Red Nodule on the Breast

This case report describes an interesting example of a syringocystadenoma papilliferum lesion presenting in a 72-year-old man. He presented with a 10-month history of a red nodule in his umbilicus with unexplained weight loss and reduced appetite. The patient had a background of chronic obstructive pulmonary disease, treated prostate cancer and pemphigus vulgaris that had previously been treated with azathioprine. The nodule would occasionally bleed with trauma, but there were otherwise no associated symptoms. Physical examination revealed a 12 × 12 mm firm red nodule within the umbilicus with some creamy exudate overlying it. Given the clinical presentation, differentials at the time included Sister Mary Joseph nodule, amelanotic melanoma and pyogenic granuloma. A shave biopsy was arranged to help diagnose the nodule and further investigations including computed tomography (CT) and colonoscopy were undertaken. CT and colonoscopy did not indicate any sinister pathology. Histopathological findings demonstrated mildly cystic invaginations arising from a papillomatous epidermis that were lined by rows of cuboidal-to-columnar epithelial cells, with oval nuclei and a pale eosinophilic cytoplasm with squamous metaplasia. The stroma contained a dense mononuclear infiltrate, which was comprised predominantly of plasma cells and lymphocytes. The histopathological findings were of syringocystadenoma papilliferum. This report discusses the clinical and histopathologicial presentation of syringocystadenoma papilliferum and the investigations and management to consider with this diagnosis. We also discuss the various differentials that should be considered for a red nodule in the umbilicus.

Sandgren EP, Palmiter RD, Heckel JL, Daugherty CC, Brinster RL, Degen JL. Complete hepatic regeneration after somatic deletion of an albumin–plasminogen activator transgene [Cell 1991;66:245–256

To the Editor: A 72-year-old woman underwent radical excision of an adenocarcinoma of the right nasolacrimal duct. Postoperative radiation therapy (30 Gy) was added to the residual tumor, which, however, it was insufficient, and the tumor persisted at the external base of the skull. During admission, she was referred to our department complaining of a nodule on the abdomen. Physical examination showed a 5-mm-sized reddish nodule with erosion of the surface (Fig. 1A). A skin biopsy showed tumor nests connecting to the epidermis and extending downwards into the dermis (Fig. 1B). High-power magnification revealed small uniformly cuboidal cells with round deeply basophilic nuclei, which were connected by intercellular bridges. A few cystic or ductal structures were identified within the nests. Immunohistological examination showed strong expression of carcinoembryonic acid in the duct wall, and poroid cells were positive for epithelial membrane antigen. Gross cystic disease fluid protein-15 (GCDFP-15) was negative. Further clinical examination revealed additional reddish nodules on the trunk, neck, and extremities (Figs. 2A, B), which summed up to 10 in total. She complained that those nodules were increased in number after radiation therapy. All of them were surgically removed under local anesthesia. Histological examination revealed that all of them were compatible with the features of poroma. Histological examination showed anastomosing lobules of nests consisting of small, uniform, basophilic, and cuboidal poroid cells. Scattered ductal structures surrounded by the eosinophilic cuticular cells were also recognized. Notably, some of the poromas showed that the tumor nests were confined to the epidermis, indicating intraepidermal poroma (Fig. 2C). In contrast, others were those of Pinkus type. The tumor nests were surrounded with myxomatous stroma, which were highlighted by Alcian blue stain (Fig. 2D). Findings of peripheral palisading were absent in all the basophilic tumor islands.FIGURE 1: A reddish nodule on the chest (arrow). A, Surrounding erythema is allergic contact dermatitis due to adhesive tape. B, Histological features showing anastomosing lobules of tumor nests consisting of poroid cells.FIGURE 2: A and B, Reddish small nodules are scattered on the chest, neck, shoulders, and other areas on the trunk. C, Tumor nests were confined within the epidermis in some lesions. D, Tumor nests in the dermis were surrounded by myxomatous stroma, which was positively stained by Alcian blue stain.The most interesting feature in our case is the multiple occurrences of poromas after radiation therapy in a cancer-bearing patient. Poroma usually occurs as a solitary lesion or at most a few lesions. So far, several cases of multiple eccrine poromas have been reported, most of them occurred in patients with malignancies (Table 1).2–7 In particular, hematologic malignancies such as lymphoma or leukemia have been seen.6,7 In other cases, poromas arised on the irradiated sites5–7 or occur following chemotherapies.7 Our case rapidly developed multiple poromas after radiation therapy, although the occurrence sites were not the irradiated sites. In addition to hematologic malignancies, there also reports of poromas developing after bone marrow transplantation and subsequent graft versus host disease.7 Our case presented with not hematologic malignancy but invasive solid cancer. There was no evidence of either lymph node or distant metastases. The development of multiple poromas may be secondary to immunosupression.TABLE 1: Multiple Eccrine PoromasAnother interesting point was that the poromas exhibited different histological patterns, although presented similar clinical features. Some of them showed the features of common Pinkus type, while the others showed intraepithelial nests, namely intraepidermal poromas. The behavior of all the resected poromas was benign. Additionally, the stroma surrounding the poroma nests was myxomatous in some of the lesions showing mucin deposition which was highlighted by Alcian blue stain. Mucinous stroma is not a common finding in poromas. In conclusion, we report a case of multiple poromas in a patient with invasive carcinoma. The patient was not treated with chemotherapy, but eruptive poromas occurred after radiation therapy. The occurrence of multiple poromas may be related to immunosupression.

Merkel cell carcinomas are rare tumors of the skin with an aggressive behavior and frequent regional and distant metastases. Typically, the primary is a fast-growing, painless, reddish nodule with an iceberg-like effect, broadening in the depth. On the trunk and the buttocks, deep clinically rather inconspicuous nodules can occur. The clinical differential diagnosis of the Merkel cell carcinoma includes skin metastases, malignant lymphomas, malignant adnexal tumors and cysts when the tumor is located deep in the soft tissue (e.g. on the buttocks). Histological and immunohistochemical analysis is necessary for the diagnosis. The demonstration of cytokeratin 20 in the typical globular distribution pattern is of main importance in the diagnosis of Merkel cell carcinoma. Because they are very rare, Merkel cell carcinomas are infrequently diagnosed clinically, in spite of the rather characteristic picture. Diagnostic excision with a safety margin of 3 cm is recommended followed by an adjuvant radiotherapy. The radiation field should include the area of the draining vessels and the first regional lymph nodes. There are some reports concerning the advantage of sentinel lymph node biopsy. In distant metastases, the therapy is multimodal and palliative including surgery, radiation and chemotherapy. Because of the high incidence of regional and distant metastases, regular follow-up is important.

BackgroundMerkel cell carcinoma (MCC) is a kind of cutaneous neuroendocrine cancer with a poor prognosis. It is characterized by a high rate of recurrence and metastases, including distant metastases and regional nodal metastases. Clinically, MCC often manifests as obvious single painless hard nodules visible in sun irradiation of diameter <2 cm and not uncommonly >2 cm, with rapid growth and metastases, especially lymph node metastases. Due to the aspecific nature of MCC, it is often confused with other skin cancers. Exploring different treatments of MCC is necessary.Case presentationThe current study describes the case of an 86-year-old retired man, who presented with a 2.5×2.0×1.2 cm red nodule on the right thigh, which was initially diagnosed as subcutaneous small cell cancer. Upon histological and immunohistochemical analysis, the tumor was consistent with a diagnosis of MCC.ResultsAntiangiogenic therapy combining endostar and apatinib was administered and a partial response achieved after 2.0 months of treatment, and 6.5 months of progression-free survival was achieved. Overall survival was 13.0 months.ConclusionWe believe that antiangiogenic therapy is an extremely effective treatment for MCC, especially for patients who cannot tolerate chemotherapy and radiotherapy.

Recent studies have analysed the impact of Merkel cell polyomavirus (MCPyV) on the clinical features and prognosis of patients with Merkel cell carcinoma (MCC). However, there are currently no available data on specific morphological clinical differences of MCC according to MCPyV-positive (MCPyV+) and -negative (MCPyV-) status and any possible prognostic implications of the different clinical presentations. To describe the clinicopathological characteristics of patients with MCC and the prevalence of MCPyV infection in an Italian cohort of patients and to define possible differences in clinicopathological and prognostic features among MCPyV+ and MCPyV- MCCs. A retrospective, multicentre cohort study was conducted in two Italian tertiary referral centres. MCPyV presence was detected by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) with two different primer sets, amplifying the viral protein (VP1) or large T antigen (LT) viral regions (VP1-PCR and LT-PCR, respectively). Clinicopathological features were compared between MCPyV+ and MCPyV- tumours and between red exophytic nodules and subcutaneous cyst-like MCCs. Of the 62 MCCs that were included, 43 (69%) presented as red exophytic nodules and 12 (19%) with a subcutaneous cyst-like appearance; MCPyV was detected in 25 cases (40%) by IHC, 35 (56%) by VP1-PCR and 49 (79%) by LT-PCR. No correlation was found between clinical morphology and viral status. Mortality rate was higher for MCPyV- cases (77%) than for MCPyV+ (23%) (P = 0.239) and higher for red nodules (70%) than for cyst-like lesions (59%) (P = 0.005). By multivariable analysis, age at diagnosis, Ki67 proliferation index and treatment with surgery/radiotherapy remained the only factors significantly affecting overall survival. This study highlights the potential impact of clinical morphology of MCCs on prognosis. Subcutaneous cyst-like morphology may provide a survival benefit to the patients, regardless of MCPyV status.

Pituitary Ependymoma: A Case Report and Review of the Literature.

ABSTRACTObjectivesThe primary objective of this study is to report and analyze two rare cases of secretory carcinoma (SC) of the minor salivary glands, focusing on their diagnostic and therapeutic work‐up. The study aims to enhance scientific knowledge about SC, which is crucial for developing targeted therapies and ensuring precise diagnosis, especially differentiating it from acinic cell carcinoma (ACC).Materials and MethodsThe study involved a detailed examination of two patients diagnosed with SC of the minor salivary glands. Clinical examinations, histological investigations, and immunohistochemical analyses were conducted. The treatment approach included surgical excision of the lesions followed by regular follow‐ups to monitor for recurrence. Immunohistochemical analysis was performed to identify the presence of markers such as GATA3, SOX‐10, NTRK, mammaglobin, and others.ResultsTwo cases are shown: a case of a 76‐year‐old male with a lesion in the hard palate was initially misdiagnosed as leukoplakia. After surgical excision and histological examination, the lesion was identified as SC. The patient underwent follow‐up examinations, including MRI and CT scans, which showed no recurrence, and another case of a 39‐year‐old female with a nodule in the superior left vestibule underwent surgery to remove the nodule. Histological and immunohistochemical analyses confirmed SC, showing a high proliferation index and presence of the ETV6–NTRK3 gene fusion. Follow‐up imaging showed no signs of disease recurrence.ConclusionsThe study underscores the importance of precise diagnosis and differentiation of SC from ACC. Surgical excision followed by regular monitoring is effective in managing SC. Immunohistochemical and molecular analyses are crucial for accurate diagnosis. The findings contribute to the growing body of evidence on SC and highlight the potential for developing more targeted therapies. Further research is needed to establish clear guidelines for follow‐up duration and treatment protocols.

Rhabdomyomatous mesenchymal hamartoma presenting as a skin tag in a newborn

BACKGROUND AND AIM: Benign fibrous histiocytoma (BFH) is a rare lesion in the head and neck with a slow, single, and painless growth that consists of fibroblasts and histiocytes. In this study, a BFH case was reported and examined from clinical, microscopic, and immunohistochemical aspects. CASE REPORT: A 36-year-old man with a red nodule on the dorsal surface of his tonguewas referred to the oral medicine department. The appearance of this nodule was similar to the adjacent tissue in its surface. According to the same microscopic view of this lesion with other soft tissue tumors, immunohistochemistry test confirmed the diagnosis. It was treated with en-bloc surgical resection. In four follow-ups up to one year, there was no recurrence. Considering the results of these cases and comparing them with other cases, although there is a slim chance of recurrence in one year, follow up is recommended. CONCLUSION: Clinical view of FH is not characteristic and tumors with microscopic spindle-shaped appearance are challenging in diagnosis. IHC is obligatory to reach a prompt diagnosis and due to recurrence, follow-up is recommended.

BackgroundRecently, it has been reported that the Gly573Ser substitution of transient receptor potential V3 (TRPV3) leads to increased ion-channel activity in keratinocytes. Our previous studies have indicated that the spontaneous hairless and dermatitis phenotypes of DS-Nh mice, which were newly established as an animal model of atopic dermatitis (AD), are caused by TRPV3Gly573Ser. Although this substitution causes hairlessness in several kinds of rodents, in our investigations, dermatitis developed in only a few animals. Here, we generated NC/Nga-Nh mice to elucidate the role of TRPV3Gly573Ser in NC/Nga mice, which is one of the most studied animal models of AD.MethodsTo establish and validate the new AD animal model, NC/Nga-Nh mice were generated using NC/Nga and DS-Nh mice, and their clinical features were compared. Next, T-cell receptor (TCR) Vβ usage in splenocytes, evaluation of bacterial colonization, and serological and histological analyses were carried out. Finally, repeated-hapten-application dermatitis was induced in these mice.ResultsNC/Nga-Nh mice did not develop spontaneous dermatitis, whereas DS-Nh mice displayed this phenotype when maintained under the same conditions. Serological analysis indicated that there really was a phenotypic difference between these mice, and TCR repertoire analysis indicated that TCRVβ haplotypes played an important role in the development of dermatitis. Artificial dermatitis developed in DS and NC/Nga-Nh mice, but not in DS-Nh and NC/Nga mice. Histological and serological analyses indicated that mouse strains were listed in descending order of number of skin mast cells: DS-Nh > DS ≈ NC/Nga-Nh > NC/Nga, and serum IgE levels were increased after 2,4,6 trinitrochlorobenzene application in these mice. Serum IgE level in DS-Nh mice was lower than that mesured in other strains.ConclusionOur results confirm the contribution of the TRPV3Gly573Ser gene to the development of repeated hapten dermatitis, but not spontaneous dermatitis in NC/Nga mice.

BackgroundOssification of the posterior longitudinal ligament (OPLL), an emerging heterotopic ossification disease, causes spinal cord compression, resulting in motor and sensory dysfunction. The etiology of OPLL remains unclear but may involve integrin αVβ3 regulating the process of osteogenesis and angiogenesis. In this study, we focused on the role of integrin αVβ3 in OPLL and explored the underlying mechanism by which the c(RGDyk) peptide acts as a potent and selective integrin αVβ3 inhibitor to inhibit osteogenesis and angiogenesis in OPLL.MethodsOPLL or control ligament samples were collected in surgery. For OPLL samples, RNA-sequencing results revealed activation of the integrin family, particularly integrin αVβ3. Integrin αVβ3 expression was detected by qPCR, Western blotting, and immunohistochemical analysis. Fluorescence microscopy was used to observe the targeted inhibition of integrin αVβ3 by the c(RGDyk) peptide on ligaments fibroblasts (LFs) derived from patients with OPLL and endothelial cells (ECs). The effect of c(RGDyk) peptide on the ossification of pathogenic LFs was detected using qPCR, Western blotting. Alkaline phosphatase staining or alizarin red staining were used to test the osteogenic capability. The effect of the c(RGDyk) peptide on angiogenesis was determined by EC migration and tube formation assays. The effects of the c(RGDyk) peptide on heterotopic bone formation were evaluated by micro-CT, histological, immunohistochemical, and immunofluorescence analysis in vivo.ResultsThe results indicated that after being treated with c(RGDyk), the osteogenic differentiation of LFs was significantly decreased. Moreover, the c(RGDyk) peptide inhibited the migration of ECs and thus prevented the nutritional support required for osteogenesis. Furthermore, the c(RGDyk) peptide inhibited ectopic bone formation in mice. Mechanistic analysis revealed that c(RGDyk) peptide could inhibit osteogenesis and angiogenesis in OPLL by targeting integrin αVβ3 and regulating the FAK/ERK pathway.ConclusionsTherefore, the integrin αVβ3 appears to be an emerging therapeutic target for OPLL, and the c(RGDyk) peptide has dual inhibitory effects that may be valuable for the new therapeutic strategy of OPLL.

Introduction/BackgroundSerous Tubal Intraepithelial Carcinoma (STIC) is considered the main precursor of high-grade serous carcinoma (HGSC). There are no standardized diagnostic criteria; an algorithm combining histological and immunohistochemical (IHC) analysis has...

The 2021 WHO Classification of Tumors of the Heart

While porcine circovirus 2 (PCV2) was first identified in sporadic cases of postweaning multisystemic wasting syndrome in Canada in the early 1990s, an epidemic of severe systemic disease due to PCV2 spread worldwide in the ensuing decade. Despite being effectively controlled by commercial vaccines, PCV2 remains one of the most economically significant viruses of swine. Here, a novel porcine circovirus (PCV3) that is distantly related to known circoviruses was identified in sows with porcine dermatitis and nephropathy syndrome (PDNS) and reproductive failure. PCV2, which has previously been associated with these clinical presentations, was not identified. High levels of PCV3 nucleic acid were observed in aborted fetuses by quantitative PCR, and PCV3 antigen was localized in histologic lesions typical of PDNS in sows by immunohistochemistry (IHC) analysis. PCV3 was also identified in archival PDNS diagnostic samples that previously tested negative for PCV2 by IHC analysis. The emergence of PCV3 warrants further investigation.