Deck-chair sign as a diagnostic clue for insidious T-cell lymphoma: An autopsy case of mycosis fungoides.

Skin reflects the presence of systemic diseases, leading to an unexpected diagnosis of insidious diseases. Deck-chair sign is a unique skin eruption characterized by widespread erythematous papules that become erythrodermic with spare skin folds. An association between the deck-chair sign and malignancies, especially hematological neoplasms, has been suggested. We report a forensic case of mycosis fungoides unexpectedly diagnosed in the presence of a deck-chair sign. Mycosis fungoides is representative of cutaneous T-cell lymphomas. Here, we successfully demonstrated the feasibility of analyzing mycosis fungoides in a forensic autopsy case using basic histopathology and serology. We emphasize that the underlying malignancy should be primarily considered in cadavers with a positive deck-chair sign and review current reports about this characteristic skin manifestation.

Pigmented median raphe cyst of the penis that developed after middle age without infection or trauma history.

INTRODUCTION: Median raphe cysts are rare benign lesions of the male genitalia that can develop anywhere along the midline from meatus to anus. They are believed to be caused by a defect in closure of median raphe during embryonic development. These cysts commonly appear in childhood or adolescence, although some are diagnosed after middle age, typically triggered by infection or trauma. Pigmented median raphe cysts, or those containing melanin pigment and/or melanocytes, are extremely rare. CASE PRESENTATION: A 78-year-old man visited our hospital with a complaint of a penile mass that he first noticed in his 50s which slowly grew, eventually causing voiding difficulty. He had no history of infection or trauma. The lesion was excised, and the pathological diagnosis was pigmented median raphe cyst. CONCLUSION: We successfully treated a rare case of pigmented median raphe cyst of the penis that developed after middle age without infection or trauma history.

Successful Treatment of Mepolizumab- and Prednisolone-resistant Allergic Bronchopulmonary Aspergillosis with Dupilumab.

A 45-year-old man with allergic bronchopulmonary aspergillosis (ABPA) was treated with oral prednisolone (PSL) (30 mg/day), inhaled corticosteroids, and long-acting beta2-agonists. After confirmation of a PSL-dependent status (8 mg/day), subcutaneous injection with anti-interleukin (IL)-5 antibody (mepolizumab, 100 mg/month) was performed, and the PSL dose was tapered to 5 mg/day. However, ABPA recurred and proved refractory to oral itraconazole (200 mg/day). Alternative subcutaneous injection therapy with dupilumab (induction dose of 600 mg followed by a maintenance dose of 300 mg/2 weeks) enabled the successful withdrawal of oral PSL without clinical deterioration. This case demonstrates the potential utility of dupilumab for steroid-dependent ABPA via the synergistic suppression of IL-4 and IL-13 compared to monotherapy with anti-IL-5 antibody.

Membranous nephropathy with masked polyclonal IgG deposits associated with primary Sjögren's syndrome.

Tubulointerstitial nephritis and renal tubular acidosis are well-known renal involvements with primary Sjögren's syndrome. However, several types of glomerulonephritis such as membranoproliferative glomerulonephritis and membranous nephropathy are also known to develop in patients with this syndrome. We here report a case of membranous nephropathy that developed 8 years after a diagnosis of primary Sjögren's syndrome in a female patient. Interestingly, the deposition was not identified by routine immunofluorescence using snap frozen tissue, but was revealed by immunofluorescence on formalin-fixed paraffin-embedded sections treated with proteinase K. We further performed immunofluorescence analysis on the treated paraffin-embedded sections with the identified antigen but found that the deposited IgG was not monoclonal and that serum amyloid P, a sensitive marker for membranous-like glomerulopathy with masked IgG κ deposits, was not evident in the glomeruli. To the best of our knowledge, this report depicted the first case of masked polyclonal IgG deposits and further analysis is needed to clarify the underlying mechanisms of IgG masking and possible association with autoantibodies.

Frontotemporal dermoid cyst with incomplete dermal sinus tract in an adult: A case report.

BACKGROUND: Non-midline supratentorial dermoid cyst with dermal sinus tract has been rarely reported especially in adults. We recently experienced a noteworthy patient with frontotemporal dermoid cyst with incomplete dermal sinus tract. CASE DESCRIPTION: A 43-year-old female presented with recurrent subcutaneous mass in the left superolateral orbital region. She had a history of active bronchial asthma, which precluded her from contrast-enhanced imaging studies. Plain imaging studies showed a subcutaneous mass which was continuous with an intrasylvian fissure mass by a tract in the sphenoid ridge and the lesser wing of the sphenoid bone. Frontotemporal craniotomy was performed to reset the mass and the tract. Intraoperative finding showed no intradural tumor components. Extradural component was carefully removed focusing attention on the frontal branch of the facial nerve. The pathology was consistent with dermoid cyst and dermal sinus tract. Postoperatively, she had mild facial palsy of the corrugator supercilii (House and Brackmann Grade II). She was discharged home with modified Rankin scale 1. CONCLUSION: Dermoid cyst needs to be included in the differential diagnosis of adult-onset subcutaneous mass in the frontotemporal regions. After thorough imaging studies for the presence and extent of the sinus tract, the symptomatic lesion should be excised completely once and for all.

Gastropathy associated with lanthanum phosphate deposition that was endoscopically tracked for 3 years. A case report.

BACKGROUND: With the recent increased use of lanthanum carbonate, several cases of lanthanum phosphate deposition to gastric mucosa in dialysis patients have been reported. However, the endoscopic appearance of the early-stage lesion and the over-time alterations of endoscopic findings due to the progression of lanthanum phosphate deposition remain unclear. CASE PRESENTATION: An 80-year-old man receiving dialysis and taking lanthanum carbonate as a phosphate binder over a 4-year period underwent upper gastrointestinal endoscopy four times beginning 1 year after initiation of treatment. The first endoscopic examination (after 1 year of exposure to lanthanum carbonate) revealed rough mucosa with a few areas of white granular mucosa. Over the 3 years of endoscopic follow-up, the white granular mucosa spread and multiple erosions appeared. Histopathological findings of biopsy specimens from an erosion showed extensive infiltration by histiocytes containing deposits. Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) revealed that the presence of the deposits containing phosphorus and lanthanum in the gastric mucosa. On the basis of these results, the patient was diagnosed with gastropathy associated with lanthanum phosphate deposition. CONCLUSIONS: Over a 3-year period, endoscopic findings associated with lanthanum deposition gradually changed and expanded from the early stage.

Nephrotic syndrome due to minimal-change disease superimposed on anti-glomerular basement membrane antibody positive glomerulonephritis; a case report.

BACKGROUND: The prognosis for renal function in anti-GBM glomerulonephritis (anti-GBM GN) is extremely poor, and when renal impairment progresses severely, it is difficult to expect improvement. In addition, it is also known that once the disease activity can be controlled by aggressive treatment, its recurrence is rare. We experienced an anti-GBM GN that improved from severe renal dysfunction and relapsed. A possible cause was the superimpose of nephrotic syndrome due to minimal change disease (MCD). CASE PRESENTATION: A 30-year-old man was admitted to our hospital because of general malaise, fever, oliguria and renal dysfunction. The patient's laboratory data showed serum creatinine as high as 6.6 mg/dl, and severe inflammation (C-reactive protein 20.6 mg/dl). Anti-glomerular basement membrane antibody (anti-GBM Ab) was detected in his serum, which led to the diagnosis of anti-GBM GN. Treatment was initiated with high-dose glucocorticoid (GC) and plasma exchange therapy (PE), and the patient's renal function and oliguria improved rapidly and he was discharged 40 days after admission. Renal biopsy findings showed cellular crescents associated with linear IgG depositions along the glomerular tufts compatible with anti-GBM GN, but only about one-third of the glomeruli was involved, suggesting that it still remains an early stage of the disease. However, 2 months after discharge, he had a relapse and was readmitted due to severe proteinuria with positive anti-GBM Ab. On the second admission, after high-dose GC and PE combined with intravenous cyclophosphamide, and remission was achieved. Despite the relatively minor renal biopsy findings, the patient showed rapid renal dysfunction and relatively rapid improvement with our treatment. Electron microscopy of the renal biopsy tissue showed significant foot process effacement on podocytes in the apparently normal glomeruli, without electron dense deposits. CONCLUSION: On the basis of clinical course and renal pathology, it is suggested that the present case was a rare complication of an early stage of anti-GBM GN and minimal change nephrotic syndrome. Although the simultaneous development of anti-GBM GN and MCD with anti-GBM antibody is unclear, it might have been precipitated by influenza infection or some unknown factor.

Adult ALCAPA: from histological picture to clinical features.

BACKGROUND: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary anomaly that results in high mortality if left untreated. Our aim was to extend our knowledge of the histological, angiographic, and clinical characteristics of ALCAPA in order to deepen our understanding of this rare entity. CASE PRESENTATION: We were involved in the assessment, treatment, and pathological evaluation of two adult ALCAPA patients who were rescued from ventricular fibrillation and then surgically treated to establish a dual coronary artery system. Histological studies indicated various chronic ischemic changes in the myocardium, patchy fibrosis, and severely thickened arteriolar walls in both ventricles. The first patient is alive and well 11.5 years after surgical correction without any implantable cardioverter defibrillator (ICD) activations. The second patient required re-do surgery 9 months after the initial operation but subsequently died. Histologically, chronic ischemic alteration of the myocardium and thickened arteriolar walls persisted even after surgical correction, and coronary angiography (CAG) showed an extremely slow flow phenomenon even after surgical correction in both patients. The average postoperative opacification rate in the first case was 7.36 + 1.12 (n = 2) in the RCA, 3.81 + 0.51 (n = 3) in the left anterior descending (LAD) artery, and 4.08 + 0.27 (n = 4) in the left circumflex (LCx) artery. The slow flow phenomenon may represent persistent high arteriolar resistance in both ventricles. CONCLUSIONS: Seldom reported or new findings in adult ALCAPA were identified in two cases. More frequent diagnosis of adult ALCAPA can be expected because of the widespread availability of resuscitation and more advanced diagnostic modalities. Accumulation of pathological and clinical findings and confirmation of the long-term follow-up results after treatment may contribute to expanding our knowledge of this rare entity and establishing optimal treatment.

Acute hypotension induced by suction of cystic fluid containing extremely high concentrations of catecholamines during resection of giant pheochromocytoma.

INTRODUCTION: Since pheochromocytomas present with various complications due to catecholamine hypersecretion, their perioperative management needs special attention. CASE PRESENTATION: A 45-year-old man visited our hospital with a complaint of abdominal swelling. Radiological and endocrinological assessments determined the tumor as a giant (>20 cm) cystic pheochromocytoma. After administration of doxazosin, the patient underwent radical surgery. Since the tumor was extremely large and fixed to surrounding structures, we punctured it and aspirated cystic fluid to improve the tumor's mobility. However, during the aspiration, the patient developed acute hypotension, which could be reversed by suction withdrawal and vasopressor administration. A similar event occurred during a second aspiration. Eventually, the tumor was successfully excised with negative surgical margin. The cystic fluid proved to contain extremely high concentrations of catecholamines, which might result in the hypotension. CONCLUSION: We report the first case who developed acute hypotension due to aspiration of cystic fluid from giant pheochromocytoma.

Chronological observation of surgically-treated granuloma faciale implies the necessity of circumspect management for perinasal nodular subset.

Granuloma faciale (GF) is a rare chronic dermatosis with still unknown etiopathology, which usually presents a solitary, asymptomatic, smooth reddish-brown to violaceous plaques or nodules on the face. Various therapeutic approaches, including topical application of corticosteroid or tacrolimus and removal with laser, cryotherapy and surgery have been attempted; however, the outcome has been inconsistent. Herein, we report a case of perinasal nodular GF who repeatedly underwent surgical excisions after the failure of laser treatment. Despite its nomenclature, GF does not manifest granulomatous tissue and the lesion is histopathologically characterized by dense dermal cell infiltration devoid of granulomatous changes and not distinguished by a clear border, which partially explains the difficulty of complete removal in our case. Review of the published work delineated that GF could be largely divided into two clinical subsets: plaque and nodular types. The plaque type GF could be responsive to topical tacrolimus, an approach preferentially adopted nowadays, while nodular type GF was often resistant to topical therapies and required surgical or laser removal. The latter subset often arose around the nose. For this location, surgical excision with sufficient removal margin is sometimes technically difficult when an aesthetically acceptable outcome is expected, explaining the basis for local recurrence. Postoperative recurrence could be observed after years of disease-free period. These observations indicated that the need for respective treatment strategies for the management of distinctive GF subsets. Of note, a multidisciplinary approach combining radical resection and additional supportive intervention with long-term follow up may be required for perinasal and nodular GF.

Altered expression of cytokeratin 7 and CD117 in transitional mucosa adjacent to human colorectal cancer.

The multi-step progression of colorectal cancer through precancerous lesions (adenoma and dysplasia) is associated with cumulative molecular alterations, a number of which have also been demonstrated to be present in morphologically normal transitional mucosa adjacent to colorectal cancer. The cytoskeletal protein cytokeratin 7 (CK7) and the receptor tyrosine kinase, KIT proto-oncogene receptor tyrosine kinase (CD117), encoded by the proto-oncogene c-Kit, are lacking in normal colorectal crypt epithelium and are aberrantly expressed in a subset of colorectal cancer. The aim of the present study was to evaluate the expression of CK7 and CD117 in morphologically normal transitional mucosa adjacent to colorectal cancer. Immunohistochemical staining for CK7 and CD117 was performed in the mucosa adjacent to five groups of surgically resected colorectal tumors [low-grade adenoma, high-grade adenoma, mucosal adenocarcinoma, small-sized invasive adenocarcinoma (≤2 cm) and large-sized invasive adenocarcinoma (>2 cm)]. CK7 was expressed in the mucosa adjacent to a subset of colorectal tumors, and the positivity ratio increased according to tumor grade from low-grade adenoma up to small-sized invasive adenocarcinoma (61.2%). However, the positivity ratio of CK7 in the mucosa adjacent to the large-sized invasive adenocarcinoma (25.0%) was significantly lower compared with that of the next lower grade. CD117 was also expressed in the mucosa adjacent to a subset of colorectal tumors. In contrast to CK7, the positivity ratio of CD117 increased according to tumor grade from low-grade adenoma all the way through to the large-sized invasive adenocarcinoma (45.0%). Based on these results, the mechanism of CK7 and CD117 expression in the transitional mucosa adjacent to colorectal cancer may be different, and analysis of their individual expression may provide novel insights into the development and progression of colorectal cancer.

Pathologic Features of Lone Aortic Mobile Thrombus in the Ascending Aorta.

This report describes the case of a 79-year-old man with aortic mobile thrombus in the ascending aorta, followed by a discussion of the pathologic basis of aortic mobile thrombus formation. The patient underwent replacement of the ascending aorta. Macroscopic examination revealed an aortic wall ulcer with cholesterol-rich atherosclerotic plaque under the aortic mobile thrombus. Microscopic examination showed plaque rupture. These findings are very similar to those of plaque rupture in the coronary artery. We speculate that plaque rupture of localized aortic atherosclerosis is one of the causes of aortic mobile thrombus.

Immaturity of smooth muscle cells in the neointima is associated with acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS) is mostly caused by ruptured plaques. The characteristics of rupture-prone vulnerable plaques include thin fibrous cap, large lipid core, and lower number of smooth muscle cells. Smooth muscle cells appearing in neointimal plaques are currently thought to have a uniformly synthetic phenotype, and their sub-classification has not been performed by h-caldesmon, which is supposed to be expressed in vascular smooth muscle cells that are beyond intermediately differentiated. METHODS: Stenotic coronary arteries were obtained from autopsy material of 51 adults. Cases were divided into three groups: those who died from ACS, those with a past history of ACS but died from other causes, and those without ACS history. Histological data including fibrous cap and lipid core were measured in each specimen. Immunohistochemistry for alpha-smooth muscle actin (α-SMA), h-caldesmon, and smoothelin was performed. The ratio of h-caldesmon(+) cells to α-SMA(+) cells was counted in the neointima. RESULTS: The positivity ratio of neointimal h-caldesmon decreased in a step-wise manner from cases without history of ACS through cases with past history of ACS to cases with ACS with statistical significance (P<.001). The correlation between h-caldesmon expression and progression of ACS among the different groups was more prominent than the differences in the extent of fibrous cap and lipid core. Smoothelin(+) cells were rarely observed in the neointima. CONCLUSIONS: Decreased positivity of h-caldesmon in neointimal smooth muscle cells is indicative of a more immature phenotype, thus may be associated with plaque vulnerability that will promote ACS.

Expression of developing neural transcription factors in lung carcinoid tumors.

In lung tumors, the association between carcinoids and high-grade neuroendocrine tumors (HGNETs) is controversial. To understand the phenotypic similarities/differences between lung carcinoids and HGNETs, we comparatively investigated the expression of three kinds of developing neural transcription factors (DNTFs: BRN2, TTF1 and ASCL1) and multiple endocrine neoplasia type 1 (MEN1) as well as RB1 and P53 using 18 carcinoids and 16 HGNETs. The DNTFs were expressed in 10 of the 18 carcinoids and in all the HGNETs, while normal neuroendocrine cells, which are considered the major cell origin of lung carcinoids and small cell carcinomas, did not express DNTFs. Both the DNTF(-) and DNTF(+) carcinoids contained typical and atypical carcinoids. All the DNTF(-) carcinoids examined were formed in the bronchial wall. All the MEN1(-) carcinoids examined were classified into the DNTF(-) carcinoids, while all the HGNETs expressed MEN1. This finding suggests that DNTF(-) MEN1(-) carcinoids are unlikely to be precursors of HGNETs. Although the status of RB1 and P53 between carcinoids and HGNETs were apparently different, the DNTF(+) carcinoids of two male patients and one female patient revealed morphologies resembling HGNET cells and relatively high Ki67 indices. Further investigation of DNTF expression in carcinoids might provide important clues to understand the association between carcinoids and HGNETs.

Calcium oxalate crystal deposition in a patient with Aspergilloma due to Aspergillus niger.

Discrimination between aspergilloma and chronic necrotizing pulmonary aspergillosis (CNPA) based on radiological findings can difficult. We describe a patient with aspergilloma and organizing pneumonia that was possibly caused by Aspergillus niger infection and radiologically mimicked CNPA. A postmortem histological analysis showed diffuse alveolar damage that had originated in peri-cavitary lung parenchyma. Calcium oxalate or Aspergillus niger was located inside, but not outside the cavity in the right upper lobe. Calcium oxalate or other unknown hyphal bioactive components might provoke severe lung inflammation not only adjacent to the cavity, but also on the contralateral side.

Nonfunctioning juxtaglomerular cell tumor.

The juxtaglomerular cell tumor (JGCT) is a rare renal tumor characterized by excessive renin secretion causing intractable hypertension and hypokalemia. However, asymptomatic nonfunctioning JGCT is extremely rare. Here, we report a case of nonfunctioning JGCT in a 31-year-old woman. The patient presented with a left renal tumor without hypertension or hypokalemia. Under a clinical diagnosis of renal cell carcinoma, radical nephrectomy was performed. The tumor was located in the middle portion adjacent to the renal pelvis, measuring 2 cm in size. Pathologically, the tumor was composed of cuboidal cells forming a solid arrangement, immunohistochemically positive for renin. Based on these findings, the tumor was diagnosed as JGCT. In cases with hyperreninism, preoperative diagnosis of JGCT is straightforward but difficult in nonfunctioning case. Generally, JGCT presents a benign biological behavior. Therefore, we should take nonfunctioning JGCT into the differential diagnoses for renal tumors, especially in younger patients to avoid excessive surgery.

POU domain transcription factor BRN2 is crucial for expression of ASCL1, ND1 and neuroendocrine marker molecules and cell growth in small cell lung cancer.

BRN2 is a developmental neural cell-specific POU domain transcription factor and is crucial for cell lineage determination. We investigated the importance of BRN2 in the expression of the lineage-specific transcription factors (achaete-scute homolog-like 1 (ASCL1) and NeuroD1 (ND1)) and neural/neuroendocrine marker molecules (neural cell adhesion molecule 1 (NCAM1), synaptophysin (SYP) and chromogranin A (CHGA)) in small cell lung cancer (SCLC) using cultured lung cancer cells. All examined SCLC cell lines expressed BRN2, as well as ASCL1, ND1, NCAM1, SYP and CHGA. The expression levels of ASCL1, ND1, NCAM1, SYP and CHGA considerably decreased when BRN2 was knocked down in SCLC cells, and the addition of a BRN2 transgene into non-SCLC (NSCLC) cells induced the expression of ASCL1, ND1, NCAM1, SYP and CHGA. However, the BRN2 gene was not activated by the forced expression of ASCL1 or ND1 in NSCLC cells. The knockdown of BRN2 caused significant growth retardation with decrease of S to G2 phase population and mitotic cell rates and unaltered Ki-67-labeled or apoptotic cell rates in SCLC cells, indicating increase of G1 phase population. These findings suggest that BRN2 is a higher level regulator than ASCL1 and ND1 and BRN2 might be involved in aggressiveness of SCLC.