Primary distal renal tubular acidosis: novel findings in patients studied by next-generation sequencing.

BACKGROUND: Primary distal renal tubular acidosis (DRTA) is a rare disease caused by loss-of-function mutations in at least three genes (ATP6V0A4, ATP6V1B1, and SLC4A1) involved in urinary distal acidification. The next-generation sequencing (NGS) technique facilitates the search for mutations in DRTA patients and helps to characterize the genetic and clinical spectrum of the disease. METHODS: Ten DRTA patients were studied. They had normal serum anion gap (AG), metabolic acidosis with simultaneous positive urinary AG, and inability to maximally acidify the urine. The exons of the three genes were sequenced in two pools by ultrasequencing. Putative mutations were confirmed by corresponding Sanger sequencing of each exon. RESULTS: We found 13 mutations in nine patients. ATP6V0A4: Intron16+2insA; p.R807Q; p.Q276fs; p.P395fs; Intron7-2T>C. ATP6V1B1: p.I386fs; p.R394Q. SLC4A1: p.V245M; p.R589C; p.R589H; p.G609A. One case was a compound heterozygous with a known mutation in ATP6V1B1 (p.G609R) and a pathogenic variation at SLC4A1 (p.E508K). One patient was negative for mutations. CONCLUSION: This study evidences that NGS is labor and cost effective for the analysis of DRTA genes. Our results show for the first time SLC4A1 gene mutations in Spanish patients and disclose that compound heterozygosity at two different genes can be responsible for DRTA.

Classification of cutaneous intravascular breast cancer metastases based on immunolabeling for blood and lymph vessels.

BACKGROUND: Intravascular breast cancer metastases to the skin can have several clinically distinct manifestations. Carcinoma telangiectoides, which presents as an erythematous patch with prominent telangiectasias or lymphangioma circumscriptum-like lesions, is a rare manifestation of cutaneous metastatic breast cancer and has been proposed to spread via dermal blood vessels. Carcinoma erysipelatoides, which presents as an erysipelas-like patch or plaque, has been proposed to spread via lymphatics. Clinical variants with nodular lesions that show tumor cells within vessels and in the extravascular space are seen more commonly. It has not been demonstrated conclusively whether dermal blood vessels or whether dermal lymph vessels are principally involved in these clinically distinct forms of cutaneous breast cancer metastases. OBJECTIVES: We sought to determine if carcinoma telangiectoides affects predominantly dermal blood vessels and if carcinoma erysipelatoides affects predominantly dermal lymph vessels. METHODS: Serial sections of biopsy specimens from patients with a characteristic clinical presentation of carcinoma telangiectoides and carcinoma erysipelatoides were labeled for cytokeratin to identify malignant cells. Subsequently, these sections were labeled for CD31 (a marker for blood and lymph vessels) and podoplanin (a marker for lymph vessels, but not for blood vessels), to differentiate blood vessels from lymph vessels in these sections. RESULTS: Sections from carcinoma telangiectoides showed malignant tumor cells strictly within dermal blood vessels, but not in lymph vessels. In contrast, sections from carcinoma erysipelatoides showed malignant tumor cells strictly in dermal lymphatics. LIMITATIONS: We used typical clinical cases to demonstrate the distinct involvement of blood and lymph vessels in these variants of cutaneous metastatic breast cancer. A larger case series is needed to confirm these findings. CONCLUSIONS: Immunolabeling for CD31 and podoplanin of cutaneous lesions of metastatic breast cancer confirms the spread of tumor cells predominantly via lymphatics in carcinoma erysipelatoides and predominantly via blood vessels in carcinoma telangiectoides.

Peripheral T-cell lymphoma with erysipelaslike spread.

An 88-year-old man from the Dominican Republic with a history of gastric adenocarcinoma was admitted with one month of fatigue, anorexia, weight loss, and abdominal pain. The dermatology department was consulted to evaluate an asymptomatic, shiny, firm, red nodule on the lower left chest, with an expanding rim of erythema. Skin biopsies were performed from the nodule and surrounding rim of erythema, which were both diagnostic of peripheral T-cell lymphoma (PTCL). This case is a unique example of PTCL with erysipelaslike spread.

Trachyonychia: case report and review of the literature.

Trachyonychia is the term used to describe nail plate roughness, pitting, and ridging that may affect 1 to 20 nails. Alopecia areata, psoriasis, lichen planus, atopic dermatitis, ichthyosis vulgaris, as well as other skin conditions have been associated with trachyonychia, but the causal relationship is often challenging to demonstrate histologically. Clinical evidence of these cutaneous disorders in conjunction with a nail matrix biopsy may help elucidate an etiology of trachyonychia, but many cases often remain idiopathic. Nail biopsy findings may match skin histology, but more commonly show spongiotic or nonspecific changes. We present an interesting case of a female with progressive development of trachyonychia in all 20 nails coinciding with a new diagnosis of sarcoidosis.