Haruto Nishida

KIT (CD117) Expression in Benign and Malignant Sweat Gland Tumors.

Abstract:KIT (CD117, c-kit) is a receptor tyrosine kinase involved in the tumorigenesis of several neoplasms. KIT is expressed by the secretory cells of normal sweat glands. We studied the KIT expression and KIT mutational status in various benign and malignant tumors of eccrine and apocrine glands. We included a total of 108 cases comprising 10 benign and 6 malignant sweat gland tumors, and KIT expression was immunohistochemically detected (positive rate): 10 syringomas (0%), 8 poromas (25%), 20 mixed tumors (40%), 21 spiradenomas (43%), 1 cylindroma (0%), 5 hidradenomas (40%), 7 syringocystadenoma papilliferum cases (0%), 1 papillary hidradenoma (100%), 2 tubulopapillary hidradenomas (50%), 8 hidrocystomas (29%), 2 adenoid cystic carcinomas (100%), 5 porocarcinomas (20%), 6 apocrine carcinomas (33%), 10 extramammary Paget diseases (30%), 1 spiradenocarcinoma (100%), and 1 syringocystadenocarcinoma papilliferum (0%). Most KIT-positive cells were luminal cells, arising from glandular structures. We performed polymerase chain reaction–single-strand conformation polymorphism for detecting KIT mutational status. All cases showed no mutations at hot spots for KIT (exons 9, 11, 13, and 17). KIT mutation does not seem to be mechanism for KIT expression, but the expression may be from native sweat glands.

Combined large-cell neuroendocrine carcinoma and endometrioid adenocarcinoma of the endometrium: A case report and survey of related literature.

Primary large‐cell neuroendocrine carcinoma of the endometrium is extremely rare and has a poor prognosis. This report describes a case of combined large‐cell neuroendocrine carcinoma and endometrioid adenocarcinoma of the endometrium diagnosed as stage IIIA. The patient underwent surgery and chemotherapy and has been well with no evidence of disease for 20 months. The optimal treatment for this rare tumor has not been established. Considering its rarity and variability, it is difficult to establish an evidence‐based therapeutic regimen.

PLAG1 and CYLD do not play a role in the tumorigenesis of adenoid cystic carcinoma.

The pleiomorphic adenoma gene 1 (PLAG1) gene is activated in a subset of pleomorphic adenomas of the salivary gland by gene fusion. Germ‑line mutation in cylindromatosis (CYLD), a tumor suppressor gene, causes familial cylindromatosis and Brook‑Spiegler syndrome. In the present study, aberrations in PLAG1 and CYLD were investigated in adenoid cystic carcinoma (ACC) of the salivary gland. Reverse‑transcription PCR and PCR direct sequencing were performed to detect gene fusion of PLAG1 and mutation of CYLD in 34 ACC tissues. No PLAG1 fusion was detected in ACC. However, silent mutation of CYLD was detected in 2 cases of ACC, but no missense mutation was detected in ACC. These results suggest that PLAG1 and CYLD do not play a role in ACC tumorigenesis.

Gastric lanthanosis (lanthanum deposition) in dialysis patients treated with lanthanum carbonate.

Lanthanum carbonate (LaC) is used to prevent hyperphosphatemia in dialysis patients. It is commonly believed that there is little LaC absorption from the intestines. However, La deposition in the gastric mucosa, which we coined “gastric lanthanosis”, was recently reported. We describe here the clinicopathological features of and a possible mechanism for gastric lanthanosis. This study included 23 patients with definite gastric lanthanosis. We extracted characteristic clinicopathological features of gastric lanthanosis by computed tomography (CT) imaging and endoscopic, histologic, electron‐microscopic, and element analysis examinations. The Helicobacter pylori infection rate in the lanthanosis group was much lower than that among the general population. The clinicopathological features characteristic of gastric lanthanosis were mucosal high‐density linear appearance by CT, reflective bright‐white spots (BWS) by gastroscopy, eosinophilic histiocytes occasionally phagocytizing foreign materials by histology, and numerous electron‐dense particles in the histiocytes. The particles had burr‐like skeletons resembling La crystals. Gastric lanthanosis is an under‐reported, but not a rare lesion. It is characterized by endoscopic BWS and histologic eosinophilic histiocytes in dialysis patients treated with LaC. The proposed mechanism for gastric lanthanosis is that LaC is dissolved by gastric juice, crystallized within the mucosa and is phagocytized by histiocytes.

Pigmented median raphe cyst of the penis.

To the Editor, Median raphe cyst represents a relatively rare cystic lesion on the median raphe, which extends from the urethral meatus to the anus. Since the first report by Mermet in 1895,1 several terminologies, including median raphe cyst, ‘mucoid cyst of penile skin’ and ‘genitoperineal cyst of the medium raphe’ have been used.2 There is a general agreement that median raphe cyst is derived from the urethral mucosa or urethral gland (Littre’s gland).3 It appears commonly in children or adolescents with a mean size of less than 20 mm.4 Rarely, median raphe cyst contains melanin and melanocytes and clinically has a pigmented appearance. Such a cyst is called pigmented median raphe cyst.5 We report herein a case of pigmented median raphe cyst with a review of the literature. A 6-year-old boy presented with a brownish nodule on the ventral aspect of the penis, which had been noticed 5 years previously and increased in size with body growth. On physical examination, the nodule was slightly elevated with a smooth surface and was elliptical in shape, elastic soft and movable, measuring 2 × 8 mm on the median raphe of the penis (Fig. 1). The nodule was resected, and no local recurrence was noted 10 months postoperatively. Microscopic examination of the resected specimen showed a unilocular cyst in the dermis (Fig. 2A). The inner surface of the cyst was smooth and lined by one to several layers of uniform bland cuboidal cells with abundant brown pigment (Fig. 2B). No cells showed decapitation secretion reminiscent of apocrine origin. The brown pigment was melanin, as it stained black by the Fontana–Masson method and bleached by potassium permanganate–oxalic acid solution. Although it was difficult to detect melanocytes with hematoxylin–eosin staining, immunostaining for Melan A/MART-1 by alkaline phosphatase and fast-red highlighted them at the basal layer (Fig. 2C). Fig. 1. A brownish elliptic-shaped nodule on the median raphe (arrows) of the penis.

Significant expression of thyroid transcription factor-1 in pulmonary squamous cell carcinoma detected by SPT24 monoclonal antibody and CSA-II system.

In contrast to the usefulness of thyroid transcription factor-1 (TTF-1) in distinguishing primary adenocarcinoma of the lung from metastatic lesions, TTF-1 expression in pulmonary squamous cell carcinoma is reported to be at low level and not a suitable immunohistochemical marker. We hypothesized that the highly sensitive detection system, CSA-II, can visualize even faint expression of TTF-1 in pulmonary squamous cell carcinoma. In this study, 2 commercially available clones of TTF-1 monoclonal antibody, 8G7G3/1 and SPT24, were used for staining 38 cases of pulmonary squamous cell carcinoma, in combination with the CSA-II and the conventional detection system, EnVision. The combined use of the 8G7G3/1 clone with EnVision and CSA-II showed a positive reaction in only 1 and 4 cases, respectively. The use of SPT24 clone showed positive staining in 5 cases with EnVision and in 20 of 38 cases (52.6%) with the CSA-II. Interestingly, positive staining by the SPT24-CSA-II technique of samples from tissue blocks preserved for <2 years was 73.6% compared with only 31.5% in those preserved for >2 years. In addition, a 6-month preservation of the cut sections resulted in stain fading and decreased positivity (50%), compared with freshly cut sections. We conclude that the use of the SPT24 monoclonal antibody with the CSA-II system can detect even weak expression of TTF-1 in pulmonary squamous cell carcinoma. This staining technique can potentially allow the discrimination of primary squamous cell carcinoma of the lung from metastatic lesions, especially in freshly prepared paraffin sections.

Cutaneous horn malignant melanoma

A 73-year-old Japanese woman presented with cutaneous horn on the right cheek. The resected tumor was 9 mm in diameter, with 14 mm protrusion, and showed exophytic growth with marked papillomatosis. Histopathology showed proliferation of atypical melanocytes with melanin pigments in the epidermis and dermis under the cutaneous horn. These cells were confined to the base of the cutaneous horn, and did not spread to the surrounding epidermis. The final diagnosis was cutaneous horn malignant melanoma. This pathological entity is considered a specific form of verrucous melanoma, and might be added to the list of cutaneous horn-forming lesions.

The scab-like sign: A CT finding indicative of haemoptysis in patients with chronic pulmonary aspergillosis?

ObjectivesThe aim of this study was to assess the CT findings that characterise haemoptysis in patients with chronic pulmonary aspergillosis (CPA).MethodsWe retrospectively identified 120 consecutive patients with CPA (84 men and 36 women, 17–89 years of age, mean age 68.4 years) who had undergone a total of 829 CT examinations between January 2007 and February 2017. In the 11 patients who underwent surgical resection, CT images were compared with the pathological results.ResultsThe scab-like sign was seen on 142 of the 829 CT scans, specifically, in 87 of the 90 CT scans for haemoptysis and in 55 of the 739 CT scans obtained during therapy evaluation. In 48 of those 55 patients, haemoptysis occurred within 55 days (mean 12.0 days) after the CT scan. In the 687 CT scans with no scab-like sign, there were only three instances of subsequent haemoptysis in the respective patients over the following 6 months. Patients with and without scab-like sign differed significantly in the frequency of haemoptysis occurring after a CT scan (p<0.0001). Pathologically, the scab-like sign corresponded to a fibrinopurulent mass or blood crust.ConclusionsThe scab-like sign should be considered as a CT finding indicative of haemoptysis.Key Points• Haemoptysis is commonly found in patients with CPA.• A CT finding indicative of haemoptysis in CPA patients is described.• Scab-like sign may identify CPA patients at higher risk of haemoptysis.

Case of malignant melanoma that developed the ability to secrete granulocyte colony-stimulating factor.

tory of erosion on her left nipple. Physical examination revealed a reddish nodule measuring 10.7 mm 9 9.8 mm 9 8.0 mm with an erosive surface on her left nipple (Fig. 1a). Breast palpation failed to reveal any masses except for the nodule on her nipple. However, magnetic resonance imaging revealed limited dilation of lactiferous ducts in the upper medial part of her left breast, which was separated from her nipple. A biopsied specimen from her nipple revealed an ill-defined dermal tumor composed of a collection of ductal structures of varying shapes and sizes (Fig. 1b,c). These structures were lined with two distinct types of epithelial cells: myoepithelial cells lining the outer edge of the ductal structure, and cuboidal cells facing the lumen with frequent apocrine snouts. Mild atypia, with variation in size and shape, and hyperchromatic nuclei with prominent nucleoli were observed (Fig. 1c). Immunohistochemically, more than half the tumor cells were positive for 5-hmC (73.0 3.9%) (Fig. 1d). We diagnosed it as EAN and performed a tumor resection with preservation of her left nipple. Mild atypicality was also found in a vacuum-assisted biopsy specimen from the dilated lactiferous ducts. Wide local excision was performed. Histopathologically, mildly atypical epithelial cells formed a cribriform architecture within the ductal structure (Fig. 1e). The ratio of 5-hmC-positive cells was less than 10% (Fig. 1f). We diagnosed it as ductal carcinoma in situ (DCIS). In case 2, a 44-year-old Japanese woman had a 4-month history of bloody discharge from her left nipple. Physical examination revealed a well-defined erosion without induration (Fig. 1g). A biopsied specimen showed ductal structures consisting of two cell types: myoepithelial cells and epithelial luminal cells (Fig. 1h). Immunohistochemically, more than the tumor cells were positive for 5-hmC (83.5 2.9%). We diagnosed it as EAN and performed a tumor resection with preservation of her left nipple. Erosive adenomatosis of the nipple is a benign mammary proliferation that may be misdiagnosed as breast cancer, especially DCIS. DCIS is a malignant proliferation of cells within the basement membrane-bound structures. Immunostaining of several proteins, including carcinoembryonic antigen, vimentin and muscle-specific actin, has been used to aid diagnosis. The results of this staining are reliable, but not absolute. Levels of 5-hmC are dramatically reduced in a broad spectrum of human cancers. Immunohistochemically, fewer than 10% of tumor cells in breast cancer are 5-hmC-positive (Prof. Ken-ichi Ito, 2015, unpubl. data). We noted a clear difference in the proportion of 5-hmC-positive tumor cells between EAN and DCIS, implying that the presence of 5-hmC will be useful for the diagnosis of EAN.

Pemetrexed-induced scleroderma-like conditions in the lower legs of a patient with non-small cell lung carcinoma

Pemetrexed, which is used for the treatment of non‐small cell lung carcinoma and malignant mesothelioma, induces cutaneous adverse reactions in approximately 20% of patients. There are also reports of the induction of fibrosing disorders. We describe a case of pemetrexed‐induced scleroderma‐like conditions in the lower legs of a patient whose pulmonary carcinoma has been relatively well controlled, with prolongation of the dose interval, in spite of the discomfort in both his legs. Skin biopsy revealed dermal fibrosis and dilated lymph vessels in the dermis, but lymphocytic infiltration around the lymph vessels, in contrast to the blood vessels, was minimal. Immunohistochemical staining revealed that the major subsets of T cells that had infiltrated around blood vessels were CD3 and CD45Ro, but no B cells were detected. High serum levels of interleukin (IL)‐4 and IL‐6 suggested that T cells, which secrete these cytokines, may be involved in the pathogenesis of this condition. Magnetic resonance imaging of the lower extremities revealed muscular and fascial involvement. Several chemotherapeutic agents, such as taxanes, gemcitabine and bleomycin, are known to induce scleroderma‐like changes, and we should also keep the side‐effects of pemetrexed in mind when we encounter patients with fibrosing conditions.