Combined Tumors in Hematolymphoid Neoplasms: Case Series of Histiocytic and Langerhans Cell Sarcomas Arising From Low-Grade B-Cell Lymphoma

We report an index case of histiocytic sarcoma arising in a 70-year-old patient with long-standing chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The patient presented in 2017 with painful, enlarging swelling of the left neck. He had remote history of cutaneous squamous cell carcinoma with no sign of recurrence, and his CLL/SLL was thought to be in remission. Computed tomography showed mild splenomegaly and multifocal lymphadenopathy including a 3-cm left neck mass. Biopsy of the left neck mass showed CLL/SLL with associated histiocytic sarcoma. Flow cytometry demonstrated a B cell neoplasm with CLL/SLL phenotype. Despite radiation therapy, he expired 3 months after presentation. Two similar cases (CLL/SLL and histiocytic sarcoma, follicular lymphoma and Langerhans cell sarcoma) from another institution are also illustrated. The pathological features of combined tumors in lymphoid neoplasms, a general framework to the work-up to determine interrelatedness of tumor components, and the clinical relevance are discussed.

Exploring the Histogenesis of Ovarian Mucinous and Transitional Cell (Brenner) Neoplasms and Their Relationship With Walthard Cell Nests: A Study of 120 Tumors

Context.—The origin of and relationship between ovarian mucinous and transitional cell (Brenner) neoplasms are enigmatic. The reported association ranges from 1% to 16%, and whether there is an association with Walthard cell nests is unknown. Objective.—To clarify the histologic relationship between mucinous and Brenner tumors. Design.—A total of 40 mucinous cystadenomas, 67 Brenner tumors, and 13 combined tumors were studied. Peritoneal surfaces were examined for Walthard nests in 83 patients compared with 272 controls. Results.—A total of 25% of tumors with a mucinous component contained a Brenner component, and 16% of tumors with a Brenner component contained a mucinous component. Most calcifications were spiculated (nonpsammomatous). In 6 combined tumors, the relative volume of the 2 components was less than 1:3000 (transitional-mucinous). Walthard nests were found in 50% of patients with Brenner tumors and 59% of patients with mucinous tumors. This was significantly higher than the 28% found in controls (P = .002 and P < .001, respectively). The number of fallopian tube blocks examined was correlated with the likelihood of finding Walthard nests, and accordingly, sampling accounted for 39% of the increase with Brenner tumors but strengthened the association with mucinous tumors. Conclusions.—The strong association of mucinous and transitional cell components, similar type of calcification, complementary size distributions, and frequent identification of a transitional component in the face of an exceedingly small estimated proportion of that component suggest that this association has been underestimated. The association of Brenner tumors with Walthard nests, although significant, appears weak and not strongly supportive of a histogenetic relationship. The stronger association of Walthard nests with mucinous tumors remains unexplained.

Combined Hepatocellular Cholangiocarcinomas; Analysis of a Large Database

Aim Combined hepatocellular cholangiocarcinoma (combined tumor) has been described as either a variant of hepatoma or a variant of cholangiocarcinoma. Prior studies evaluated fewer than 50 patients with combined tumors, precluding multivariate analyses. Posited was the notion that analysis of a large database would yield more definite answers. Methods This study used SEER (Surveillance, Epidemiology, and End Results Program of the National Cancer Institute) to analyze 282 combined tumors, 2,035 intrahepatic cholangiocarcinomas, and 19,336 hepatomas between the years 1973-2003. Multinomial logit regression calculated point estimates and 95% confidence intervals (c.i.) for relative risk (rr). Cox regression calculated point estimates and 95% confidence intervals (c.i.) for hazard ratios (ĥ). Results Men less often had cholangiocarcinomas than they had combined tumors (rr = 0.63, c.i. = 0.49-0.81). Hepatomas less often than combined tumors presented with distant spread (rr = 0.56, c.i. = 0.43-0.72). Men (rr = 1.50, c.i. = 1.17-1.93) and patients with a known Asian or Pacific birthplace (rr = 2.36, c.i. = 1.56-3.56) more often had hepatomas than they had combined tumors. Among patients not known to have an Asian/Pacific birthplace, a diagnosis of cholangiocarcinoma (ĥ = 0.72, c.i. = 0.63-0.82) or hepatoma (ĥ = 0.75, c.i. = 0.66-0.86) provided a better prognosis than did a diagnosis of combined tumor. Conclusion Combined tumors differ from hepatomas and cholangiocarcinomas in terms of distribution and survival patterns in the population; they should be considered neither cholangiocarcinomas nor hepatomas.

Clonality of Combined Tumors

Context.—Tumors with mixed morphologic patterns (combined tumors) are sometimes encountered, and questions often arise regarding the mechanism of molecular pathogenesis of each component and their relationships. Objective.—To determine whether different components of combined tumors contain the same or different genetic alterations, thus providing evidence for their clonality. Materials and Methods.—Six combined tumors with 2 components (in each case, both components showed epithelial differentiation morphologically) were studied by microdissecting tumor cells from each morphologic area followed by loss of heterozygosity analysis. Results.—In 1 of the cases studied, the different morphologic areas contained different patterns of genetic alterations. In the remaining 5 cases, the different morphologic areas harbored identical genetic changes in the chromosome regions studied. The latter group, interestingly, included a colonic tumor with an area of tubulovillous adenoma and an area of neuroendocrine carcinoma, and 2 lung tumors with squamous carcinoma and small cell carcinoma components. Conclusions.—Our results suggest that in the majority of combined tumors, cells with different phenotypes share similar genotype and may arise from a single precursor cell. However, in a minority of these tumors, different areas may be derived from different precursor cells.