The purpose of this study was to examine predictors of lymph node metastases (LN+) or extrauterine disease (ED) in low grade (FIGO grades 1 or 2) endometrioid carcinoma (LGEC) in a multi institutional setting. For LGEC with and without LNM or ED, each of the 9 participating institutions evaluated patients age, tumor size, myometrial invasion (MI), FIGO grade, % solid component, the presence or absence of papillary architecture, microcystic elongated and fragmented glands (MELF) and single cell/cell cluster invasion (SCI), lymphovascular invasion (LVI), lower uterine segment (LUS) and cervical stromal (CX) involvement and numbers of pelvic (PLN) and para-aortic (PALN) LNs sampled.302 cases were reviewed: LN+ or ED +, 96; LN-/ED-, 208. Patients' ages ranged from 23-91 yrs (median 61). Table 1 summarizes the histopathologic variables that were noted for the LN+ or ED+ group: tumor size ≥2cm, 93/96 (97%), MI >50%, 54/96 (56%), MELF, 67/96 (70%), SCI, 33/96 (34%), LVI, 79/96 (82%), >20% solid, 65/96 (68%), papillary architecture present, 68/96 (72%), LUS involved, 64/96 (67%) and CX involved, 31/96 (32%). For the LN-/ED- group, the results were as follows: tumor size ≥2cm, 152/208 (73%), MI >50%, 56/208 (27%), MELF, 79/208 (38%), single cell invasion, 19/208 (9%) , LVI, 56/208 (27%), >20% solid, 160/208 (77%), papillary architecture present, 122/208 (59%), LUS involved, 77/208 (37%), CX involved, 31/208 (15%). There was no evidence of a difference in the number of pelvic or para-aortic LNs sampled between groups (p=0.9 and 0.1, respectively). Following multivariate analysis, depth of myometrial invasion, cervical stromal involvement, lymphovascular space invasion, and the single cell pattern of invasion emerged as significant predictors of advanced stage disease. Although univariate analysis pointed to LUS involvement, MELF pattern of invasion, and papillary architecture as possible predictors of advanced stage disease, these were not shown to be significant by multivariate analysis. This study validates MI, CX involvement and LV as significant predictors of LN+ or ED. The association of SCI pattern with advanced stage LGEC is a novel finding.
Chronic myeloid leukemia (CML) accounts for approximately 15% of adult leukemias. Forty percent of patients with CML are asymptomatic, in whom the disease is detected solely based on laboratory abnormalities. Since the introduction of tyrosine kinase inhibitor therapy in 2001, CML has become a chronic disease for the majority of patients. Primary care physicians may be the first to recognize a new diagnosis of CML. In patients with known CML, the primary care physician may be the first to detect disease progression or adverse effects to therapy. This article provides an overview of the clinical presentation, diagnostic approach, and treatment considerations of CML.
Rectal neuroendocrine tumors (NETs) can be classified by histologic pattern and secretory products. Recently, rectal NETs have been noted to exhibit immunohistochemical (IHC) positivity for Islet 1 and PAX8, which are generally considered markers for NETs of pancreatic origin. In this study, we sought to characterize the IHC staining profile of rectal NETs and determine whether there was any correlation between the histologic pattern of rectal NETs and their IHC profile. Fifty-six primary rectal NETs were histologically reviewed and stained with antibodies against Islet 1, PAX8, CDX2, chromogranin A, and synaptophysin. In a subset of 31 cases, immunoreactivity for serotonin, pancreatic polypeptide (PP), and prostatic acid phosphatase (PAP) was also studied. By morphology, the tumors studied included 55 % trabecular, 27 % solid nested, 4 % acinar, and 14 % mixed patterns. Islet 1 was positive in 89 % and PAX8 in 79 % of cases. CDX2 was negative in all 56 cases. Cytoplasmic staining was observed for chromogranin A in 30 % of cases and for synaptophysin in all 56 cases. Cytoplasmic staining for serotonin, PP, and PAP was present in 16, 61, and 97 % of cases, respectively. There was no correlation between histologic pattern and IHC staining pattern with any of the antibodies studied. We have demonstrated that Islet 1 and PAX8 are not entirely specific for NETs of pancreatic origin, as they are expressed in a majority of rectal NETs. Since rectal NETs may show an IHC staining profile which mirrors that of pancreatic NETs (Islet 1 and PAX8-positive, CDX2-negative), a metastatic rectal NET should be considered in the differential diagnosis and ruled out clinically in the work-up of a metastatic NET of unknown primary origin which exhibits this staining profile.
Endometrial adenocarcinoma is the most common gynecologic cancer in the United States. The prognosis is generally favorable, however, a significant number of patients do develop local or distant recurrence. The most common site of recurrence is vaginal. Our aim was to better characterize patients with vaginal recurrence of low-grade endometrioid adenocarcinoma with respect to associated tumor parameters and clinical outcome. We compiled 255 cases of low-grade (FIGO Grade I or II) endometrioid adenocarcinoma on hysterectomy specimens with lymph node dissection. A total of 113 cases with positive lymph nodes or recurrent disease were included in our study group. Seventy-three cases (13 Grade 1, 60 Grade 2) developed extravaginal recurrence and 40 cases (7 Grade 1, 33 Grade 2) developed vaginal recurrence. We evaluated numerous tumor parameters including: percentage myoinvasion, presence of microcystic, elongated, and fragmented pattern of myoinvasion, lymphovascular space invasion, and cervical involvement. Clinical follow-up showed that 30% (34/113) of all patients with recurrent disease died as a result of their disease during our follow-up period, including 31 (42.5%) with extravaginal recurrence and 3 (7.5%) with primary vaginal recurrence (P=0.001). The 3 patients with vaginal recurrence developed subsequent extravaginal recurrence before death. Vaginal recurrence patients show increased cervical involvement by tumor, but lack other risk factors associated with recurrent disease at other sites. There were no deaths among patients with isolated vaginal recurrence, suggesting that vaginal recurrence is not a marker of aggressive tumor biology.
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