Granulocyte Colony-Stimulating Factor–Producing Cholangiocellular Carcinoma

A 61-year-old female was admitted to our hospital with epigastric pain and fever. The laboratory data showed severe inflammatory reactions. Computed tomography revealed an irregular tumor in the left hepatic lobe and swelling of lymph nodes. ¹⁸F-fluorodeoxy-glucose positron emission tomography (FDG-PET) showed high uptake by the tumor, with diffuse uptake in the spine. Based on the elevated leukocyte count and FDG-PET findings, the patient was diagnosed with a granulocyte colony-stimulating factor (G-CSF)-producing tumor (G-CSF, 213 pg/mL). We performed left trisegmentectomy of the liver, bile duct resection, and lymph node dissection. Histologically, the tumor was a poorly differentiated adenocarcinoma with some lymph nodes metastasis. Immunohistochemical staining of the tumor cells was positive for G-CSF. Therefore, the tumor was diagnosed as G-CSF–producing cholangiocellular carcinoma. The inflammatory reactions and serum G-CSF level transiently improved immediately after surgery. However, 1 month later, the leukocyte count and serum G-CSF level increased again, and recurrence was observed in the remnant liver. The patient died 3 months after the operation. G-CSF–producing cholangiocellular carcinoma is rare. This tumor progresses rapidly, and surgical treatment for advanced condition should be carefully selected.Key words: Granulocyte colony-stimulating factor, Cholangiocellular carcinoma, FDG-PET, Immunohistochemistry, LeukocytosisGranulocyte colony-stimulating factor (G-CSF)-producing tumors were first reported in 1977.¹ G-CSF-producing cholangiocellular carcinomas (CCCs) are rare, with only 5 other reported cases. We herein report a surgical case of G-CSF–producing CCC with early recurrence and include bibliographic comments.     

CD56 may be a more useful immunohistochemical marker than somatostatin receptor 2A for the diagnosis of phosphaturic mesenchymal tumors

Phosphaturic mesenchymal tumors (PMTs) are the most typical cause of tumor-induced osteomalacia (TIO) associated with mesenchymal neoplasms. Specifically, TIO is attributed to the production of phosphatonins, such as fibroblast growth factor 23 (FGF23), participating in the homeostasis of phosphate. Although immunohistochemistry (IHC) for FGF23 showed characteristic positive staining in PMTs, FGF23 antibodies that can be used for the reliable diagnosis of PMTs are hard to obtain in common pathology laboratories. Somatostatin receptor 2A (SSTR2A) has been previously proposed as an alternatively useful marker for the diagnosis of PMTs. However, SSTR2A is not commonly utilized in pathological laboratories. The CD56 marker is a useful alternative that is comparable to SSTR2A and is similar considering the sensitivity. Even in cases of PMTs originating in the bones, ethylenediaminetetraacetic acid-based decalcification for tissue processing does not seem to affect the IHC of CD56. As CD56 immunopositivity in mesenchymal tumors is limited, it also has some degree of specificity for PMTs. Thus, when PMTs are suspected, the use of CD56 is recommended.     

Melanotic oncocytic metaplasia of the nasopharynx: a case report with a focus on immunohistochemical analyses and literature review

Melanotic oncocytic metaplasia (MOM) of the nasopharynx is an extremely rare lesion, with only 21 cases reported in English literature to date. MOM typically occurs near the Eustachian tube opening in Asian men in their 60 s to 70 s. Here, we present a case of MOM in a 57-year-old Japanese man who is a heavy smoker. The patient did not have complaints; MOM was diagnosed incidentally as 4 flat elevated lesions with brown to black discoloration, ranging from 2 to 3 mm in maximal diameter, were found in the right torus tubarius. On suspecting melanoma, the largest lesion was biopsied. Microscopic examination identified both oncocytic metaplasia and melanin pigmentation of the epithelium in the same gland. Upon immunohistochemical examination, melanocytes displayed reactivity for 3 out of 4 melanocytic markers; immunopositivity for S-100 protein, Melan-A, and MITF and immunonegativity for HMB-45 was observed. Normal melanocytes in the nearby surface respiratory epithelium displayed the same pattern of immunoreactivity. Immunopositivity for S-100 protein and immunonegativity for HMB-45 have been previously reported in MOM. Reduction of stimulation of melanocytes in a longstanding lesion like MOM may explain the immunonegativity for HMB-45. S-100 protein, in conjunction with more specific marker for melanocytes, Melan-A or MITF, could prove the definite presence of melanocytes in this case of MOM. As it has been shown by previous reports that MOM pursues a benign course, it will be sufficient to follow up the patients regularly for the remaining 3 lesions.     

A neurogenic tumor containing a low-grade malignant peripheral nerve sheath tumor (MPNST) component with loss of p16 expression and homozygous deletion of CDKN2A/p16: a case report showing progression from a neurofibroma to a high-grade MPNST

Development of malignant peripheral nerve sheath tumors (MPNSTs) is a stepwise process that involves the alteration of many cell cycle regulators and the double inactivation of the NF1 gene. Inactivation of the TP53 gene and deletion of the CDKN2A/p16 gene are known to play an important role in the process. Herein, we present a 19-year-old man with a familial history of neurofibromatosis type 1, in whom the tumor arose from the intercostal nerve and showed 3 components: a neurofibroma, a low-grade MPNST, and a high-grade MPNST. Loss of p16 expression and homozygous deletion of the CDKN2A/p16 gene were observed in both the low-grade and the high-grade MPNST. In contrast to low-grade MPNSTs, high-grade MPNSTs generally tend to lose expression of p16 and harbor homozygous deletion of the CDKN2A/p16 gene. Loss of p16 expression and homozygous deletion of the CDKN2A/p16 gene in low-grade MPNST in our case might be related to its progression to high-grade MPNST. To the best of our knowledge, this is the first study correlating the p16 expression status and CDKN2A/p16 gene alteration in low-grade MPNSTs.     

Myxoid epithelioid gastrointestinal stromal tumor harboring an unreported PDGFRA mutation: report of a case and review of the literature

Activating mutations of platelet-derived growth factor receptor α (PDGFRA) are detected in a significant proportion of gastrointestinal stromal tumors (GISTs), in addition to the more frequent mutation in c-kit. GISTs with PDGFRA mutations have been found to have several characteristic morphological features, sometimes allowing to discriminate them from GISTs with c-kit mutations. Among these, epithelioid morphology in tumor cells and tumor-infiltrating mast cells are powerful predictors of PDGFRA mutations. Although myxoid stroma by itself is not so much a reliable predictor of PDGFRA mutation, myxoid stroma in conjunction with epithelioid morphology in tumor cells is a powerful predictor of mutations in this gene. GISTs showing either weak or negative immunoreactivity for c-kit and epithelioid cells with myxoid stroma are called myxoid epithelioid GISTs, which typically show PDGFRA mutation. Herein, we presented a case of a 59-year-old woman with myxoid epithelioid GIST of the stomach. A unique finding in this case was eosinophil infiltration, probably more numerous than mast cells; mast cell infiltration is known to be usually found in myxoid epithelioid GIST. The existence of a similar mechanism in eosinophil and mast cell recruitment via tumor-producing stem cell factor is speculated. Mutational analyses revealed a PDGFRA exon 18 mutation: D842_H845del, D846N. Combined deletion and substitution mutation has been reported in rare instances, but to the best of our knowledge, D846N has not been documented.     

Predictive factors for postoperative tachyarrhythmia after thoracoscopic esophagectomy and the usefulness of landiolol hydrochloride for its treatment

Background

Tachyarrhythmia after esophagectomy is a severe complication that should not be underestimated because of its negative impact. The aims of this study were to clarify the cause and impact of postoperative tachyarrhythmia after thoracoscopic esophagectomy. Additionally, we analyzed the usefulness of landiolol administration for postoperative tachyarrhythmia.

Methods

We evaluated the predictive factors for tachyarrhythmia onset after surgery and its clinical impact in 127 patients who underwent thoracoscopic esophagectomy with extended lymphadenectomy. Moreover, we analyzed the efficacy of landiolol for postoperative tachyarrhythmia.

Results

Tachyarrhythmia developed in 38 of the 127 patients. Multivariate analysis showed that advanced age, heart disease, and hyperlipidemia were associated with postoperative tachyarrhythmia. Hyponatremia, hypoalbuminemia, and leukocytosis on postoperative day 3 were significantly associated with tachyarrhythmia onset. The incidence of all complications and respiratory complications, including pneumonia, was significantly higher in patients with than in those without tachyarrhythmia. The mortality rate in the tachyarrhythmia group tended to be higher than that in the nontachyarrhythmia group. Landiolol as a treatment for tachyarrhythmia immediately decreased heart rate and safely reduced subsequent respiratory complications.

Conclusion

In elderly patients with cardiac disease or hyperlipidemia, surgeons should be alert for the occurrence of tachyarrhythmia after esophagectomy. Postoperative tachyarrhythmia is a marker of morbidities with particular emphasis on respiratory complications. However, it can be adequately managed by landiolol, resulting in fewer respiratory complications. Landiolol might be a safe and convenient agent for managing postoperative tachyarrhythmia after thoracoscopic esophagectomy, resulting in lower mortality and morbidity rates.