resected intramural gastrointestinal smooth muscle tumors from 31 institutions to identify potential prognostic features. At each location, expert gastrointestinal or soft tissue pathologists, or both, assessed pathologic features. IHC confirmation was required.

June 2020—The authors conducted a study in which they independently evaluated the utility and prognostic value of tumor budding according to International Tumour Budding Consensus Conference (ITBCC) criteria in a large well-characterized European gastric cancer cohort. They assessed tumor budding according to the ITBCC criteria for 456 consecutive, surgically treated gastric cancers using the scoring system Bd0 (no buds), Bd1 (one to four buds), Bd2 (five to nine buds), and Bd3 (10 or more buds). Cases with tumor budding were divided into low-budding (Bd1/Bd2) and high-budding (Bd3) groups. The tumor budding score was analyzed in relation to clinicopathological parameters, overall survival, and tumor-specific survival. The authors found that 115 (25.2 percent) cases had no tumor budding, 104 (22.8 percent) had low tumor budding, and 237 (52 percent) had high tumor budding.

May 2020—Flat epithelial atypia is an alteration of terminal duct lobular units by a proliferation of ductal epithelium with low-grade atypia. No consensus exists regarding whether the diagnosis of flat epithelial atypia in core needle biopsy necessitates excision. The authors retrospectively identified all in-house core needle biopsies with flat epithelial atypia obtained at their institution between January 2012 and July 2018. They reviewed all core needle biopsy slides and assessed radiologic-pathologic concordance. An upgrade was defined as invasive carcinoma or ductal carcinoma in situ in the excision, or both. The excision slides of all upgraded cases were re-reviewed.

April 2020—Lymphocytic esophagitis is a well-known manifestation of Crohn disease among children but is not considered an immune-mediated mucositis in adults. The authors conducted a study for which they hypothesized that adult-onset lymphocyte-predominant esophagitis is also an immune-mediated inflammatory pattern, the nature of which has been masked by other conditions that feature esophageal lymphocytosis and occur in older adults. The intent of the study was to consolidate diagnostic criteria for lymphocyte-predominant esophagitis and determine its clinical significance.

March 2020—Conflicting data about the clinical significance of microscopic Crohn disease activity at resection margins have led to varying practice patterns for routine reporting by pathologists. The authors performed a multicenter retrospective cohort study of 101 consecutive Crohn disease bowel resections during a 10-year period to characterize the association between active disease at resection margins and postoperative Crohn disease recurrence and time to recurrence. Margin slides were reviewed, and Crohn disease activity at the margins was graded as none, mild, moderate, or severe. The authors used logistic regression and Cox regression analyses, respectively, to evaluate the association between microscopic Crohn disease activity at the margins and postoperative recurrence and time to recurrence.

DNAJB1-PRKACA fusions in fibrolamellar hepatocellular carcinoma

Distinct patterns of human liver regeneration following massive hepatic necrosis
January 2020—Massive hepatic necrosis is a rare and often fatal complication of various liver injuries. However, some patients survive by spontaneous hepatic regeneration. It is known that surviving hepatocytes or progenitor cells, or both, can participate in this process, but the mechanism of hepatic recovery is vague.

Evaluation of tumor quantitation as an aid in predicting biochemical recurrence in organ-confined prostate cancer
December 2019—In the eighth edition of the AJCC Cancer Staging Manual, all organ-confined disease is assigned pathologic stage T2, without subclassification. The authors investigated whether total tumor volume (TTV) or maximum tumor diameter (MTD) of the index lesion, or both, enhance the ability to predict biochemical recurrence in pT2 patients. They identified 1,657 patients using digital tumor maps and quantification of TTV/MTD who had pT2 disease on radical prostatectomy.

Angiosarcoma of the liver: clinicopathologic features and morphologic patterns
November 2019—Angiosarcoma is a rare malignant neoplasm of the liver for which morphologic patterns have not been systematically studied. To provide more comprehensive data on morphologic patterns, the authors reviewed angiosarcomas that had been diagnosed between 1996 and 2016 at a large medical referral center. The major growth patterns were classified as sinusoidal (nonmass forming) or mass forming.

Keratin 17: a sensitive and specific biomarker of urothelial neoplasia
October 2019—There is a clinical need to identify novel biomarkers to improve diagnostic accuracy for detecting urothelial tumors. The authors conducted a study to evaluate keratin 17 (K17), an oncoprotein that drives cell cycle progression in cancers of multiple anatomic sites, as a diagnostic biomarker of urothelial neoplasia in bladder biopsies and urine cytology specimens. The authors evaluated K17 expression using IHC in formalin-fixed, paraffin-embedded tissue specimens of nonpapillary invasive urothelial carcinoma (UC; classical histological cases), high-grade papillary UC (PUC-HG), low-grade papillary UC (PUC-LG), papillary urothelial neoplasia of low malignant potential (PUNLMP), and normal bladder mucosa.

Validation of 2016 ITBCC recommendations for tumor budding in stages I–IV colorectal cancer
September 2019—Tumor budding is a robust prognostic parameter in colorectal cancer and can be used as an additional factor to guide patient management. Although backed by large bodies of data, a standardized scoring method is essential for integrating tumor budding into reporting protocols.

July 2019—Although the majority of low-grade, early stage endometrial cancer patients have good survival rates with surgery alone, patients who recur tend to do poorly. Identifying patients at high risk of recurrence who would benefit from adjuvant treatment or more extensive surgical staging would improve individualized care for endometrial cancer patients.

June 2019—Markers for differentiating triple-negative breast cancer from TTF1-negative
lung adenocarcinoma. Triple-negative breast cancer patients have an increased risk of developing visceral metastases and other primary nonbreast cancers, particularly lung cancer. The differential diagnosis of triple-negative breast cancer (TNBC) metastases and primary cancers from other organs can be difficult due to lack of a TNBC standard immunoprofile.

May 2019—ALK-rearranged tumors in the STUMP subcategory of uterine tumors: Smooth muscle tumor of uncertain malignant potential is a rare diagnosis rendered when there is uncertainty concerning the biological potential of a smooth muscle tumor. The initial differential diagnosis is often broad, as tumors in this subgroup are morphologically heterogeneous. Recent data suggest that uterine inflammatory myofibroblastic tumors (IMTs) with anaplastic lymphoma kinase (ALK) rearrangement may be misclassified as smooth muscle tumor of uncertain malignant potential (STUMP), but the extent to which this occurs has not been examined.

April 2019—Frequent GNAQ and GNA14 mutations in hepatic small vessel neoplasm: April 2019—Hepatic small vessel neoplasm is a recently described infiltrative vascular neoplasm of the liver composed of small vessels. Although its infiltrative nature can mimic angiosarcoma, hepatic small vessel neoplasms (HSVNs) are thought to be benign or low-grade neoplasms because they lack cytologic atypia and increased proliferation.

March 2019—ALK expression in angiomatoid fibrous histiocytoma: a potential diagnostic pitfall: The authors recently encountered a case of primary pulmonary angiomatoid fibrous histiocytoma (AFH), which was initially misdiagnosed as inflammatory myofibroblastic tumor based in part on anaplastic lymphoma kinase expression by IHC. Prompted by this experience, they evaluated anaplastic lymphoma kinase (ALK) expression in 11 AFH, 15 inflammatory myofibroblastic tumors (IMT), and 11 follicular dendritic cell sarcomas using three antibody clones: D5F3, 5A4, and ALK1.

February 2019—Diagnostic algorithmic proposal based on IHC evaluation of invasive endocervical adenocarcinomas: The International Endocervical Adenocarcinoma Criteria and Classification was developed to separate endocervical adenocarcinomas into two main categories based on morphology: human papilloma virus-associated (HPVA) and nonhuman papilloma virus-associated adenocarcinomas.

January 2019—Distinguishing patients with double somatic mismatch-repair mutations from those with Lynch syndrome: Lynch syndrome is the most common form of hereditary colon cancer. Germline mutations in the mismatch-repair (MMR) genes MLH1, MSH2 (EPCAM), MSH6, and PMS2, followed by a second hit to the remaining allele, lead to cancer development.

December 2018—Applying deep convolutional neural networks to diagnostic breast biopsies: The breast stromal microenvironment is a pivotal factor in breast cancer development, growth, and metastases. Although pathologists often detect morphologic changes in stroma by light microscopy, visual classification of such changes is subjective and nonquantitative, limiting its diagnostic utility.

November 2018—HER2: a pan-cancer event highly enriched in AR-driven breast tumors: Approximately one in five breast cancers is driven by amplification and overexpression of the HER2 receptor kinase, and HER2 enriched is one of four major transcriptional subtypes of breast cancer. The authors conducted a study to understand the genomics of HER2 amplification independent of subtype, as well as the underlying drivers and biology of HER2-enriched (HER2E) tumors.

Analysis of ZC3H7B-BCOR high-grade endometrial stromal sarcomas October 2018—High-grade endometrial stromal sarcoma likely encompasses underrecognized tumors harboring genetic abnormalities besides YWHAE–NUTM2 fusion. Triggered by three initial endometrial stromal sarcomas with ZC3H7B–BCOR fusion characterized by high-grade morphology and aggressive clinical behavior, the authors investigated the clinicopathologic features of this genetic subset by expanding the analysis to 17 such tumors. All of the tumors occurred in women who were a median age of 54 (range, 28–71) years.

Thymoma: a clinicopathological correlation of surgical resection cases
September 2018—The authors presented 1,470 surgical resections for thymoma from the pathology files of 14 institutions in 11 countries with the purpose of determining and correlating a simplified histological classification of thymoma and pathological staging with clinical outcome.

Analysis of the surveillance of women diagnosed with atypical ductal hyperplasia on core needle biopsy
August 2018—A needle core biopsy diagnosis of atypical ductal hyperplasia is an indication for open biopsy. The launch of randomized clinical trials of active surveillance for low-risk ductal carcinoma in situ leads to the paradoxical situation of women with low-grade ductal carcinoma in situ being observed and those with atypical ductal hyperplasia having surgery.

Clinical and molecular analyses of neuroendocrine carcinomas of breast
July 2018—Clinical and molecular analyses of neuroendocrine carcinomas of breast: Neuroendocrine breast carcinomas represent a rare subtype of breast cancer. Their definition, prevalence, and prognosis remain controversial, as reported in the literature.

June 2018—Impact of pattern of invasion in invasive endocervical adenocarcinoma; Inflammatory myofibroblastic tumor of the uterus: an analysis of 13 cases.

May 2018—Outcomes related to use of hygroscopic sonographically detectable clips: The use of hygroscopic sonographically detectable clips (HSDCs) has dramatically increased in recent years, especially for breast cancer patients who undergo neoadjuvant chemotherapy. The authors conducted a study to define the appearance of HSDC sites in histopathological specimens and allow pathologists to recognize these sites and differentiate them from other lesions.

April 2018—Confirmation of ProMisE: a clinical classifier for endometrial cancer; Leiomyoma with bizarre nuclei: a morphological, IHC, and molecular analysis.

March 2018—Magee equation 3 for predicting response to chemotherapy in some breast tumors: Magee equations were derived as an inexpensive, rapid alternative to the Oncotype DX commercial assay. Magee equation 3 uses immunohistochemical and FISH data for estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 for its calculation: 24.30812+ERIHC×​(–.02177)+PRIHC×(−0.02884)+(0 for HER2 negative, 1.46495 for equivocal, 12.75525 for HER2 positive)+Ki-67×0.18649.

February 2018—ARTEMIS trial: quantifying pathological response to neoadjuvant chemotherapy: The Affordability and Real-World Antiplatelet Treatment Effectiveness after Myocardial Infarction Study, also known as the ARTEMIS trial, tested standard neoadjuvant chemotherapy with or without bevacizumab in the treatment of HER2-negative early breast cancer.

January 2018—Analysis of desmoplastic pattern at the tumor front in colorectal cancer subtypes: Although recent findings of cancer biology research indicate that prognostic power arises from genes expressed by stromal cells rather than epithelial cells, desmoplastic reaction has not been completely examined as a prognostic marker for colorectal cancer. The authors conducted a pathologic review of 821 stage II and III patients who underwent R0 resection for colorectal cancer at four independent institutions.

December 2017—Gene mutations in HPV-negative penile squamous cell carcinoma: The majority of penile squamous cell carcinomas are caused by transforming human papillomavirus infection. The etiology of HPV-negative cancers is unclear, but TP53 mutations have been implicated. Archival tissue from 108 invasive squamous cell carcinomas from a single pathology institution in a low-incidence area were analyzed for HPV-DNA and p16INK4A overexpression and for TP53 mutations by Ion Torrent next-generation sequencing.

November 2017—MCM2: an alternative to Ki-67 for measuring breast cancer cell proliferatio: Breast cancer is a heterogeneous disease comprised of a diversity of tumor subtypes that manifest themselves in a wide variety of clinical, pathological, and molecular features.

October 2017—Lymph node yield is an independent predictor of survival in rectal cancer: Lymph node yield is used as a marker of adequate oncological resection. The American Joint Committee on Cancer recommends at least 12 nodes to confirm node-negative disease for rectal cancer. However, it is not always possible to achieve a lymph node yield of 12, particularly in patients who have undergone neoadjuvant treatment.

Editors: Michael Cibull, MD, professor emeritus, University of Kentucky College of Medicine, Lexington; Rouzan Karabakhtsian, MD, PhD, associate professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.; and Rachel Stewart, DO, resident physician, Department of Pathology and Laboratory Medicine, University of Kentucky. Detection of HPV ...

August 2017—Analysis of microglandular adenosis and acinic cell carcinoma of the breast: Acinic cell carcinoma is an indolent form of invasive breast cancer, whereas microglandular adenosis has been shown to be a neoplastic proliferation. Both entities display a triple-negative phenotype and may give rise to, as well as display, somatic genomic alterations typical of high-grade triple-negative breast cancers. The authors compared previously published data on eight carcinoma-associated microglandular adenoses and eight acinic cell carcinomas subjected to massively parallel sequencing targeting all exons of 236 genes recurrently mutated in breast cancer or DNA repair related, or both.

July 2017—Potential quality indicators for lymph node staging of colon cancer: Evaluation of 12 or more lymph nodes is used as a quality indicator for adequacy of pathologic examination of colon cancer resections. The authors conducted a study to evaluate the utility of a focused lymph node search in the immediate vicinity of the tumor and a “second-look” protocol for improving lymph node staging in colon cancer.

June 2017—Fallopian tube involvement in uterine serous carcinomas: The authors investigated the frequency and histopathologic and immunohistochemical characteristics of tubal involvement in uterine serous carcinoma to clarify the relationship between serous tubal intraepithelial carcinoma (STIC) and uterine serous carcinoma. They prospectively collected and reviewed, for the presence of tubal involvement, cases of the latter with complete tubal examination.

May 2017—Value of Ki-67 proliferative index in WHO-classified pulmonary carcinoids; Chromosomal abnormalities and genetic changes in uterine smooth muscle tumors; Expression of divergent endodermal lineage markers in yolk sac tumors; Interobserver reproducibility of percent GP4 in prostatic adenocarcinoma on biopsies; MELF pattern invasion: a report of FIGO grade 1 endometrial endometrioid adenocarcinomas; Cost-effectiveness of identifying H. pylori  in gastric biopsies without ancillary stains

April 2017—Proposing prognostic thresholds for lymph node yield in oral cavity cancers: Prognostic lymph node yield thresholds have been identified and incorporated into treatment guidelines for multiple cancer sites, but not for oral cancer. The authors conducted a study to identify optimal thresholds in elective and therapeutic neck dissection for oral cavity cancers.

March 2017—An immunohistochemical algorithm for ovarian carcinoma typing: Five major histotypes of ovarian carcinoma exist. Diagnostic typing criteria have evolved over time, and past cohorts may be misclassified by current standards. The authors undertook an endeavor to reclassify the recently assembled Canadian Ovarian Experimental Unified Resource and Alberta Ovarian Tumor Type cohorts using immunohistochemical (IHC) biomarkers and to develop an IHC algorithm for ovarian carcinoma histotyping.

February 2017—Findings in hysterectomy specimens of women with Lynch syndrome; Percentages and architectural types of Gleason pattern 4 cancer in radical prostatectomy; PTEN loss and chromosome 8 alterations in Gleason grade 3 prostate cancer cores; Lymph node count from neck dissection predicts mortality in head and neck cancer; Assessing the adequacy of lymph node yield for papillary thyroid cancer; Addressing perceived versus actual agreement in breast pathology interpretation; Cost-effectiveness of Oncotype DX DCIS score for guiding treatment of DCIS

January 2017—Drawbacks of reflex ER and PR analysis of DCIS in breast needle core biopsies; Analysis of eosinophils and mast cells of gastrointestinal tract in healthy children; Classifying gastric cancer into molecular subgroups; Clinicopathologic significance of mismatch repair defects in endometrial cancer; Use of immunostains to distinguish hepatic adenoma from hepatocellular carcinoma; Prognostic effect of PD-L1 expression patterns in cervical cancers; Variation in pattern-based classification of invasive endocervical adenocarcinoma

December 2016—Reproducibility of NEPTUNE descriptor-based scoring system with various types of images: The multicenter Nephrotic Syndrome Study Network, or NEPTUNE, digital pathology scoring system uses a novel and comprehensive methodology to document pathologic features from whole-slide images, immunofluorescence, and ultrastructural digital images.

November 2016—Relevance of papillary growth patterns of pulmonary adenocarcinoma, HPV involvement in head and neck cancers: assessment of biomarkers, Distinctive immunoregulatory microenvironment of medullary carcinoma of the colon, Diagnostic challenges caused by endoscopic biopsy of colonic polyps, MicroRNA expression profiling and expression of miR-205 in inflammatory breast cancer

October 2016—Features of columnar-lined esophagus in gastroesophageal junction biopsies; Significance of Paneth cells in histologically unremarkable rectal mucosa; MicroRNA expression profile related to lymph node status in endometrial cancer; Plasma cells in melanoma: prognostic significance and possible role of IgA; Human epidermal growth factor receptor 2 testing in invasive breast cancer

September 2016—Digital image analysis versus manual biomarker assessment in breast cancer; Clinical and cost impact of EGFR and ALK testing in early stage NSCLC; Switch/sucrose nonfermenting complex protein expression in an aggressive endometrial cancer; Immune microenvironment of breast ductal carcinoma in situ; Adverse histological features in malignant colorectal polyps; Use of ancillary molecular analysis for diagnosis of soft tissue tumors

August 2016—Use of HSP70 and glutamine synthetase to diagnose hepatocellular carcinoma; Recurrence of benign and low-grade fibroepithelial neoplasms of the breast; Lobular neoplasia detected in MRI-guided core biopsy: a high risk for upgrade; Use of microsatellite instability, MLH1 methylation analysis, IHC to identify Lynch syndrome; Differential diagnosis of bladder versus colorectal adenocarcinoma; Enhanced expression of PD L1 in CIN and cervical cancers

July 2016—Evaluating perineural invasion as a prognostic factor in colorectal cancer; A morphological analysis of unusual features in apoplectic leiomyomas; Diagnosis of frozen section to guide resection strategy for lung adenocarcinoma; A finding of ovarian carcinoma histotype based on limited sampling

June 2016—Neuroendocrine differentiation in breast carcinoma; Comparison of bilateral versus unilateral multifocal papillary thyroid cancer

May 2016—Noninfectious aortitis of the ascending aorta: a histological and clinical correlation of cases; Stratifying HPV-induced cervical pathology using E4 with p16 or MCM; Limited resection versus lobectomy for older patients with early-stage lung cancer; L1CAM expression and its association with mutant p53 expression in endometrial cancer; Value of p16 staining for predicting outcome of LSIL/CIN1

April 2016—Comparison of methods for analyzing gene amplification in gastric cancers; Uterine smooth muscle tumor analysis by comparative genomic hybridization; Role of TAZ in aggressive types of endometrial cancer; Reclassification of resected lung carcinomas diagnosed as squamous cell carcinoma; Sequencing of cancer genes in ampullary carcinoma shows trends in histologic subtypes; Prognostic significance of the 2014 ISUP grading system for prostate cancer

March 2016—Reproducibility of residual cancer burden for assessing breast cancer after neoadjuvant chemotherapy: The residual cancer burden index was developed to quantify residual disease ranging from pathological complete response to extensive residual disease. The authors conducted a study to evaluate inter-pathologist reproducibility in the residual cancer burden index score and category and in their long-term prognostic utility.

February 2016—Subtype classification of lung adenocarcinoma in patients undergoing complete resection: The classification for invasive lung adenocarcinoma by the International Association for the Study of Lung Cancer, American Thoracic Society, European Respiratory Society, and World Health Organization is based on the predominant histologic pattern—lepidic, papillary, acinar, micropapillary, or solid—present in the tumor.

January 2016—Uterine leiomyosarcomas are rare malignant tumors with a poor prognosis, while leiomyomas are common benign tumors unrelated to their malignant counterparts. Diagnostic features commonly present in leiomyosarcoma include cytologic atypia, high mitotic index, and a sarcoma-specific geographic cell death designated as tumor cell necrosis (TCN).

December 2015—Reappraisal of etiologic field effect in cancer predisposition and progression: The term field effect, which is also known as field defect, field cancerization, and field carcinogenesis, has been used to describe a field of cellular and molecular alteration that predisposes to the development of neoplasms within that territory.

November 2015—Variation in reporting extraprostatic extension after radical prostatectomy: Extraprostatic extension of prostate cancer in radical prostatectomy specimens significantly affects patient management. The authors evaluated the degree of interobserver variation between uropathologists at a tertiary referral teaching hospital in assessing the extraprostatic extension of prostate cancer in radical prostatectomy specimens.

October 2015—CD117 expression in phyllodes tumors: correlation with adverse pathologic parameters. CD117 (c-Kit) is a type III receptor tyrosine kinase encoded by the KIT gene. Deregulation of expression and mutations in the gene are implicated in various tumors. Reports of CD117 expression in phyllodes tumors have generated controversy.

September 2015—Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy in select breast cancers: Modulation of immunologic interactions in cancer tissue is a promising therapeutic strategy. To investigate the immunogenicity of HER2-positive and triple-negative breast cancers, the authors evaluated tumor-infiltrating lymphocytes and immunologically relevant genes in the neoadjuvant GeparSixto trial.

August 2015—Quality of diagnostic staging in patients with bladder cancer: a process-outcomes link: Muscle sampling is often used as a surrogate for staging quality in patients with bladder cancer. The association of staging quality at diagnosis and survival was examined among patients with bladder cancer. The clinical records of all individuals within the Los Angeles Surveillance, Epidemiology, and End Results registry with an incident diagnosis of nonmuscle-invasive bladder cancer in 2004–2005 were reviewed.

July 2015—Expanding the morphologic spectrum of differentiated VIN by mapping p53 loss; Mitotic count by PHH3 immunohistochemical staining in pancreatic WDNETs; Comparison of prostate cancer markers in lymph node and distant metastases; Evaluation of a new grading system for laryngeal squamous intraepithelial lesions; Breast cancer assessment based on levels of estrogen receptor expression ...

June 2015—Safety and diagnostic accuracy of tumor biopsies in children with cancer; Napsin A as a specific marker for ovarian clear cell adenocarcinoma; Long-term follow-up of an active surveillance cohort of patients with prostate cancer; Primary sources of pelvic serous cancer in patients with endometrial intraepithelial carcinoma; Re-evaluating the role of sentinel lymph node biopsy in microinvasive breast carcinoma; Molecular analyses of six types of uterine smooth muscle tumors

Editors: Michael Cibull, MD, professor emeritus, University of Kentucky College of Medicine, Lexington; Rouzan Karabakhtsian, MD, attending pathologist, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.; and Rachel Stewart, DO, resident physician, Department of Pathology and Laboratory Medicine, University of Kentucky. Molecular detection of ...

April 2015—Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration; Histologic and immunohistochemical assessment of penile carcinomas in a North American population; Predictive value of IASLC/ATS/ERS classification of lung adenocarcinoma in tumor recurrence and patient survival; Histomorphology of Lynch syndrome-associated ovarian carcinomas with regard to a screening strategy

February 2015—Alteration of ARID1A gene, PI3K-Akt pathway, and ZNF217 gene in ovarian clear cell carcinoma: AT-rich interactive domain 1A (ARID1A) is a subunit of switch/sucrose nonfermentable (SWI/SNF) complex. Recently, alterations of the ARID1A gene, phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway, and zinc-finger protein 217 (ZNF217) gene have been identified as frequent molecular genetic changes in ovarian clear cell carcinoma.

January 2015—Are amended surgical pathology reports reaching the correct care provider? Amended reports need to follow patients to treating physicians to avoid erroneous management based on an original diagnosis. The authors undertook a study to determine if amended reports followed patients appropriately. They tracked amended reports with diagnostic changes and discrepancies between ordering and treating physicians.

December 2014—Value of autopsies in the era of high-tech medicine: Although the autopsy is still the gold standard for quality assessment of clinical diagnoses, autopsy rates have declined to less than 10 percent. The authors conducted a study to investigate the value of autopsies in the era of high-tech medicine by determining the frequency of discrepancies between clinical and autopsy diagnoses. The authors classified all adult autopsy cases (n=460) performed at the Symbiant Pathology Expert Centre in Holland, in 2007 and from 2012 to 2013, as having major or minor discrepancy or total concordance.

January 2013—Relationship between PAX2-null secretory cell outgrowths in the oviduct and pelvic serous cancer: With the exception of germ-line mutations in ovarian cancer susceptibility genes, genetic predictors for women destined for ovarian serous cancer cannot be identified in advance of malignancy. The authors recently showed that benign secretory cell outgrowths (SCOUTs) in the oviduct increase in frequency with concurrent serous cancer and typically lack PAX2 expression (PAX2-null).

November 2014—Final trial report of sentinel-node biopsy versus nodal observation in melanoma: Sentinel-node biopsy, a minimally invasive procedure for regional melanoma staging, was evaluated in a phase three trial. The authors evaluated outcomes in 2,001 patients with primary cutaneous melanomas who were randomly assigned to undergo wide excision and nodal observation, with lymphadenectomy for nodal relapse (observational group), or wide excision and sentinel-node biopsy, with immediate lymphadenectomy for nodal metastases detected on biopsy (biopsy group).

October 2014—Role of STAT6 immunohistochemistry in diagnosis of solitary fibrous tumors: Solitary fibrous tumor is an uncommon fibroblastic neoplasm. Although histologic characteristics and frequent CD34 expression allow for an accurate diagnosis in the majority of solitary fibrous tumor (SFT) cases, a wide histologic spectrum and occasional unexpected immunophenotype may pose diagnostic challenges. Molecular analyses have shown that almost all SFTs harbor a NAB2-STAT6 fusion gene, which is considered specific to this tumor type.

September 2014—Cytokeratin 17: an adjunctive marker of invasion in anal squamous neoplastic lesions: Diagnosing anal squamous cell carcinoma, which is often preceded by anal intraepithelial neoplasia, may be challenging in small biopsies. Cytokeratin 17 (CK17) is a basal/myoepithelial cell keratin induced in activated keratinocytes and associated with disease progression in squamous cell carcinoma (SCC) of the uterine cervix, esophagus, and oral cavity.

August 2014—GATA3: a multispecific but potentially useful marker in surgical pathology: The transcription factor GATA3 is important for differentiating breast epithelia, urothelia, and subsets of T lymphocytes. It has been suggested that it may be useful in evaluating carcinomas of mammary or urothelial origin or metastatic carcinomas, but its distribution in normal and neoplastic tissues is incompletely mapped. The authors conducted a study in which they examined normal developing and adult tissues and 2,040 epithelial and 460 mesenchymal or neuroectodermal neoplasms for GATA3 expression to explore its diagnostic value in surgical pathology.

July 2014—Assessing IHC biomarkers for basal-like breast cancer against a gene-expression profile gold standard: Gene-expression profiling of breast cancer delineates a particularly aggressive subtype referred to as basal-like. This subtype comprises approximately 15 percent of all breast cancers and afflicts younger women. It is refractory to endocrine and anti-HER2 therapies.

June 2014—Utility of triple antibody cocktail intraurothelial neoplasm-3 and AMACR in urothelial CIS and reactive urothelial atypia: Urothelial carcinoma in situ (CIS) is a prognostically and therapeutically significant lesion with considerable morphologic overlap with reactive conditions, especially in the setting of prior therapy. Various markers, including CK20, CD44s, and p53, have been used as an adjunct in making this distinction.

May 2014—Impact of operator techniques and specimen-preparation checklist on bone marrow assessment: Successful bone marrow assessment is essential to the diagnosis and staging of hematologic malignancies. The authors conducted a study to determine whether specific operator techniques or use of a specimen-preparation checklist, or both, could impact the quality of bone marrow assessment by reducing the frequency of obtaining nonspicular aspirates, small cores, and nondiagnostic samples.

April 2014—Clear cell papillary renal cell carcinoma: diagnosis and immunohistochemical profile: Clear cell papillary renal cell carcinoma is a recently recognized renal neoplasm composed of cells with clear cytoplasm lining cystic, tubular, and papillary structures. These tumors have immunohistochemical and genetic profiles distinct from clear cell renal cell carcinoma and papillary renal cell carcinoma. The authors studied morphologic and immunohistochemical features (cytokeratin 7 [CK7], carbonic anhydrase IX [CAIX], CD10, alpha-methylacyl-CoA racemase [AMACR], smooth muscle actin, desmin, and estrogen and progesterone receptors) in 55 tumors from 34 patients, eight of whom had end-stage renal disease.

March 2014—Use of morphological parameters of LN in stereotactic 11-gauge vacuum-assisted needle core biopsy: Management of lobular in situ neoplasia when diagnosed on core biopsy remains controversial. The authors conducted a study to investigate the association between morphological parameters of lobular in situ neoplasia (LN) on vacuum-assisted needle core biopsy (VANCB) and the presence of malignancy (ductal carcinoma in situ, pleomorphic lobular carcinoma in situ, or invasive carcinoma) at surgical excision. The study included 14 pathology departments in Italy.

February 2014—Early stage triple-negative breast cancer treated with mastectomy without adjuvant radiotherapy; Predicting recurrence after limited resection versus lobectomy for small lung adenocarcinoma; HER2 amplification in gastric cancer: a rare event restricted to intestinal phenotype; Gleason score undergrading on biopsy sample of prostate cancer; Fallopian tube intraluminal tumor spread from noninvasive precursor lesions; Factors that influence histopathological diagnosis of differentiated vulvar intraepithelial neoplasia; Impact of molecular analysis on final sarcoma diagnosis; Distinguishing primary bladder adenocarcinoma from secondary involvement by colorectal adenocarcinoma; Determining if close margins warrant postoperative adjuvant radiotherapy in oral squamous cell carcinoma; Three methodological approaches for defining basal-like lesions in triple-negative breast carcinoma

January 2014—Flat pattern of nephrogenic adenoma unveiled using PAX2 and PAX8 immunohistochemistry; Managing borderline atypical ductal hyperplasia/ductal carcinoma in situ on breast needle core biopsy; Classic lobular neoplasia on core biopsy: a clinical and radiopathologic study with followup excision biopsy; Intestinal-type endocervical adenocarcinoma in situ: a subset of AIS affecting older women; Oncotype DX recurrence score: use of pathology-generated equations from linear regression analysis; Neuroendocrine carcinoma of the stomach: characteristics and prognosis; Interobserver reproducibility in diagnosis of high-grade endometrial carcinoma; Features associated with metastatic potential in invasive adenocarcinomas of the lung

December 2013— Human papillomavirus-related carcinomas of the sinonasal tract; Localized and metastatic myxoid/round cell liposarcoma; Urothelial carcinoma with prominent squamous differentiation in neurogenic bladder: role of HPV infection; Atypical leiomyomas of the uterus: a clinicopathologic study of 51 cases; Clinicopathological significance of HER2/neu genetic heterogeneity in various breast carcinomas; EIN with secretory differentiation: features and underlying mechanisms; Glypican 3 and arginase in diagnosing scirrhous hepatocellular carcinoma

November 2013—Diagnostic and prognostic morphometric features in WHO 2003 invasive endometrial stromal tumors; Association of tumor staging with adverse clinical outcome in neuroendocrine tumors of appendix; Detection of HPV capsid proteins L1 and L2 in squamous intraepithelial lesions; Feasibility and safety of sequential research-related tumor core biopsies in clinical trials; Evaluation of breast amyloidosis finds AL type most prevalent; Outside case review of surgical pathology for referred patients: impact on patient care; Reporting trends for right-sided hyperplastic and sessile serrated polyps; Atypical leiomyomas of the uterus: a clinicopathologic study of 51 cases; Pathological diagnostic criterion of blood and lymphatic vessel invasion in colorectal cancer

October 2013—Acellular mucin in rectal cancer patients showing pathologic complete response to preoperative chemoradiotherapy; Association between p16 expression and human papillomavirus in urinary bladder squamous cell carcinoma; Immunohistochemical signature comprising PTEN, MYC, and Ki-67 and disease progression in prostate cancer; Preoperative BRAF(V600E) mutation screening: likelihood of altering initial surgery for indeterminate thyroid nodules; Claudin expression in high-grade invasive ductal carcinoma of the breast; Interobserver agreement in assessing lung cancer: H&E diagnostic reproducibility for non-small cell lung carcinoma

September 2013—Quantification of the Ki67 proliferative index in neuroendocrine tumors of the gastroenteropancreatic system; Clinicopathologic and immunohistochemical study of intrapulmonary SFTs; Papillary mucinous metaplasia of the endometrium as a precursor of endometrial mucinous adenocarcinoma; Expression of miRNAs and PTEN in endometrial specimens; Molecular investigation of lymph nodes in colon cancer patients using OSNA; Thymidylate synthase expression and molecular alterations in adenosquamous carcinoma of the lung; Microdensitometry of osteopontin as a prognostic biomarker in colorectal carcinoma tissue microarrays; Evaluation of pathological and molecular features in clinically aggressive dermatofibromas; Interobserver agreement in the reporting of colorectal polyp pathology by bowel cancer screening pathologists

August 2013—Endometrium as a primary site of origin of pelvic high-grade serous carcinoma in BRCA1 or BRCA2 mutation carriers; Criteria and pitfalls in diagnosis of lymphovascular invasion in prostatectomy specimens; An interobserver study of reproducibility in subtyping pulmonary adenocarcinomas; Value of PAX8, PAX2, claudin-4, and h-caldesmon in identifying peritoneal epithelioid mesotheliomas; Clinicopathologic study of cutaneous digital papillary adenocarcinoma;

July 2013—Intraoperative pathologic examination in the era of molecular testing for differentiated thyroid cancer: Diagnostic thyroidectomy is typically indicated for indeterminate thyroid cytology results. Traditionally, intraoperative pathologic examination (IOPE) helped guide the extent of initial surgery. Preoperative molecular testing of fine-needle aspiration cytology has emerged as another diagnostic adjunct, is highly specific for thyroid cancer, and can lead to appropriate initial total thyroidectomy.

June 2013—Prolonged cold ischemia time and ER immunohistochemistry in breast cancer: To aid detection of estrogen receptor expression in breast tumors, the American Society of Clinical Oncology and College of American Pathologists recommend that cold ischemia time be kept under one hour. However, data to address the upper threshold of cold ischemia time are limited.

May 2013—Pseudomyxoma peritonei originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The authors conducted a study to evaluate outcome and long-term survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an international registry study. A retrospective multi-institutional registry was established through the collaborative efforts of units affiliated with the Peritoneal Surface Oncology Group International.

April 2013—Preoperative diagnosis of benign thyroid nodules with indeterminate cytology: Approximately 15 percent to 30 percent of thyroid nodules evaluated by fine-needle aspiration are not clearly benign or malignant. Patients with cytologically indeterminate nodules are often referred for diagnostic surgery, though most of these nodules prove to be benign.

March 2013—Immunohistochemical assay versus Oncotype DX qRT-PCR assay for estrogen and progesterone receptors; accuracy and precision of endometrial intraepithelial neoplasia diagnosis; histologic patterns and molecular characteristics of lung adenocarcinoma; MicroRNA expression profiling as a diagnostic tool for thyroid cancer; inflammation and preneoplastic lesions in benign prostate as risk factors for prostate cancer; and reclassification of serous ovarian carcinoma using a two-tier system.

February 2013—BRCA1 and BRCA2 mutations, TP53 abnormalities, and immune cell infiltrates in ovarian carcinoma; Significance of loss of ARID1A/BAF250a expression in endometriosis; Relationship between pathologic complete response and prognosis after chemotherapy in breast cancer subtypes; Determining HER2 status on breast core-needle biopsies; Use of MiTF in differentiating cellular neurothekeoma from plexiform fibrohistiocytic tumor; A study of genetic heterogeneity in HER2/neu testing by FISH