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.

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.

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.

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.

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.

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.