A case of Langerhans cell sarcoma on the scalp: Whole‐exome sequencing reveals a role of ultraviolet in the pathogenesis

Langerhans cell sarcoma (LCS) is a high‐grade neoplasm with overtly malignant cytological features and a Langerhans cell phenotype. The underlying genetic features are poorly understood, and only a few alterations, such as those of the MARK pathway‐related genes, CDKN2A and TP53 have been reported. Here we present a 70‐year‐old male with LCS on the scalp and pulmonary metastasis. The multinodular tumor, 3.0 cm in diameter, consisted of diffusely proliferated pleomorphic cells with numerous mitoses (53/10 HPFs). Immunohistochemically, the tumor cells were positive for CD1a, Langerin and PD‐L1, and the Ki‐67 labeling index was 50%. These pathological features were consistent with LCS, and were also observed in the metastatic tumor. Whole‐exome sequencing revealed that both the primary and metastatic tumors harbored a large number of mutations (>20 mutations/megabase), with deletion of CDKN2A and TP53 mutation, and highlighted that the mutational signature was predominantly characteristic of ultraviolet (UV) exposure (W = 0.828). Our results suggest, for the first time, that DNA damage by UV could accumulate in Langerhans cells and play a role in the pathogenesis of LCS. The high mutational burden and PD‐L1 expression in the tumor would provide a rationale for the use of immune checkpoint inhibitors for treatment of unresectable LCS

Squamous Cell Carcinoma of the Scalp after Artificial Hair Implantation

A 48-year-old man with a protruding tumor on the parietal region had undergone treatment of alopecia using artificial synthetic fibers 2 or 3 times a year for 10 years from 30 to 39 years old. Three months before the first consultation at our hospital, he noticed a small tumor that had gradually shown bleeding and discharge, with expansion of the affected area. A diagnosis of squamous cell carcinoma (SCC) was made based on a biopsy, and we resected the tumor with a 1-cm surgical margin from the reddened area around the protruding tumor (14 × 11 cm), including the periosteum membrane. No tight adhesion was found between the periosteum and skull, so we excised the outer table of the skull of the central part (diameter: 8 cm) for a pathological analysis. A pathological study showed moderately differentiated SCC with a negative surgical margin. The whole tumor was surrounded by scar tissue with buried artificial hair implants. The second surgery was performed on the 15th postoperative day. An anterolateral thigh flap was divided into 2 flaps to fit the circle-shaped wound. This is the second report of SCC developing after artificial hair implantation in the frontal-parietal scalp. The whole protruding tumor was surrounded by scar tissue with buried artificial hair implants. Proving the direct causal relationship between inflammation of scar tissue and SCC generation is difficult; however, our pathological findings support the possibility of the harmful effects of artificial hair implants

A subcentimeter duodenal neuroendocrine neoplasm with a liver metastasis upgraded to G3: a case report

BACKGROUND: Although duodenal neuroendocrine neoplasms (DuNENs) usually have indolent phenotypes, some DuNENs exhibit aggressive clinical manifestations. Tumor size > 1 cm, lymph node metastasis, and high grade have been associated with poor prognosis. However, preoperative risk evaluation is often difficult, because Ki-67 index on biopsy is frequently underestimated due to the intratumor heterogeneity. Here, we present a case of a subcentimeter DuNEN with a low Ki-67 index on endoscopic biopsy, who developed lymph node metastasis and high-grade liver metastasis. CASE PRESENTATION: The patient was a 52-year-old female who presented an epigastric pain. Esophagogastroduodenoscopy revealed a duodenal submucosal lesion with a size of 8 mm. The endoscopic biopsy showed DuNEN with a Ki-67 index of 3.3% (G2 categorized by the World Health Organization 2019 classification). We performed an open partial duodenectomy with adjacent lymph node dissection. Pathological examination of the resected specimens revealed a Ki-67 index of 13.5% (G2) in the "hot spot" and lymph node metastasis. A hepatic low-density area detected on preoperative contrast-enhanced computed tomography appeared to be a liver metastasis on postoperative gadoxetic acid-enhanced magnetic resonance imaging. Subsequently, we performed a laparoscopic partial hepatectomy. Pathological examination of the liver specimen showed a metastatic neuroendocrine tumor with a Ki-67 index of 27.5% (NET-G3). The patient has been alive for 14 months since the hepatectomy. CONCLUSIONS: This case shows the possibility of high malignant potential of DuNEN even if the primary lesion is < 1 cm and has a low Ki-67 index on biopsy

Generation of electromagnetic waves from 0.3 to 1.6 terahertz with a high-T-c superconducting Bi2Sr2CaCu2O8+delta intrinsic Josephson junction emitter

To obtain higher power P and frequency f emissions from the intrinsic Josephson junctions in a high-T-c superconducting Bi2Sr2CaCu2O8+delta single crystal, we embedded a rectangular stand-alone mesa of that material in a sandwich structure to allow for efficient heat exhaust. By varying the current-voltage (I-V) bias conditions and the bath temperature T-b, f is tunable from 0.3 to 1.6 THz. The maximum P of a few tens of mu W, an order of magnitude greater than from previous devices, was found at T-b similar to 55K on an inner I-V branch at the TM(1,0) cavity resonance mode frequency. The highest f of 1.6 THz was found at T-b = 10K on an inner I-V branch, but away from cavity resonance frequencies. A possible explanation is presented

Squamous Cell Carcinoma of the Scalp after Artificial Hair Implantation

A 48-year-old man with a protruding tumor on the parietal region had undergone treatment of alopecia using artificial synthetic fibers 2 or 3 times a year for 10 years from 30 to 39 years old. Three months before the first consultation at our hospital, he noticed a small tumor that had gradually shown bleeding and discharge, with expansion of the affected area. A diagnosis of squamous cell carcinoma (SCC) was made based on a biopsy, and we resected the tumor with a 1-cm surgical margin from the reddened area around the protruding tumor (14 × 11 cm), including the periosteum membrane. No tight adhesion was found between the periosteum and skull, so we excised the outer table of the skull of the central part (diameter: 8 cm) for a pathological analysis. A pathological study showed moderately differentiated SCC with a negative surgical margin. The whole tumor was surrounded by scar tissue with buried artificial hair implants. The second surgery was performed on the 15th postoperative day. An anterolateral thigh flap was divided into 2 flaps to fit the circle-shaped wound. This is the second report of SCC developing after artificial hair implantation in the frontal-parietal scalp. The whole protruding tumor was surrounded by scar tissue with buried artificial hair implants. Proving the direct causal relationship between inflammation of scar tissue and SCC generation is difficult; however, our pathological findings support the possibility of the harmful effects of artificial hair implants

A case of Langerhans cell sarcoma on the scalp: Whole‐exome sequencing reveals a role of ultraviolet in the pathogenesis

Langerhans cell sarcoma (LCS) is a high‐grade neoplasm with overtly malignant cytological features and a Langerhans cell phenotype. The underlying genetic features are poorly understood, and only a few alterations, such as those of the MARK pathway‐related genes, CDKN2A and TP53 have been reported. Here we present a 70‐year‐old male with LCS on the scalp and pulmonary metastasis. The multinodular tumor, 3.0 cm in diameter, consisted of diffusely proliferated pleomorphic cells with numerous mitoses (53/10 HPFs). Immunohistochemically, the tumor cells were positive for CD1a, Langerin and PD‐L1, and the Ki‐67 labeling index was 50%. These pathological features were consistent with LCS, and were also observed in the metastatic tumor. Whole‐exome sequencing revealed that both the primary and metastatic tumors harbored a large number of mutations (>20 mutations/megabase), with deletion of CDKN2A and TP53 mutation, and highlighted that the mutational signature was predominantly characteristic of ultraviolet (UV) exposure (W = 0.828). Our results suggest, for the first time, that DNA damage by UV could accumulate in Langerhans cells and play a role in the pathogenesis of LCS. The high mutational burden and PD‐L1 expression in the tumor would provide a rationale for the use of immune checkpoint inhibitors for treatment of unresectable LCS

DELAY OF GERMINATION 1-LIKE 4 acts as an inducer of seed reserve accumulation

More than 70% of global food supply depends on seeds. The major seed reserves, such as proteins, lipids, and polysaccharides, are produced during seed maturation. Here, we report that DELAY OF GERMINATION 1-LIKE 4 (DOGL4) is a major inducer of reserve accumulation during seed maturation. The DOGL family proteins are plant-specific proteins of largely unknown biochemical function. DOGL4 shares only limited homology in amino acid sequence with DOG1, a major regulator of seed dormancy. DOGL4 was identified as one of the outstanding abscisic acid (ABA)-induced genes in our RNA sequencing analysis, whereas DOG1 was not induced by ABA. Induction of DOGL4 caused the expression of 70 seed maturation-specific genes, even in germinating seeds, including the major seed reserves ALBUMIN, CRUCIFERIN and OLEOSIN. Although DOG1 affects the expression of many seed maturation genes, the major seed reserve genes induced by DOGL4 are not altered by the dog1 mutation. Furthermore, the reduced dormancy and longevity phenotypes observed in the dog1 seeds were not observed in the dogl4 mutants, suggesting that these two genes have limited functional overlap. Taken together, these results suggest that DOGL4 is a central factor mediating reserve accumulation in seeds, and that the two DOG1 family proteins have diverged over the course of evolution into independent regulators of seed maturation, but retain some overlapping function.</p