The potential value of thallium-201 scintigraphy in the diagnosis of squamous cell carcinoma arising from extensive pyoderma.

Squamous cell carcinoma (SCC) arises from a variety of premalignant conditions, including pyoderma. However, an accurate diagnosis of SCC is sometimes challenging due to indistinguishable inflammatory lesions. Here, we present a case of SCC arising from extensive pyoderma, which was successfully diagnosed by taking advantage of thallium-201 scintigraphy. A 49-year-old man presented with an elevated tumor on his right buttock. Computed tomography (CT) and enhanced magnetic resonance imaging (MRI) identified the tumor, but many indistinguishable lesions were also found around the tumor. Histopathology revealed an atypical proliferation of keratinocytes with cancer pearls inside the tumor nests, while histopathology of nodules around the tumor revealed inflammatory tissues. Positron emission tomography CT (PET/CT) revealed an accumulation of 2-deoxy-2-[18 F]-D-glucose at the axillae and inguinal nodes, and at subcutaneous tissues in addition to the tumor. From the CT, enhanced MRI, and PET/CT analyses it was impossible to differentiate many scattered subcutaneous nodules on the trunk from SCCs. However, thallium-201 scintigraphy identified only the tumor and found no accumulation in other nodules. This finding suggests that thallium-201 scintigraphy is useful for the diagnosis of SCC by excluding false-positive signals detected by other imaging technologies.

Immunohistochemical Differentiation between Western and East Asian Types of CagA-Positive Helicobacter pylori in Gastric Biopsy Samples.

Background: Cag A-positive Helicobacter pylori isolated from human gastric mucosa is categorized as a Western or East Asian allele-type based on whether the cagA gene encodes an EPIYA-C or EPIYA-D motif. We aimed to differentiate between the 2 types of H. pylori by immunohistochemistry (IHC) using formalin-fixed paraffin-embedded (FFPE) gastric biopsy samples. Materials and Methods: We developed 2 monoclonal antibodies (mAbs) that detect either the EPIYA-C or EPIYA-D motif of the H. pylori CagA protein by IHC using FFPE tissues. FFPE tissue sections from 30 Japanese and 39 Brazilian gastric biopsy samples with H. pylori infection confirmed by Giemsa staining (moderate/severe in the Sydney classification system) were examined by IHC with the novel mAbs followed by polymerase chain reaction (PCR) for EPIYA-C or EPIYA-D using DNA extracted from adjacent tissue sections. Results: Differentiation among Western and East Asian types and CagA-negative H. pylori was successful in most (97%) samples by IHC with the novel mAbs and commercially available mAbs that react with a species-specific lipopolysaccharide or a common CagA motif of H. pylori. The detection status of EPIYA-C/D motifs by IHC with the novel mAbs was consistent with the PCR results in 61 (88%) of 69 samples: EPIYA-C(+)/D(-) in zero Japanese and 26 Brazilian samples, EPIYA-C(-)/D(+) in 26 Japanese and 1 Brazilian sample, and EPIYA-C(-)/D(-) in 1 Japanese and 7 Brazilian samples. The detection sensitivity and specificity of IHC with each novel mAb compared with the PCR results were, respectively, 84% and 97% for EPIYA-C, and 97% and 95% for EPIYA-D. Conclusions: The novel mAbs specific to each EPIYA-C or EPIYA-D motif differentiated between Western and East Asian types of CagA-positive H. pylori by IHC using FFPE tissues. Applying these novel mAbs to large numbers of archived pathology samples will contribute to elucidating the association of these allele types with gastric cancer.

PHOX2B is a Sensitive and Specific Marker for the Histopathological Diagnosis of Pheochromocytoma and Paraganglioma.

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are non-epithelial neuroendocrine neoplasms originating from the adrenal medulla and paraganglion of the sympathetic and parasympathetic nervous system, respectively. PCCs and PGLs show histological similarities with other epithelial neuroendocrine neoplasms and olfactory neuroblastomas (ONBs), and the differential diagnosis of PGLs is particularly difficult. Therefore, we compared the sensitivity of PHOX2A, PHOX2B, and tyrosine hydroxylase (TH) in the histopathological diagnosis of PCCs and PGLs immunohistochemically using the tissue microarrays of 297 neoplasms including PCCs, PGLs, neuroblastomas, ganglioneuromas, epithelial neuroendocrine neoplasms, and ONBs. Using cutoff values of 25%, 5%, and 5% of tumor cells expressing PHOX2A, PHOX2B, and TH, respectively, as positive, 40 of 51 PCCs, 32 of 33 parasympathetic/head and neck PGLs (HNPGLs), 17 of 19 sympathetic/thoracoabdominal PGLs (TAPGLs), and 12 of 152 epithelial neuroendocrine neoplasms, including 123 well-differentiated and 29 poorly differentiated neuroendocrine neoplasms, were PHOX2A-positive. All 51 PCCs, 33 HNPGLs, and 19 TAPGLs were PHOX2B-positive, while all 152 epithelial neuroendocrine neoplasms were PHOX2B-negative. Moreover, 50 of 51 PCCs, 13 of 33 HNPGLs, all TAPGLs, and 12 of 152 epithelial neuroendocrine neoplasms were TH-positive. All ONBs were negative for PHOX2A, PHOX2B, and TH. PHOX2B was the most sensitive and specific diagnostic marker for PCCs and PGLs among PHOX2A, PHOX2B, and TH. PHOX2B can facilitate identification of PCCs and PGLs from epithelial neuroendocrine neoplasms and ONBs, especially in the case of HNPGLs, in which TH is often negative.

Categorization of cutaneous epithelioid angiomatous nodule as epithelioid hemangioma or angiolymphoid hyperplasia with eosinophilia: Clinicopathologic, immunohistochemical, and molecular analyses of seven lesions.

BACKGROUND: The status of cutaneous epithelioid angiomatous nodule (CEAN) as a distinct entity remains controversial. This study investigated the relationship between CEAN and epithelioid hemangioma/angiolymphoid hyperplasia with eosinophilia (ALHE). METHODS: Data of seven lesions with CEAN features from four cases (Cases 1-4: 61-year-old, 76-year-old, 53-year-old, and 21-year-old men, respectively) were investigated. RESULTS: Cases 1 and 2 showed multiple lesions in the head and neck region, but Cases 3 and 4 showed solitary lesions on the back and scalp, respectively. Moreover, the histopathologic findings of the lesions of Cases 1 and 2 were consistent with those of conventional epithelioid hemangioma or classic cutaneous ALHE. Diffuse immunoexpression of FOSB was observed in Cases 1 and 2, but FOSB split signals were absent in break-apart fluorescence in situ hybridization (FISH). In contrast, the histopathologic findings of the lesions of Cases 3 and 4 were consistent with those of cellular-type epithelioid hemangiomas. Diffuse immunoreactivity for c-FOS was observed in Cases 3 and 4, and split signals of FOS were present in break-apart FISH in Case 3. CONCLUSIONS: This study showed that the seven tumors with CEAN features could be reclassified under the epithelioid hemangioma/ALHE group, although the small sample size is a limitation.

Co-existence of BRAF V600E-mutated malignant melanoma and BRAF V600E-mutated Langerhans cell histiocytosis: A case report.

Langerhans cell histiocytosis (LCH) is a neoplastic condition of Langerhans cells, and can be associated with other neoplasms, especially BRAF-mutant hematological tumors and papillary thyroid carcinoma. Here we present the first case of co-existing LCH and low cumulative sun damage (low-CSD) melanoma, both of which had a BRAF V600E mutation. A 49-year-old man had a 45 × 43 × 15 mm semi-pedunculated, pigmented tumor in his back but had no other systemic symptoms. Histopathology revealed a 2-mm-sized incidental focus of LCH within a large lesion of low-CSD melanoma. Diffuse immunoexpression of CD1a, langerin/CD207, S100 protein, and BRAF (VE1) was observed in the focus of LCH. Sanger sequencing with microdissection confirmed BRAF V600E mutation in the component of LCH. Interestingly, the advanced melanoma also harbored the same BRAF V600E mutation, although the significance of this tumor combination is still unknown.

18F-FDG-Detected Brown Tumor Confined to the Maxillary Bone With Parathyroid Adenoma.

ABSTRACT: Brown tumor is a reactive osteolytic lesion associated with hyperparathyroidism and an extremely rare form of a single lesion in the maxilla. We report the case of a 57-year-old woman with renal dysfunction, nasal obstruction, and hypercalcemia. MRI and CT revealed a huge osteolytic lesion in the maxilla. 18F-FDG PET/CT demonstrated marked FDG uptake within the mass and the lower-left lobe of the thyroid gland. 99mTc-methoxy-isobutyl-isonitrile scintigraphy suggested that this accumulation was a parathyroid adenoma. Parathyroid adenoma resection was performed, and the maxillary tumor was diagnosed as brown tumor. FDG PET/CT was helpful in evaluating brown tumor and detecting parathyroid adenoma.

Propionibacterium acnes-Derived Circulating Immune Complexes in Sarcoidosis Patients.

Propionibacterium acnes is a potential etiologic agent of sarcoidosis and a dysregulated immune response to the commensal bacterium is suspected to cause granuloma formation. P. acnes-derived insoluble immune complexes were recently demonstrated in sinus macrophages of sarcoidosis lymph nodes, suggesting local proliferation of the bacterium in affected organs. In the present study, we developed a method for detecting P. acnes-derived immune complexes in human blood by measuring the concentration of P. acnes-specific lipoteichoic acid (PLTA) detectable after an antigen retrieval pretreatment of plasma samples. Before pretreatment, anti-PLTA antibody was detected and PLTA could not be detected, in all plasma samples from 51 sarcoidosis patients and 35 healthy volunteers. After pretreatment, however, a significant level of PLTA (>105 ng/mL) was detected in 33 (65%) sarcoidosis patients and 5 (14%) control subjects, with 86% specificity and 65% sensitivity for sarcoidosis. In both groups, plasma anti-PLTA antibody titers did not differ between samples with and without detection of PLTA. PLTA levels were abnormally increased (>202 ng/mL) in 21 (41%) sarcoidosis patients. These findings suggest that P. acnes-derived circulating immune complexes present in human blood are abnormally increased in many sarcoidosis patients, presumably due to local proliferation of the bacterium in the affected organs.

Stem cell spreading dynamics intrinsically differentiate acral melanomas from nevi.

Early differential diagnosis between malignant and benign tumors and their underlying intrinsic differences are the most critical issues for life-threatening cancers. To study whether human acral melanomas, deadly cancers that occur on non-hair-bearing skin, have distinct origins that underlie their invasive capability, we develop fate-tracing technologies of melanocyte stem cells in sweat glands (glandular McSCs) and in melanoma models in mice and compare the cellular dynamics with human melanoma. Herein, we report that glandular McSCs self-renew to expand their migratory progeny in response to genotoxic stress and trauma to generate invasive melanomas in mice that mimic human acral melanomas. The analysis of melanocytic lesions in human volar skin reveals that genetically unstable McSCs expand in sweat glands and in the surrounding epidermis in melanomas but not in nevi. The detection of such cell spreading dynamics provides an innovative method for an early differential diagnosis of acral melanomas from nevi.

Supraclavicular Scrofuloderma: A Diagnostic Challenge without Apparent Clinical Manifestations of Tuberculosis.

Scrofuloderma is one of the cutaneous manifestations of tuberculosis and usually occurs when underlying tuberculosis such as lymphadenitis directly involves the skin. However, the diagnosis of scrofuloderma without other apparent clinical manifestations of tuberculosis is sometimes challenging. A 27-year-old male from Bangladesh presented with a dome-shaped tumor on his right clavicle. MRI showed a high-density area that expanded from the lymph nodes between the internal jugular vein and the common carotid artery into the tumor on his right clavicle. Bacterial examinations of cultures from the tumor detected Mycobacterium tuberculosis. Further examinations for pulmonary tuberculosis including chest X-ray and computed tomography did not detect any lesions suggestive of pulmonary tuberculosis. From those examinations, the diagnosis of scrofuloderma was made. We emphasize the importance of recognizing a variety of clinical manifestations of tuberculosis including scrofuloderma due to the recent increase of immigrants from developing countries.