Clinicopathologic Features and Prognostic Significance of Immunohistochemistry and In Situ Hybridization Based Molecular Classification in Gastric Carcinoma.

BACKGROUND/AIM: Gastric carcinoma (GC) is a highly heterogeneous disease with many subtypes that have different morphologic and molecular characteristics. In the current study, we analyzed immunohistochemical (IHC) and in situ hybridization (ISH) features of GCs and evaluated their association with prognosis and clinicopathological features. MATERIALS AND METHODS: Three hundred cases analyzed by IHC and ISH for microsatellite stability, p53, e-cadherin, HER2, PD-L1 expression, and Epstein-Barr virus (EBV) status. Cases were classified into five subgroups based on expression profile. The relationships between subgroups, clinicopathological features, and survival were determined. RESULTS: Ten (3.3%) cases were classified as EBV-associated, 45 (15%) as microsatellite instable (MSI), 73 (24.3%) as EBV-/microsatellite-stable (MSS)/epithelial-mesenchymal-transformation (EMT)-like, 75 (25%) as EBV-/MSS/ non-EMT-like/p53+, and 97 (32.3%) as EBV-/MSS/non-EMT-like/p53-. The MSI subtype had the best overall survival (OS). In contrast, the EBV-/MSS/EMT-like subtype had the poorest OS. The MSI subtype was also related with old age of the patient and antrum-corpus localized tumors, whereas the EBV-/MSS/EMT-like was associated with young age, larger tumor size, and advanced stage presentation. PD-L1 positivity is highly correlated with MSI and EBV-associated subtypes. CONCLUSION: Our data demonstrated a link between IHC/ISH characteristics of GC and clinical outcomes. IHC/ISH based molecular classification may be helpful in predicting the survival.

Giant Mongolian macules with bilateral ocular involvement: case report and review.

Dermal melanocytosis is characterized by the presence of spindle-shaped melanocytes in the dermis. The most common form is Mongolian spots. A 15-month-old girl from Azerbaijan had a systematized dark blue-gray hyperpigmentation on her shoulder, back and extremities. The hyperpigmentation was also found on both sclera and choroidal areas, without any other facial involvement. On histopathological examination, dense melanocytes were found on the intermediate and deep dermis. Her physical and mental development was normal. This association of blue macules and involvement of both sclerae does not represent a distinct entity and cannot be categorized as an example of nevus of Ota.

Anti-TNF agent etanercept augments UV-induced skin cancer development in SKH-1 mice.

BACKGROUND: Despite being employed in the treatment of inflammatory disorders for more than 20 years all over the world, data regarding photocarcinogenic risks of anti-TNF agents is scarce. OBJECTIVE: To assess photocarcinogenic potential of anti-TNF agents. METHODS: This was a placebo controlled, split-body (UVB-treated versus -untreated) study on mice. Treatment groups were infliximab (n = 11), etanercept (n = 11), cyclosporine (n = 11) and vehicle control (n = 11). Agents were introduced on the 10th week of phototherapy and continued through 24th week. The macroscopic, histological and immunohistochemical analysis of test sites were carried out. RESULTS: Overall 132 tumors were detected on test sites. All of these tumors developed on UV-exposed sides. Histologic examination of these tumors was compatible with keratinocytic neoplasia in 128, mastocytosis in 3, epidermal cyst in 1. Median tumor burden in the UVB exposed areas for ETN, IFX, CYC, and control groups were 14.91, 10.20, 6.28, and 3.14 cm2, respectively. ETN group demonstrated both higher tumor burden and keratinocytic neoplasia numbers than controls (p = .03, p = .025). Although there were 1.8 and 1.7 times more keratinocytic neoplasms in IFX and CYC groups compared to controls, these differences didn't reach statistically significant levels (p = .14; p = .19). CONCLUSION: This study points out to a significant photocarcinogenic potential of anti-TNF agent etanercept.

An uncommon presentation of the co-existence of morphea and vitiligo in a patient with chronic hepatitis B virus infection: is there a possible association with autoimmunity?

A 30-year-old man presented with indurated violaceous plaques all over his body that had been present for 7 months. The patient had also had vitiligo for 3.5 years, and hepatitis B virus (HBV) infection and cirrhosis for a 2-year period. Histopathologic examination of the indurated plaques confirmed the diagnosis of morphea. Localized scleroderma and vitiligo have only rarely been reported to occur simultaneously. Although the etiologies of vitiligo and morphea are both uncertain, their association with autoimmune diseases favors an autoimmune hypothesis. Both vitiligo and morphea might have appeared coincidentally. However, this association could be significant because it may be related to the presence of HBV and alterations in the immune system that are caused by this virus. Therefore, this rare combination of vitiligo and morphea in a patient with chronic HBV infection warrants attention because it suggests a possible immunologic association, which may merit future study.

Transient efficacy of double high-dose chemotherapy and autologous peripheral stem cell transplantation, immunoglobulin, thalidomide, and bortezomib in the treatment of scleromyxedema.

Scleromyxedema is a rare disorder characterized by mucin deposits in the dermis and monoclonal gammopathy. No definitive treatment of this condition has been described to date. We present the case of a 38-year-old male patient with scleromyxedema who underwent double consecutive autologous peripheral stem cell transplantations and received immunoglobulin, thalidomide, and bortezomib. This resulted in considerable clinical and pathologic amelioration of the patient's condition. However, 3 years after the second transplant, the patient relapsed and manifested the same skin lesions evident at his initial presentation.

Uncommon presentation of mycosis fungoides: eyelid margin involvement.

Mycosis fungoides is a cutaneous T-cell lymphoma that has been rarely reported to involve ocular structures. A 33-year-old woman who had received therapy for mycosis fungoides on the trunk for 11 years, presented to our clinic with new plaques and tumors on her eyebrows and eyelid margin, and alopecia of her eyelashes and eyebrow. The histopathological examinations supported the diagnosis of mycosis fungoides. There was no intraocular involvement with tumor. The mycosis fungoides was of stage II B, and the patient was referred to medical oncology and radiation oncology clinics for treatment. She was placed on a radiotherapy schedule. The involvement of mycosis fungoides in the ocular area is rare in the published work. The importance of eye involvement is being seen in advanced cases, and there is a possible association between mycosis fungoides and poor prognosis by being an indicator of systemic involvement.

Annular lupus vulgaris: an unusual case undiagnosed for five years.

Tuberculosis is still a serious problem in both developing and developed countries. It is often confused with various cutaneous disorders both clinically and histopathologically.A 46-year-old woman attended our clinic with progressive, asymptomatic, annular skin lesions on her right upper extremity for 5 years. She had received many different therapies for these lesions at other institutions previously but these medications were not effective and the lesions deteriorated. On dermatological examination, well-demarcated, irregular bordered, violaceous colored, elevated and crusted annular lesions on her right hand dorsum and forearm were observed. She was diagnosed as having lupus vulgaris clinically and histopathologically. Antituberculosis therapy was administered and regression of the lesions started in the second week of medication.We report a case of long-standing, undiagnosed and uncommon, annular form of lupus vulgaris. We want to stress that clinical and histopathological findings are still important for the diagnosis of cutaneous tuberculosis.

Eosinophilic pustular folliculitis: the first case associated with hepatitis C virus.

Eosinophilic pustular folliculitis is a rare disorder that is characterized by recurrent crops of papules and pustules localized on seborrheic areas of the body. The etiopathogenesis of the disease is still unknown, but it has been related to infections and immunosuppressive states. This report is the first case to be found to be related to hepatitis C virus infection.

Bullous eosinophilic cellulitis succession with eosinophilic pustular folliculitis without eosinophilia.

Eosinophilic cellulitis is characterized clinically by an acute dermatitis resembling cellulitis with unknown etiology. Eosinophilic pustular folliculitis is also a rare inflammatory dermatosis characterized by recurrent crops of erythematous follicular papulopustules that coalesce to form annular plaques with unclear etiopathogenesis. We describe a 20-year-old white male who had vesiculobullous and plaque-like lesions on the hands and feet and was diagnosed with bullous eosinophilic cellulitis clinically and histologically without any etiological agents. Following therapy with oral corticosteroid and oral tetracycline capsules, the lesions disappeared. After a 2-month asymptomatic period, the patient developed pruritic follicular papules and pustules on the lower and upper extremities and upper back. Stool examination revealed Gierdia intestinalis eggs. The patient had complete clearance with treatment of ornidazol for 2 weeks and indomethacin for 2 months. This is the first report of bullous eosinophilic cellulitis coexisting with eosinophilic pustular folliculitis without eosinophilia in the English published work.

Colocalization of lichen planus and vitiligo associated with selective IgA deficiency.

A 28-year-old man with a diagnosis of vitiligo universalis for 6 years presented with reddish polygonal papules that had developed on his left hand first and then on his right hand. On dermatologic examination, porcelain-white hypopigmented appearance was observed all over his body, and there were violaceous, flat-topped papules changing from 2 to 5 mm in diameter localized on the hypopigmented areas of the dorsum of both hands and flexor sites (Figure 1). The physical examination and laboratory investigations including hemogram, erythrocyte sedimentation rate, serum biochemistry, and urinanalysis were normal. Antibodies to thyroid tissue, hepatitis viruses, human immunodeficiency virus, nuclear, and streptolysine were negative. Repeated IgA levels in serum were found to be decreased; however, the other immunoglobulins (IgG, IgM) and C3, C4 and cryoglobulins were in normal ranges. Histopathologic examination of the polygonal papules revealed hyperkeratosis, focal thickening of the granular layer, and irregular acanthosis in triangular saw-tooth pattern. The basal layer was invaded by the lymphocytic inflammatory infiltrate and had numerous necrotic keratinocytes. The infiltrate in the upper dermis was band-like and sharply demarcated at its lower border. There were also a few melanophages in the upper dermis. Melanocytes were decreased in number, and in some areas they were absent at the basal layer of epidermis. Clinical and histopathologic diagnosis were consistent with lichen planus and vitiligo (Figure 2).

Linear and whorled nevoid hypermelanosis.

Linear and whorled nevoid hypermelanosis (LWNH) is a rare skin condition characterized by swirls and whorls of hyperpigmented macules in a reticulate pattern along Blaschko's lines; approximately 40 cases have been reported in the English language literature. We report a case of LWNH occurring in a 20-year-old man with widespread involvement over the trunk, face, upper limbs, and genitalia in association with scoliosis. A small hyperpigmented area on the abdomen was treated with a medium-depth chemical peel regimen using 70 percent glycolic acid and 35 percent trichloroacetic acid with no benefit. This is the first report of LWNH treated with medium-depth chemical peel.

A case of generalized discoid lupus erythematosus: successful treatment with imiquimod cream 5%.

Discoid lupus erythematosus (DLE) is the most common form of chronic cutaneous lupus erythematosus. Classic DLE lesions begin as red-purple macules, papules, or small plaques and rapidly develop a hyperkeratotic surface. Most patients with untreated classic DLE lesions suffer indolent progression to large areas of cutaneous dystrophy and scarring alopecia that can be psychosocially devastating. A 44-year old male patient presented to the clinic with erythematous scaly patches that began on his nose 1 y before. His face was most affected, however, lesions were also noted on his scalp, ears, and limbs. Histopathologic examination verified a diagnosis of DLE. Laboratory examinations and consultations revealed no signs of systemic involvement. Imiquimod cream 5% was applied to the lesions once a day 3 times a week. After 20 applications, entire lesions regressed significantly. Imiquimod cream 5% may represent an alternative treatment method for patients with DLE.

Disseminated lobular capillary hemangioma: two case reports.

Lobular capillary hemangioma, also known as pyogenic granuloma, is a common, solitary, benign neoplasm of the skin and mucous membranes. The etiology of this lesion remains unknown. Lobular capillary hemangioma can present rarely in a disseminated form, usually associated with other disorders. Two patients, aged 17 and 33, were admitted to the dermatology clinic with disseminated lobular capillary hemangiomas which appeared suddenly. There was no history of trauma in either case. The histopathology of the lesions was consistent with lobular capillary hemangioma. No associated disorders were found in physical and laboratory examinations other than mental retardation in one patient and a small hemangioma in the liver in the other. We report two cases of disseminated lobular capillary hemangioma without an associated disorder.

Role of anorectal myectomy in the treatment of short segment Hirschsprung's disease in young adults.

Basic pathological disorder in Hirschsprung's disease (HD) comes into being by the abnormal innervations of the aganglionic distal intestine. The nonserious forms of this congenital disease may reach the young by proceeding with chronic, obstinate constipation that does not respond to diet. Myectomy of the short segment of aganglionic part may provide diagnostic and therapeutic value. Between 1993 and 2003, anorectal posterior myectomy was performed in 19 patients diagnosed with HD. The mean age of patients was 23 years. Previous or concomitant anterior resection was added to the procedure in seven cases due to dolicomegacolon. In addition to the deficiency of anorectal inhibitor reflex (ARIR) among all patients, the frequency of defecation was 12.5 days (range, 6-30 days) before operation. Anorectal length before widening was an average of 5.5 cm (range, 2-8 cm). All pathologic specimens were found to be aganglionic. Postoperatively, the mean of first regular defecation interval was 1.5 days (range, 1-3 days). Involution of rectum was evaluated with a rectal examination and barium enema X-rays during follow-up. ARIR of patients also returned to normal. In conclusion, anorectal posterior myectomy is an effective operation in diagnosis and treatment of short-segment HD. Furthermore, colon resection annexed to this operation, in the condition of dolicomegacolon, is also used to remove obstinate constipation.

Fulminant pseudomembranous colitis of the left colon successfully treated by surgical resection.

Pseudomembranous colitis is the classical and most dramatic manifestation of Clostridium difficile infection. Surgery is required for patients with perforation and for those who fail to respond to medical treatment. This is a report of a patient with severe pseudomembranous inflammation confined to the left colon, which was successfully treated by surgical resection.

A case of pachyonychia congenita with unusual manifestations: an unusual type or a new syndrome?

A 30-year-old man presented with lesions on his oral mucosa and soles. There were no similar complaints in his family members. The dermatological examination revealed follicular hyperkeratosis on his trunk and upper extremities and flesh-colored, firm cystic lesions on his axillae. He had focal, painful, hyperkeratotic areas sited particularly on both his soles and palms. In addition to these, leukokeratosis and ulcerative areas on buccal, labial mucosa, tongue, and at corners of the mouth, and complete loss of teeth was observed. The proximal layering was revealed on all of his nails. The laboratory investigations produced normal results except the deficiency of immunoglobulin A. The psychiatric examination revealed mild mental retardation. Keratin gene (KRT6a, KRT6b, KRT16, and KRT17) mutations for pachyonychia congenita were negative. He got removable dental prosthesis because of inadequate alimentation. Squamous cell cancer developed on lower lip mucosa during follow-up. We present an individual who had different nail dystrophy, epidermal cysts, mental retardation, blepharitis, complete loss of teeth, and negative keratin gene mutations for pachyonychia congenita and developed squamous cell cancer on the oral leukokeratosis lesions. We think that the present case may be an unusual new type of pachyonychia congenita.

Nevus sebaceus with basal cell carcinoma, poroma, and verruca vulgaris.

Nevus sebaceus (NS) is a congenital, benign, hamartomatous lesion and it is possible to see several benign or malignant tumors accompanying it. One of these is the poroma, which is very rare, and has only been reported twice before, in the English literature. In this paper, we presented two new cases of NS. One of them was a 40-year-old male who presented with a congenital skin lesion on his temporoparietal region. This lesion was composed of four different lesions, including NS, poroma, basal cell carcinoma (BCC), and verruca vulgaris. The second patient was a 41-year-old male presenting with a yellow-brown patch on the scalp. This lesion was comprised of NS and BCC. In addition to these presentations, we discussed the differential diagnosis between BCC and trichoblastoma, both of which are likely to be seen with NS. For this purpose, we recommended an immunohistological panel, which may be useful for differentiating these two morphologically similar lesions.

Molecular alterations in malignant blue nevi and related blue lesions.

Malignant blue nevi (MBN) are extremely rare dermal melanocytic tumors that arise in association with atypical cellular blue nevi (ACBN), cellular blue nevi (CBN), common blue nevi (BN), or de novo. The frequency of BRAF, NRAS, and KIT mutations in malignant melanoma varies according to histological subtype and localization. These mutations are rarely observed in blue nevi, which have recently been shown to carry activating mutations in GNAQ/GNA11 genes. Only few small molecular studies of MBN have been published. The aim of the present study was to analyze in MBN and related blue lesions such as ACBN, CBN, and BN the prevalence of BRAF, NRAS, KIT, GNAQ, and GNA11 gene mutations and their association with clinicopathological features. We included in our study 12 MBN, 6 ACBN, 29 CBN, and 35 common BN diagnosed between 1996 and 2014. Sanger sequencing method was used for mutation analysis. Overall, GNAQ exon 5 mutation was the most frequent alteration (46 %), in 2 of 12 (17 %) MBN, 1 of 6 (17 %) ACBN, 22 of 29 (76 %) CBN, and 13 of 35 (37 %) common BN. BRAF V600E and GNA11 exon 5 mutations were respectively detected in 3 of 12 (25 %) and in 2 of 12 (17 %) MBN while none in ACBN, CBN, and common BN. None of the cases harbored NRAS exon 2/3, KIT exon 9/11/13/17/18, or GNAQ/GNA11 exon 4 mutations. GNAQ gene exon 5 mutations are rare in MBN and ACBN but frequent in CBN and common BN. Remarkably, BRAF V600E and GNA11 exon 5 mutations were only detected in MBN, whereas none were found in ACBN, CBN, or common BN. Our data contribute new elements to the limited data on molecular alterations in MBN.