The American journal of surgical pathology
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Am. J. Surg. Pathol. · May 2010
KRAS mutations in traditional serrated adenomas from Korea herald an aggressive phenotype.
The pathogenesis and risk of malignancy of traditional serrated adenomas (TSAs) are unclear. In North America, TSAs are relatively uncommon, occur mainly in the left colon, and in some studies, have not been shown to have a strong association with hyperplastic polyp (HPP) or sessile polyp adenoma (SSA) precursor lesions. In the Far East, and particularly in Korea, TSAs are more common and occur both in the left and right colon. ⋯ Our results suggest that up to one-third of TSAs show a histologically identifiable nondysplastic HPP or SSA precursor lesion, particularly in lesions from the right colon. The development of KRAS mutations and methylation of MGMT may herald the onset of an aggressive phenotype in the neoplastic progression of TSAs and also suggests that a fusion between the serrated pathway of carcinogenesis and the chromosomal instability pathway may occur in some TSAs. Further studies are needed to determine the natural history and risk of malignancy of TSAs, specifically related to the anatomic site of development.
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Am. J. Surg. Pathol. · May 2010
Renal epithelioid angiomyolipoma with atypia: a series of 40 cases with emphasis on clinicopathologic prognostic indicators of malignancy.
As epithelioid cellular morphology can be seen in clinically benign usual angiomyolipomas (AMLs), we divide epithelioid AMLs into those without and with atypia, the latter category associated in the literature with malignant potential. We herein report the histologic spectrum and biologic behavior of 40 consecutive cases of epithelioid AML with atypia and assess whether cases can be stratified prognostically based on clinical and pathologic features. Atypical epithelioid cells were defined as atypical polygonal cells with abundant cytoplasm, vesicular nuclei, prominent nucleoli, and nuclear size that exceeds x2 the size of adjacent nuclei. ⋯ All of these were more frequently observed in clinically malignant cases: older age, larger tumor size, higher percentage of epithelioid component, severe atypia, higher percentage of atypical cells, higher mitotic count, atypical mitotic figures, necrosis, lymphovascular invasion, and renal vein invasion. Using these features, we developed a predictive model of 4 atypical features that included: (1) > or =70% atypical epithelioid cells, (2) > or =2 mitotic figures per 10 hpf, (3) atypical mitotic figures, and (4) necrosis; the presence of 3 or all of the features was highly predictive of malignant behavior. This model accurately categorized 78% of clinically malignant and 100% of the clinically benign epithelioid AMLs with atypia.
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Am. J. Surg. Pathol. · Apr 2010
SALL4 represents fetal gut differentiation of gastric cancer, and is diagnostically useful in distinguishing hepatoid gastric carcinoma from hepatocellular carcinoma.
The novel stem cell marker SALL4 has been identified as a diagnostic marker of germ cell tumors, especially yolk sac tumors, in gonadal organs. To clarify the significance of SALL4 as an oncofetal protein, we investigated SALL4 expression by immunohistochemistry in non-neoplastic stomach and gastric carcinoma with particular emphasis on á-fetoprotein (AFP)-producing gastric carcinoma, as AFP-producing gastric carcinoma shares expression of AFP and glypican 3 (GPC3) with yolk sac tumors and hepatic neoplasms. A total of 338 gastric carcinomas, 60 hepatocellular carcinomas, and 48 cholangiocellular carcinomas were studied by immunohistochemistry on tissue microarrays. ⋯ In addition, SALL4 expression was completely negative in hepatoblastoma (n=6) and hepatocellular carcinoma (n=60). SALL4 is an oncofetal protein similar to AFP and GPC3, but it represents fetal gut differentiation in gastric carcinoma. SALL4 is a sensitive marker for AFP-producing gastric carcinoma and is especially useful to distinguish hepatoid gastric carcinoma from hepatocellular carcinoma.
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Am. J. Surg. Pathol. · Apr 2010
Comparative StudyAccurately assessing her-2/neu status in needle core biopsies of breast cancer patients in the era of neoadjuvant therapy: emerging questions and considerations addressed.
Emerging data show that patients with operable, HER-2/neu overexpressed/amplified breast carcinomas have significantly better responses (more frequently obtaining pathologic complete response and greater percent disease-free survival) when treated with trastuzumab (Herceptin) simultaneously with neoadjuvant chemotherapy than with chemotherapy alone. With the increasing use of neoadjuvant therapies, clinicians require information on biomarkers including HER-2/neu status at the time of needle core biopsy. Concordance rates between fluorescence in situ hybridization (FISH)-determined HER-2/neu status on needle core biopsies and on subsequent excisional biopsies of the same tumor have not been well studied. Moreover, the practice of automatically performing ("reflexing") 2+ immunohistochemical (IHC) staining needle core biopsies for FISH analysis on the same sample needs to be validated. In this study, we set out to (1) determine the accuracy of HER-2/neu status as determined by FISH on needle core biopsy material compared with FISH on the subsequent excisional biopsy of the same tumor with special consideration of IHC 2+staining cases and (2) determine the constancy of HER-2/neu status in pre-neoadjuvant and post-neoadjuvant chemotherapy-treated tumor in the form of needle core biopsy and excisional biopsy samples, respectively. ⋯ Excellent overall concordance was achieved between FISH-determined HER-2/neu status on the needle core biopsy and that determined on the subsequent excisional biopsy of the same tumor. These results suggest that intratumoral heterogeneity of HER-2/neu assessed by FISH is not a significant confounding factor when analyzing smaller sized samples. Furthermore, 79% of 2+IHC staining needle core biopsy cases showed concordant FISH results in the needle core biopsy and subsequent excisional biopsy specimens. Our results show good concordance, however, larger cohorts need to be studied to verify this finding. HER-2/neu status remains unchanged in the majority of cases when comparing pre-neoadjuvant and post-neoadjuvant chemotherapy-treated specimens.
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Am. J. Surg. Pathol. · Mar 2010
Comparative StudyB-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements are aggressive neoplasms with clinical and pathologic features distinct from Burkitt lymphoma and diffuse large B-cell lymphoma.
B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements, also known as "double-hit" lymphomas (DHL), are rare neoplasms characterized by highly aggressive clinical behavior, complex karyotypes, and a spectrum of pathologic features overlapping with Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and B-lymphoblastic lymphoma/leukemia (B-LBL). The clinical and pathologic spectrum of this rare entity, including comparison to other high-grade B-cell neoplasms, has not been well defined. We conducted a retrospective analysis of clinical and pathologic features of 20 cases of DHL seen at our institution during a 5-year period. ⋯ DHL is a high-grade B-cell neoplasm with a poor prognosis, resistance to multiagent chemotherapy, and clinical and pathologic features distinct from other high-grade B-cell neoplasms. Familiarity with the morphologic and immunophenotypic spectrum of DHL is important in directing testing to detect concurrent IGH-BCL2 and MYC rearrangements when a karyotype is unavailable. The aggressive clinical behavior and combination of genetic abnormalities seen in these cases may warrant categorization as a separate entity in future classifications and call for novel therapeutic approaches.