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Intradermal melanocytes in the setting of melanoma represent a diagnostic challenge to dermatopathologists as their presence may represent superficially invasive melanoma vs benign nevus cells or reactive dermal melanocytes. Previous dermatologic literature suggests that the absence of cytologic atypia in intradermal melanocytes and their presence in nonmelanocytic neoplasms lends to their characterization as reactive, benign, melanocytic proliferation. A 67-year-old female presented for evaluation of a 10-mm irregularly pigmented dark brown macule on the left cheek. Initial shave biopsy showed transected malignant melanoma measuring at least 0.6 mm in thickness. Multiple reexcision specimens demonstrated residual melanoma with banal appearing intradermal epithelioid melanocytes within and surrounding the scar. The melanocytes tracked into the skin graft, which had previously been free from involvement. Positron emission tomography-computed tomography (PET CT) and lymph node biopsies did not show evidence of metastatic melanoma. Ten months after her diagnosis and following five surgical excisions, the patient was diagnosed with metastatic melanoma to the brain and succumbed to intracranial hemorrhage. We present a case in which paracicatricial melanoma may simulate benign paracicatricial melanocytic hyperplasia. These findings have significant therapeutic and prognostic implications for the practicing dermatologist and dermatopathologist., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recurrence in the liver following hepatic resection for metastatic colorectal carcinoma is a predictable phenomenon, occurring in about two-thirds of patients who develop recurrence. There are few data, however, about the value of repeated hepatic resection in patients who have a recurrence in the liver following initial resection of their hepatic metastases. We have reviewed our experience with 10 patients (of whom 9 were evaluable), culled from a series of 74 patients who had an initial hepatic resection for metastatic colorectal carcinoma. There were seven men and two women, mean age 52 (range 34-75 years). Duke's stages of the primary cancer were B1 in two patients, B2 in one patient, and C2 in six patients. Most of the patients had elevated carcinoembryonic antigen (CEA) and constitutional symptoms as indications for the second-look procedure. There was one surgical death due to hepatic failure in a patient who required a trisegmentectomy. The average interval between the first and second hepatic resections was 21 months. The estimated 1- and 5-year actuarial survivals from the second liver resection were 78% and 23%, respectively. The median survival was 41 months from the first resection (range 14-100 months) and 16 months from the second resection (range 0-92 months). In conclusion, repeat hepatectomy for recurrent liver metastases is a viable option for the well selected patient. It is a low risk surgical procedure and may augment survival in the patient with well documented metastases limited to the liver.

There are approximately 27,000 new cases of carcinoma of the pancreas each year and most afflicted patients will die of the disease. Although smoking is a common denominator, chronic pancreatitis is considered an important precursor lesion in a smaller number of cancers. Pancreatic cancer is primarily a disease of the pancreatic ducts. The molecular events are under intense study, but c-K-ras mutation is involved in approximately 80% of the cases and p53 to a slightly lesser degree (60-80%). Early manifestations are usually occult, but jaundice is a common manifestation in patients with cancers of the pancreatic head. Thin-slice computed tomography, portography, and endoscopic retrograde cholangiopancreatography are currently the most sensitive detection techniques. The developing use of endoscopic ultrasound and laparoscopy appear to enhance detection and are under evaluation. In many patients with advanced disease, endoscopic bypass may eliminate the need for unnecessary surgery, although gastrointestinal bypass is still required in some patients (10-15%). Curative resection is possible in selected patients (perhaps 10-15%), with expectation of extended survival ranging from 6->20% in some series. The survival differences may be related to stage, patient selection, and the expertise of the operative team. Preoperative chemotherapy/radiation is under study and may improve outcome. Clinical trial participation is essential for improvement in treatment outcomes.

Background: Several studies have provided evidence suggesting that platelets play a key role in tumor metastasis. A number of antiplatelet agents have been used to prevent tumor metastasis in animal models and humans. Antiplatelet agents, dipyridamole (adenosine transport inhibitor), and RA-233 (inhibitor of cAMP PDE) were used to prevent tumor-cell-platelet interactions both in in vitro and in vivo systems; however, the data were not very conclusive., Methods: Our studies used dipyridamole and RA-233 alone and in combination to investigate their effects on human pancreatic tumor cells (RWP-2)-induced platelet aggregation in human blood and on hepatic metastasis in nude mice. To examine effects of dipyridamole and RA-233 on liver metastasis, the tumor cells (RWP-2) were injected intrasplenically in nude mice grouped into control, dipyridamole (8 mg/kg), RA-233 (8 mg/kg), and dipyridamole plus RA-233 (8 mg/kg each). The agents were administered intraperitoneally 1 hour before and 24 hours after the tumor cell injection., Results: When dipyridamole and RA-233 were used alone, only weak to moderate effects were seen on RWP-2 tumor cell-induced platelet aggregation. However, these agents, when combined, strongly inhibited the tumor cell-induced aggregation in human platelet-rich plasma. In tumor metastasis experiments, reductions of approximately 70% in hepatic nodules and 90% in surface area occupied by the tumor were seen with the combination treatment (dipyridamole plus RA-233) as compared with the control group of mice., Conclusions: This study suggests that the combination of dipyridamole and RA-233 provides an effective intervention for the antithrombotic approach to the treatment of cancer metastases.

Background: The secretion of carcinoembryonic antigen (CEA) by many colorectal tumors is associated with a worse prognosis and a greater likelihood of metastases. The exact biologic function of CEA is not known. In the literature, it has been postulated CEA may be a tumorigenicity-enhancing factor., Methods: Ten different human colonic adenocarcinoma cell lines (RW-7213, RW-2982, LS174T, SW1116, RW-5928, DLD-2, SW-48, DLD-1, SW-480, and HCT-8) with a wide range of CEA production (from undetectable to 5200 ng/ml in culture medium) were injected into the spleens of groups of nude mice as a model for experimental hepatic metastasis., Results: There was a wide range in local tumorigenicity in the spleen (from 0-90%) and in liver metastases (from 0-70%). The capacity to grow in both liver and spleen was associated with CEA production. The four cell lines that secreted the highest amounts of CEA produced the highest tumorigenicity in the spleen (67-90%) with frequent liver colonization (25-70%). The two cell lines that secreted no detectable CEA produced neither splenic tumors nor hepatic colonies. Low-level CEA production was associated with intermediate and more variable tumorigenicity., Conclusions: There was an association between CEA secretion and the ability of 10 different colorectal cell lines to grow in nude mouse spleen and liver models.

A cell line with high metastatic capacity to the liver was established by sequential passages of a human pancreatic cancer cell line through the nude mouse liver. A subline, L3.5, established after five passages of the fast-growing variant (FG) of the human pancreatic cancer COLO 357 through the nude mouse liver produced extensive hepatic metastases in 100% of experimental animals when injected into the spleen. The incidence of pulmonary metastases decreased from 43% for FG to 9% for L3.5. The L3.5 cell line showed aggressive growth with almost complete replacement of the hepatic parenchyma in one third of the mean time required for the development of macroscopic metastases of FG in the liver after splenic injections of tumor cells. This study indicates that the nude mouse provides a good model for in vivo selection of metastatic cells from human pancreatic cancer. The L3.5 cell line will be valuable in the study of human pancreatic cancer metastasis, particularly in the area of survival and growth of metastatic cells in the microenvironment of the liver.

A previous study reported the results of a radioimmunoassay that analysed immune complexes (IC) with a specific labeled polyclonal antibody for the detection of the early stages of colon cancer. In order to investigate further the possible clinical use of this assay, a blind study that screened 505 patients referred for colonoscopy, compared their pathology reports with the results of four assays that measure levels of circulating tumor markers. These were CEA, AFP, Ca 19-9, and our previously described radioimmunoassay (RIA). Of the patients with no malignancies, the results that were in the normal range were as follows: CEA-473/495 (95.6 per cent), Ca 19-9-486/495 (98.2 per cent) and our RIA-488/495 (98.6 per cent). AFP levels were in the normal range for all patients in the study. The only assay to identify any Dukes' C and D patients was Ca 19-9, which detected 2/3 (67 per cent). Of the patients with Dukes' A and B colon cancer, CEA only identified 1/7 (14 per cent), AFP and Ca 19-9 0/7 (0 per cent), and our own RIA 5/7 (71 per cent). The positive results of our assay were significantly different from those of the other three assays with p values all less than 0.05. These preliminary results suggest that this RIA, because of its ability to detect the early stages of colon cancer, may be an effective complement to the currently available assays. The combination may provide a more comprehensive evaluation in monitoring colon cancer.

A radioimmunoassay was developed for the detection of the early stages of colon cancer by analysis of immune complexes (IC) with a specific polyclonal antibody. Human colon cancer cells were grown in a capillary culture system to provide unaltered antigens for the development of a specific antibody. The antibody was labeled with iodine 125 (125I) and used to analyze the antigen component of IC removed from whole serum. The assay was positive in 50% and 88% of known Dukes' A and Dukes' B colon cancer patients, respectively. It was also positive for only 25% of Dukes' C and 14% of Dukes' D patients, possibly because of the decreased quantity of specific IC found in the late stages of colon cancer. A blind study of patients referred for colonoscopy compared pathology diagnosis with the test results. The assay was positive for one patient with a polypoid adenocarcinoma (Dukes' B) and one with a villous adenoma and negative for 38 patients with benign polyps and 43 with no polyps. The assay was negative for all patients with stomach cancer and inflammatory bowel diseases and positive for about 10% of the patients with pancreas or breast cancer. The results of this preliminary investigation suggest that this radioimmunoassay may be useful for the detection of the early stages of colon cancer.

Metastasis is a multistep phenomenon in which platelets appear to play an important role. This study examined several compounds for their effects on experimental hepatic metastasis and on human pancreatic tumor cell-platelet interactions. Prostacyclin (PGI2) and forskolin (stimulators of platelet adenylate cyclase) and ketoconazole (inhibitor of lipoxygenese and thromboxane synthetase) were used in order to investigate their effects on hepatic metastases from a human pancreatic tumor cell (RWP-2) in the nude mouse. The tumor cells were injected intrasplenically and the animals were divided into control, prostacyclin (PGI2 200 micrograms), forskolin (150 micrograms), and ketoconazole (180 micrograms) groups. All three drugs were administered intraperitoneally 30 minutes before and 24 hours after the tumor cell injections. Statistically significant differences were observed between control and treated groups in tumor surface area (P less than 0.001), percentage of liver surface area occupied by tumor (P less than 0.001), and number of tumor colonies (P less than 0.004 for prostacyclin, P less than 0.005 for forskolin, and P less than 0.001 for ketoconazole). These agents also strongly inhibited RWP-2-induced platelet aggregation in human platelet-rich plasma.

A retrospective review of 483 women who had metastatic breast cancer and were treated between 1942 and 1975 was carried out to examine the effects of improving and aggressive palliative modalities on patient survival. There was a steady increase in the proportion of patients treated by chemotherapy and/or hormonal ablative therapy. Additive hormonal therapy, irradiation, and surgery for palliation decreased in frequency during the same period. Survival time from the first recurrence did not appear to increase in these patients over the period of this study. In spite of increasingly sophisticated palliative therapies, the survival time of patients with metastasis did not appear to be significantly prolonged.

A case of mesenchymal chondrosarcoma of the kidney, with osseous metastases, is presented in this article, and the clinical, radiologic, and histopathologic features of this uncommon neoplasm are discussed. The addition of this case to those previously reported in the literature brings the total number of reported cases of mesenchymal chondrosarcoma of extraskeletal origin to 42. None of the previously reported cases originated from the kidney. The metastatic pattern of this case illustrates the propensity of mesenchymal chondrosarcoma to metastatize to unusual locations.