Carcinoma and multiple lymphomas in one patient: establishing the diagnoses and analyzing risk factors

Multiple malignancies may occur in the same patient, and a few reports describe cases with multiple hematologic and non-hematologic neoplasms. We report the case of a patient who showed the sequential occurrence of four different lymphoid neoplasms together with a squamous cell carcinoma of the lung. A 62-year-old man with adenopathy was admitted to the hospital, and lymph node biopsy was positive for low-grade follicular lymphoma. He achieved a partial remission with chemotherapy. Two years later, a PET-CT scan showed a left hilar mass in the lung; biopsy showed a squamous cell carcinoma. Simultaneously, he was diagnosed with diffuse large B cell lymphoma in a neck lymph node; after chemo- and radiotherapy, he achieved a complete response. A restaging PET-CT scan 2 years later revealed a retroperitoneal nodule, and biopsy again showed a low-grade follicular lymphoma, while a biopsy of a cutaneous scalp lesion showed a CD30-positive peripheral T cell lymphoma. After some months, a liver biopsy and a right cervical lymph node biopsy showed a CD30-positive peripheral T cell lymphoma consistent with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. Flow cytometry and cytogenetic and molecular genetic analysis performed at diagnosis and during the patient’s follow-up confirmed the presence of two clonally distinct B cell lymphomas, while the two T cell neoplasms were confirmed to be clonally related. We discuss the relationship between multiple neoplasms occurring in the same patient and the various possible risk factors involved in their development

市民社会のプレーヤー交代劇と政治-仁平典宏の<贈与のパラドックス>論を読み解く-

千葉大学大学院人文社会科学研究科研究プロジェクト報告書第257集『都市コミュニティにおける相互扶助と次世代育成』水島治郎 編Sustainable Urban Communities: Communality and Generativity Report on the Research Projects No.25

Intestinal-type endocervical adenocarcinoma in situ: an immunophenotypically distinct subset of AIS affecting older women.

peer reviewedConventional endocervical adenocarcinoma in situ (cAIS) is typically strongly and diffusely positive for p16 with a high Ki67 index consistent with its frequent association with high-risk human papillomavirus (HPV) infection. The intestinal variant (iAIS) is less common, and its relationship to HPV infection has not been thoroughly examined. This study compares the clinicopathologic features, frequency of HPV infection, and expression of CDX2 and surrogate biomarkers of HPV infection (p16, Ki67) in cAIS with those of iAIS. A total of 86 cases with a diagnosis of AIS (49 iAIS, 37 cAIS) were identified from our multi-institutional files. Of these, 13 iAIS and 20 cAIS cases had slides and tissue available for histopathologic review, immunohistochemical analysis, and molecular tests. All 86 cases were used to evaluate clinical parameters; however, HPV DNA analysis and immunohistochemical analysis for p16, MIB-1, CDX2, and p53 were performed only on those cases with available slides or paraffin blocks. The average age at diagnosis was significantly higher in iAIS compared with that in cAIS (44.5 vs. 32.6 y) (P=0.0001). All 20 cAIS cases showed moderate to strong and diffuse p16 staining; however, only 9/13 iAIS cases showed this degree of p16 staining, whereas 4/13 (31%) iAIS cases showed weak and patchy distribution (P<0.02). Only 6/9 (67%) iAIS cases were positive for either HPV type 18 (5) or 33 (1), in contrast to 11/11 conventional cAIS (P=0.04). Similarly, 12/14 cAIS, but only 5/13 iAIS, cases showed a high Ki67 proliferative index. CDX2 was positive in all iAIS cases, whereas p53 was negative. Most iAIS cases are positive for high-risk HPV and show moderate to strong and diffuse p16 staining; however, a subset of iAIS shows variable staining with p16 and Ki67, is not associated with HPV, and occurs in a distinctly older age group suggesting an alternative pathogenesis. Awareness that iAIS can show variable staining for p16 and Ki67 is important when resolving problematic endocervical lesions, particularly in small biopsies with unusual p16 staining patterns

PIK3CA Mutation in Colorectal Cancer: Relationship with Genetic and Epigenetic Alterations1

Somatic PIK3CA mutations are often present in colorectal cancer. Mutant PIK3CA activates AKT signaling, which up-regulates fatty acid synthase (FASN). Microsatellite instability (MSI) and CpG island methylator phenotype (CIMP) are important molecular classifiers in colorectal cancer. However, the relationship between PIK3CA mutation, MSI and CIMP remains uncertain. Using Pyrosequencing technology, we detected PIK3CA mutations in 91 (15%) of 590 population-based colorectal cancers. To determine CIMP status, we quantified DNA methylation in eight CIMP-specific promoters [CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1] by real-time polymerase chain reaction (MethyLight). PIK3CA mutation was significantly associated with mucinous tumors [P = .0002; odds ratio (OR) = 2.44], KRAS mutation (P < .0001; OR = 2.68), CIMP-high (P = .03; OR = 2.08), phospho-ribosomal protein S6 expression (P = .002; OR = 2.19), and FASN expression (P = .02; OR = 1.85) and inversely with p53 expression (P = .01; OR = 0.54) and β-catenin (CTNNB1) alteration (P = .004; OR = 0.43). In addition, PIK3CA G-to-A mutations were associated with MGMT loss (P = .001; OR = 3.24) but not with MGMT promoter methylation. In conclusion, PIK3CA mutation is significantly associated with other key molecular events in colorectal cancer, and MGMT loss likely contributes to the development of PIK3CA G>A mutation. In addition, Pyrosequencing is useful in detecting PIK3CA mutation in archival paraffin tumor tissue. PIK3CA mutational data further emphasize heterogeneity of colorectal cancer at the molecular level