Crotalid Polyvalent F(ab)2 Antivenom Treatment in a Red-Tailed Hawk (Buteo jamaicensis).

Envenomation in avian species can result in death, with few cases of successful treatment described. A juvenile, wild-caught, intact female red-tailed hawk (Buteo jamaicensis) used in falconry was presented for emergency evaluation after being bitten by a Northern Pacific rattlesnake (Crotalus oreganus) approximately 2 hours before presentation. On presentation, the bird was quiet, alert, and responsive, with moderate swelling and discomfort of the digits on the right foot. Complete blood count (CBC) and plasma biochemistry abnormalities included a regenerative left shift, severe lymphopenia, and a moderate hypoproteinemia characterized by moderate hypoalbuminemia. Analgesic and antibiotic medications were administered during hospitalization. In addition, 5 mL of VenomVet was administered intravenously with crystalloid fluids over 60 minutes; no adverse effects were noted secondary to infusion. Improvement in the swelling was observed immediately after antivenom administration and nearly resolved within 12 hours. Complete resolution of digital swelling with no discomfort on palpation of that foot was observed 1 week after initial presentation. Blood collected at the 1 week reexamination was submitted for a CBC and plasma biochemistry panel. The results of the CBC revealed a reduced regenerative left shift, increased heterophil count, and a moderate monocytosis; the lymphopenia was resolved. A mild hypoalbuminemia still persisted. Ten months after presentation, the bird was reported to be doing well with no changes in function of the right foot and subsequently released from captivity.

LIQUID NITROGEN CRYOSURGERY FOR CUTANEOUS AND OCULAR NEOPLASMS IN KOI (CYPRINUS CARPIO) AND GOLDFISH (CARASSIUS AURATUS): EIGHT CASES (2018-2019).

Cryosurgery, also known as cryotherapy and cryoablation, is a promising surgical technique that employs highly localized freezing to destroy damaged and diseased tissue, including benign and malignant neoplasms. This procedure has been reported in the treatment of chromatophoromas, fibromas, and peripheral nerve sheath tumors in piscine patients. This study presents eight clinical cases of cryosurgery on cyprinid pet fish for a wide array of neoplastic masses, including chromatophoromas, squamous cell carcinoma, and sarcomas that were diagnosed by histopathology. Surgical excision of external masses, liquid nitrogen cryotherapy, injectable medications (meloxicam and danofloxacin), and topical medical-grade honey were applied to the patients after biopsy sampling. Five out of seven cutaneous cases and two out of three ocular cases had complete resolution without recurrence for at least three months posttreatment. Treatment was unsuccessful for two of the cutaneous cases in which the cutaneous masses were extremely invasive, resulting in severe ulceration and deep invasion into the coelomic cavity. One of the ocular cases involved a corneal mass that did not change in size and had no complications after treatments, suggesting that the treatment might be useful in limiting growth. The effectiveness of cryotherapy appears to correlate with the tumor type, as well as the stage and progression of tumor invasion.

Cyclin D1 immunohistochemical staining to separate benign from malignant mesothelial proliferations.

The separation of benign from malignant mesothelial proliferations is a morphologically difficult problem. Mutations/deletions of components of the Hippo pathway are frequent in malignant mesotheliomas, and one downstream effect of aberrant Hippo signaling is increased production of cyclin D1. We examined expression of cyclin D1 nuclear staining in two tissue microarrays containing 52 reactive epithelial mesothelial proliferations, 51 reactive spindle cell mesothelial proliferations, 54 epithelial mesotheliomas, and 22 sarcomatous/desmoplastic mesotheliomas. When present, cyclin D1 staining was always strong, hence the arrays were scored as 0, 1-25%, 26-50%, 51-75%, and 76-100% staining. Both arrays showed a similar pattern. Reactive epithelial proliferations generally showed no staining (42/52 cases) or 1-25% staining (10/52 cases) with no cases showing >25% staining. Overall for reactive epithelial proliferations the maximum staining was 14.8% and mean 1.1 ± 2.9%. For epithelial mesotheliomas 39/54 (72%) cases demonstrated >25% staining, with 8/54 in the 26-50% staining range, 9/54 in the 51-75% range, and 22/54 in the >75% range. Combinations of staining using cyclin D1 >50% plus BAP1 or MTAP loss in epithelial mesotheliomas produced about a 10% increase in sensitivity. Reactive spindle cell proliferations showed a broader range of staining with 27/51 in the 1-25% range, 5/51 in the 26-50% range, and 1/51 >50%. Eleven of 22 sarcomatous/desmoplastic mesotheliomas scored 50% or greater. We conclude that for epithelial mesothelial proliferations, the finding of >50% of tumor cells staining supports a diagnosis of epithelial mesothelioma with 100% specificity but only modest (57%) sensitivity.

MTAP immunohistochemistry is an accurate and reproducible surrogate for CDKN2A fluorescence in situ hybridization in diagnosis of malignant pleural mesothelioma.

Ancillary studies facilitate accurate diagnosis of morphologically challenging mesothelial proliferations. The current diagnostic algorithm proceeds from BAP1 immunohistochemistry to CDKN2A fluorescence in situ hybridization. While MTAP immunohistochemistry has recently shown promise as a surrogate for CDKN2A fluorescence in situ hybridization, it has been examined in only a few single-institution studies. Furthermore, there are no published reports on interobserver agreement or interlaboratory reproducibility for MTAP immunohistochemistry. We performed MTAP immunohistochemistry on 20 benign mesothelial lesions and 99 malignant mesotheliomas from five mesothelioma centers in four countries, and each MTAP stain was independently interpreted by four pathologists. CDKN2A fluorescence in situ hybridization data were available for a subset of cases, and a subset of cases was subjected in MTAP immunohistochemistry in multiple laboratories to assess interlaboratory reproducibility. Interobserver agreement in MTAP immunostain interpretation was excellent for all mesothelial lesions (kappa: 0.85) and for malignant mesothelioma cases only (kappa: 0.82). Interlaboratory reproducibility was also excellent (kappa values for paired protocols: 0.77-0.89). MTAP loss by immunohistochemistry was 78% sensitive and 96% specific for CDKN2A homozygous deletion. MTAP immunohistochemistry is a reliable surrogate for CDKN2A fluorescence in situ hybridization in diagnosis of malignant mesothelioma. Interobserver agreement is excellent for interpretation of MTAP staining, and protocols performed in different laboratories yield concordant MTAP staining results. Rare cases with immunohistochemical MTAP loss may retain normal CDKN2A copy number, and the MTAP staining results should be correlated with clinicopathologic findings and other ancillary studies.

Effects of Isoflurane Anesthesia on the Hematologic Values of Rehabilitated Wild Owls.

Isoflurane anesthesia is commonly used for owls when they are being rehabilitated to minimize stress during treatments and procedures, as well as to ensure caretaker safety. However, the effects of isoflurane anesthesia on the hematologic response of owls are not known. To investigate the effects of isoflurane anesthesia on the hematology of owls, 3 phases of investigation were performed on the subject animals: 1) single, short manual- versus single, short isoflurane-restraint episodes (n = 12; 38%); 2) a single, prolonged isoflurane episode (n = 10; 31%); and 3) serial, short isoflurane episodes (n = 10; 31%). All owls were classified as adult, and the sex for most individuals was unknown. Twelve owls (38%) were included in phase 1: 5 great horned owls (Bubo virginianus; 42%), 2 eastern screech owls (Megascops asio; 17%), and 5 barred owls (Strix varia; 42%). A separate cohort of 10 novel owls (31%) were selected for inclusion in both phases 2 and 3: 4 great horned owls (40%), 2 eastern screech owls (20%), 2 barred owls (20%), 1 barn owl (Tyto alba; 10%), and 1 snowy owl (Bubo scandiacus; 10%). For each anesthetic episode, blood was collected within 3 minutes of capture and in 15-minute intervals according to the duration of the procedure. Phase 2 had additional blood collections with the patient awake at 2 and 24 hours after time 0 blood collection, whereas phase 3 had an additional blood collection at 24 hours after time 0 blood collection. Hematologic analyses included packed cell volume, total solids, total white blood cell count, heterophil to lymphocyte ratio, and absolute heterophil, lymphocyte, monocyte, eosinophil, and basophil counts. Total white blood cell count decreased significantly during phase 1; packed cell volume decreased significantly during phases 2 and 3; total solids decreased significantly in phase 2; phase 2 demonstrated a lymphopenia with a concurrent decrease in the heterophil to lymphocyte ratio; and phase 3 demonstrated a heteropenia and significant changes in the eosinophil count. All hematologic changes noted in the study were within appropriate reference intervals for the owls but do suggest that there are physiologic consequences of restraining and anesthetizing these avian patients.

Tumor budding as a standardized parameter in gastrointestinal carcinomas: more than just the colon.

Tumor budding, defined as single cells or clusters of less than five cells, is thought to be a histomorphologic marker of an aggressive tumor behavior mimicking the embryologic epithelial-mesenchymal transition, and has been well established in the past two decades as a poor prognostic factor in colorectal carcinoma. Slow uptake in routine reporting of this important pathologic prognostic feature was in part due to differing methods of assessment of budding reported in the literature, but has recently been clarified at a consensus conference on tumor budding in colorectal carcinoma. Tumor budding is also increasingly being reported as a useful pathologic prognostic feature in other gastrointestinal carcinomas, including esophageal squamous cell carcinoma and adenocarcinoma, gastric intestinal-type adenocarcinoma, pancreatic ductal adenocarcinoma, and ampullary adenocarcinoma. In this review, we will summarize the studies on tumor budding in gastrointestinal carcinomas, with a focus on the methods of assessment used and the potential clinical applications of the findings.

Cutaneous GVHD is associated with the expansion of tissue-localized Th1 and not Th17 cells.

Studies in mice have shown that proinflammatory Th17 cells can cause acute graft-versus-host disease (aGVHD) related tissue damage; however, whether they play a role in human aGVHD remains unclear. In a prospective study, we measured the proportion of Th17 cells in the blood and skin of patients at the onset of aGVHD. We found no difference in the proportion or amount of IL-17 produced by T cells in the blood of patients with aGVHD (n = 20) compared with time-matched patients without GVHD (n = 14). Moreover, Th17 cells were not increased in the skin of patients with cutaneous aGVHD (n = 7) compared with healthy controls (n = 10). In contrast, we found significantly more interferon-γ-producing T cells in the skin of patients with aGVHD compared with controls. These data support the long-standing paradigm that tissue localized interferon-γ-producing cells are the perpetrators of aGVHD.

Cutting edge: Increased IL-17-secreting T cells in children with new-onset type 1 diabetes.

CD4(+)FOXP3(+) regulatory T cells are essential for immune tolerance, and murine studies suggest that their dysfunction can lead to type 1 diabetes (T1D). Human studies assessing regulatory T cell dysfunction in T1D have relied on analysis of FOXP3-expressing cells. Recently, distinct subsets of CD4(+)FOXP3(+) T cells with differing function were identified. Notably, CD45RA(-)CD25(int)FOXP3(low) T cells lack suppressive function and secrete the proinflammatory cytokine IL-17. Therefore, we evaluated whether the relative fractions of CD4(+)FOXP3(+) subsets are altered in new-onset T1D subjects. We report that children with new-onset T1D have an increased proportion of CD45RA(-)CD25(int)FOXP3(low) cells that are not suppressive and secrete significantly more IL-17 than other FOXP3(+) subsets. Moreover, these T1D subjects had a higher proportion of both CD4(+) and CD8(+) T cells that secrete IL-17. The bias toward IL-17-secreting T cells in T1D suggests a role for this proinflammatory cytokine in the pathogenesis of disease.

Tumour to tumour metastasis: case of a carotid body paraganglioma metastatic to a hepatocellular adenoma.

Tumour to tumour metastases are uncommon, and we report a case of carotid body paraganglioma metastatic to a hepatocellular adenoma. A 54-year-old man presented after a CT chest for chronic cough that incidentally identified two liver lesions in segment 3 and caudate. The imaging findings were suspicious for atypical haemangiomas versus hepatocellular adenoma. The segment 3 lesion was biopsied, demonstrating beta-catenin activated hepatocellular adenoma. He underwent partial hepatectomy with pathology showing the beta-catenin activated hepatocellular adenoma contained a central area of paraganglioma. On closer review, the patient revealed a carotid body paraganglioma with lymph node metastases requiring resection 24 years earlier. He subsequently underwent left hepatectomy including the resection bed and caudate, which confirmed the caudate lesion as metastatic paraganglioma. This case demonstrates how paraganglioma can metastasise to liver decades after initial resection and provide insight into the diagnostic workup for hepatocellular adenoma with neuroendocrine features.

Diagnosis and treatment of Candida glabrata proventriculitis in an eclectus parrot (Eclectus roratus).

CASE DESCRIPTION: An 8-year-old sexually intact female eclectus parrot (Eclectus roratus) with a 4-day history of hyporexia and lethargy and a 1-day history of tenesmus was examined. CLINICAL FINDINGS: Severe leukocytosis characterized by severe heterophilia and moderate monocytosis was present. Marked dilation of the proventriculus and ventriculus and ascites were identified by means of radiography, coelomic ultrasonography, and contrast-enhanced CT, with no clinically relevant motility noted on ultrasonography. Results of coelomic fluid analysis were consistent with pyogranulomatous effusion. Endoscopy of the upper gastrointestinal tract following proventricular and ventricular lavage showed a thick caseous plaque occupying 30% of the caudal proventricular mucosa. Abundant yeast organisms were evident during cytologic examination of a proventricular and ventricular wash sample, and fecal culture yielded Candida glabrata. TREATMENT AND OUTCOME: The bird was treated with SC fluids, assisted feedings, nystatin, fluconazole, amoxicillin-clavulanic acid, enrofloxacin, gastroprotectants, maropitant, and analgesics and slowly improved during hospitalization. A marked decrease in proventricular dilation was evident on serial radiographs obtained over a 12-month period. One year after diagnosis, the bird was presented with a 1-week history of hyporexia and lethargy, and fecal culture grew C glabrata. Antifungal treatment was resumed for 3 months. The bird had no clinical signs of infection 16 months after this recurrence, and subsequent fecal cultures were negative for fungal growth. CLINICAL RELEVANCE: Findings illustrate the importance of upper gastrointestinal endoscopy in diagnosing proventricular and ventricular dilation in birds and emphasize the need for long-term antifungal treatment and monitoring in birds with fungal infections.

Usefulness of methylthioadenosine phosphorylase and BRCA-associated protein 1 immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens.

BACKGROUND: The separation of benign from malignant mesothelial proliferations on effusion cytology can be difficult. Loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry is an established marker of malignancy in mesothelial proliferations, but to the authors' knowledge largely has been applied only to biopsies. The current study was conducted to determine the usefulness of MTAP immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens. METHODS: A total of 21 effusion cytology cases of malignant mesothelioma were stained for MTAP and BRCA-associated protein 1 (BAP1), with 15 reactive mesothelial cytology cases used as a control. Fourteen cases had a paired surgical specimen for comparison, and 7 cases were run for CDKN2A deletion by fluorescence in situ hybridization. RESULTS: Complete loss of MTAP cytoplasmic staining was noted in 7 of 21 effusion samples (33%), and no loss was observed in 11 effusion samples (52%); 11 of these cases had a matching surgical specimen and all 11 specimens demonstrated the same MTAP pattern. Partial loss was observed in 3 effusion specimens (80%, 40%, and 40% intact staining, respectively), but in all 3 the surgical specimen demonstrated 100% staining. None of the 15 reactive mesothelial cytology specimens demonstrated MTAP cytoplasmic loss. CDKN2A FISH demonstrated concordance in 5 of 7 cases (71%). MTAP immunohistochemistry had a sensitivity of 33% and a specificity of 100% for this differential diagnosis. CONCLUSIONS: MTAP staining demonstrated generally good concordance between the cytologic and surgical specimens and appears to be useful in the diagnosis of mesothelioma on effusion specimens. Complete loss of MTAP is a reliable marker of malignancy, but the significance of partial loss of MTAP staining is unclear.

Re-examining the 1-mm margin and submucosal depth of invasion: a review of 216 malignant colorectal polyps.

Malignant colorectal polyps have a risk of lymph node metastases between 9 and 24%, but patients who are negative for certain histologic poor prognostic factors have the potential to be treated with polypectomy alone. Retrospective cohort of 216 malignant polyps from 213 patients identified through the British Columbia Colon Screening Program. Complete pathologic reporting (reporting of tumor grade, lymphovascular invasion, margin status, and tumor budding) was present in only 43% of patients. Sixty-one patients had no poor prognostic factors on polypectomy, and 23 (37%) of those underwent surgery. A positive margin cutoff of tumor at cautery showed significantly increased rates of lymph node metastases (p = 0.04) compared to a margin of greater than 0 mm, and polyps with a margin of greater than 0 mm had no risk of residual carcinoma. A submucosal depth of ≥ 2000 µm had an increased rate of lymph node metastases compared to < 2000 µm (p = 0.01). Malignant polyps with either tumor at cautery or a submucosal depth of ≥ 2000 µm, compared to polyps without these risk factors, had a relative risk for lymph node metastases of 16.3. Adoption of submucosal depth and refinement of the cutoffs for positive margin and submucosal depth have the potential to identify high-risk patients and reduce the number of surgeries required in patients with malignant polyps, a group that continues to grow significantly in part due to the introduction of colon screening programs.

Pharmacokinetics of amantadine after oral administration of single and multiple doses to orange-winged Amazon parrots (Amazona amazonica).

OBJECTIVE: To determine the pharmacokinetics of amantadine after oral administration of single and multiple doses to orange-winged Amazon parrots (Amazona amazonica). ANIMALS: 12 adult orange-winged Amazon parrots (6 males and 6 females). PROCEDURES: A single dose of amantadine was orally administered to 6 birds at 5 mg/kg (n = 2), 10 mg/kg (2), and 20 mg/kg (2) in a preliminary trial. On the basis of the results, a single dose of amantadine (10 mg/kg, PO) was administered to 6 other birds. Two months later, multiple doses of amantadine (5 mg/kg, PO, q 24 h for 7 days) were administered to 8 birds. Heart rate, respiratory rate, behavior, and urofeces were monitored. Plasma concentrations of amantadine were measured via tandem liquid chromatography-mass spectrometry. Pharmacokinetic parameter estimates were determined via noncompartmental analysis. RESULTS: Mean ± SD maximum plasma concentration, time to maximum plasma concentration, half-life, and area under the concentration-versus-time curve from the last dose to infinity were 1,174 ± 186 ng/mL, 3.8 ± 1.8 hours, 23.2 ± 2.9 hours, and 38.6 ± 7.4 µg·h/mL, respectively, after a single dose and 1,185 ± 270 ng/mL, 3.0 ± 2.4 hours, 21.5 ± 5.3 hours, and 26.3 ± 5.7 µg·h/mL, respectively, at steady state after multiple doses. No adverse effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Once-daily oral administration of amantadine at 5 mg/kg to orange-winged Amazon parrots maintained plasma concentrations above those considered to be therapeutic in dogs. Further studies evaluating safety and efficacy of amantadine in orange-winged Amazon parrots are warranted.

Unusual Pathologic Brain Changes Associated with Zinc Toxicosis in a Blue-Fronted Amazon Parrot (Amazona aestiva).

An adult blue-fronted Amazon parrot (Amazona aestiva) was presented for a 6-wk history of ataxia and weight loss. Complete blood count, plasma chemistry panel, bile acids, and radiographic imaging were considered normal or unremarkable. The patient was hospitalized and supported with subcutaneous fluids, vitamin B complex, meloxicam, enrofloxacin, gavage feeding, and fenbendazole. While hospitalized, the ataxia significantly improved, and the bird began eating on its own and gaining weight. The bird was discharged from the hospital and prescribed enrofloxacin, meloxicam, and fenbendazole to be administered by the owner with recommendations for routine follow-up care. Medications were discontinued before emergent representation; at the time of reevaluation, the patient's condition had deteriorated severely. Given the poor prognosis, the owners elected for euthanasia. No gross abnormalities were noted on postmortem examination. Liver tissue zinc levels measured 125 ppm; normal limit is less than or equal to 25 ppm. Histopathologic changes to the brain were consistent with severe zinc toxicosis demonstrated by vasculopathy of the cerebral arteries and arterioles with multifocal areas of hemorrhage and astrocyte swelling. These findings have been reported in humans and other mammals but not birds. Although the source of this bird's heavy metal exposure is unknown, the high tissue zinc concentrations imply chronic exposure. This case presentation and unusual pathologic findings will be beneficial to the further understanding of avian zinc toxicosis.

Investigation of factors associated with spontaneous preterm birth in pregnant women living with HIV.

OBJECTIVE: To investigate factors contributing to preterm birth (PTB), including cART use and clinical and social determinants of health, in women living with HIV (WLWH) from British Columbia, Canada. DESIGN: Retrospective observational cohort. METHODS: We investigated the effect of cART use and other clinical and demographic factors on spontaneous PTB (sPTB) rates (<37 weeks gestational age) among 631 singleton pregnancies between 1997 and 2018. Exposure to cART was modelled in comparison to no exposure, exposure in the first trimester, and between regimens. Differences in sPTB risk were estimated using time-dependent Cox's proportional hazards models. RESULTS: Overall, the sPTB rate was 16%. Cumulative cART use was associated with lower risk of PTB (Wald test P = 0.02; hazard ratio = 0.98, 95% CI = 0.96-0.99) and specific cART regimens were not associated with increased risk of sPTB. Exposure in the first trimester was not associated with sPTB and for each week of cART exposure, the risk of sPTB decreased by 2%. In a multivariable model, HIV viral load and substance use remained associated with risk of sPTB, but not cART exposure. CONCLUSION: The sPTB rate among pregnant WLWH was more than three times higher than in the general population. However, sPTB was not related specifically to use of cART; in fact, cART appeared to reduce the risk of sPTB. Uncontrolled HIV replication and substance use were associated with increased risk of sPTB among pregnant WLWH. This emphasizes the important role of prenatal care, access to cART, and smoking cessation and harm reduction to reduce the risk of sPTB in WLWH.

Utility of Methylthioadenosine Phosphorylase Compared With BAP1 Immunohistochemistry, and CDKN2A and NF2 Fluorescence In Situ Hybridization in Separating Reactive Mesothelial Proliferations From Epithelioid Malignant Mesotheliomas.

CONTEXT.­: The separation of reactive from malignant mesothelial proliferations is often a difficult morphologic problem. There is contradictory information in the literature on whether methylthioadenosine phosphorylase (MTAP) immunohistochemistry can be used for this purpose. OBJECTIVE.­: To determine the utility of MTAP immunohistochemistry in distinguishing reactive from malignant mesothelial proliferations. DESIGN.­: We stained a tissue microarray containing 20 epithelioid malignant mesotheliomas and 17 reactive mesothelial proliferations. For the mesotheliomas, comparisons were made between MTAP staining and BRCA-associated nuclear protein 1 (BAP1) immunohistochemistry, cyclin-dependent kinase inhibitor 2A ( CDKN2A) fluorescence in situ hybridization, and neurofibromin 2 ( NF2) fluorescence in situ hybridization, which are established techniques for making this separation. RESULTS.­: Loss of MTAP was seen in 0 of 17 reactive mesothelial proliferations and 13/20 (65%) malignant mesotheliomas. Almost all cases with loss showed loss in 100% of mesothelial cells. Background inflammatory and stromal cells served as a positive internal control. CDKN2A fluorescence in situ hybridization on the mesotheliomas showed concordance with MTAP staining in 14 of 17 evaluable cases. BAP1 immunohistochemistry showed loss of nuclear staining in 11 of 20 mesotheliomas (55%). No cases showed loss of NF2. A total of 18 of 20 mesotheliomas (90%) showed loss of either MTAP or BAP1. CONCLUSIONS.­: In the context of a mesothelial proliferation, loss of MTAP staining is 100% specific for malignant mesothelioma. In this study the combination of MTAP and BAP1 immunohistochemical staining allowed separation of reactive from epithelial malignant mesothelial proliferations in 90% of cases.

SATB2 as an Immunohistochemical Marker for Colorectal Adenocarcinoma: A Concise Review of Benefits and Pitfalls.

SATB2 is part of the family of matrix attachment region-binding transcription factors, and has developmental roles in craniofacial, neural, and osteoblastic differentiation. Recently, SATB2 has been shown to be highly expressed in the epithelium of the lower gastrointestinal tract, with a relatively narrow expression profile in malignancies, including colorectal/appendiceal adenocarcinomas, tumors of osteoblastic differentiation, and renal/urothelial carcinomas. SATB2 has gained interest as a relatively specific marker of colorectal differentiation, with potential applications including determining origin of adenocarcinomas of unknown primary and distinguishing primary ovarian mucinous adenocarcinomas from colorectal metastases. Here, we briefly review the biology, expression profile, and potential histologic applications of SATB2.

GATA3 Immunohistochemistry for Distinguishing Sarcomatoid and Desmoplastic Mesothelioma From Sarcomatoid Carcinoma of the Lung.

The separation of sarcomatoid and desmoplastic malignant mesotheliomas from sarcomatoid carcinomas of the lung metastatic to the pleura may be difficult, since both types of tumor can be morphologically similar and are frequently positive only for pan-keratin. GATA binding protein 3 (GATA3) is most commonly used as an immunohistochemical marker of breast and urothelial carcinoma, but is also known to stain other types of tumors including some mesotheliomas. In this study we asked whether GATA3 stains could be used to distinguish sarcomatoid/desmoplastic malignant mesotheliomas (N=19) from sarcomatoid carcinomas of the lung (N=13). Tumor staining was scored for diffuseness and intensity, with a maximum possible score of 6. All 19 sarcomatoid/desmoplastic malignant mesotheliomas examined showed strong diffuse staining for GATA3 (no case scored <3, mean score±SD for all 19 cases 5.4±0.9), whereas only 2 of 13 sarcomatoid carcinomas of the lung stained positively for GATA3 and the staining was weak and patchy (score 2 for each case, mean±SD for all 13 cases 0.4±0.8). There was no correlation between the intensity and diffuseness of GATA-3 staining and staining for traditional mesothelioma markers. Overall, any positive staining for GATA3 was 100% sensitive and 85% specific for sarcomatoid/desmoplastic mesothelioma. We conclude that strong diffuse staining for GATA3 favors a diagnosis of sarcomatoid/desmoplastic malignant mesothelioma over metastatic sarcomatoid carcinoma of the lung; conversely, complete absence of GATA-3 staining is evidence against a diagnosis of sarcomatoid/desmoplastic malignant mesothelioma.