Background: Postzygotic de novo mutations lead to the phenomenon of gene mosaicism. The 3 main types are called somatic, gonadal, and gonosomal mosaicism, which differ in terms of the body distribution of postzygotic mutations. Mosaicism has been reported occasionally in patients with primary immunodeficiency diseases (PIDs) since the early 1990s, but its real involvement has not been systematically addressed. Objective: We sought to investigate the incidence of gene mosaicism in patients with PIDs. Methods: The amplicon-based deep sequencing method was used in the 3 parts of the study that establish (1) the allele frequency of germline variants (n 5 100), (2) the incidence of parental gonosomal mosaicism in families with PIDs with de novo mutations (n 5 92), and (3) the incidence of mosaicism in families with PIDs with moderate-to-high suspicion of gene mosaicism (n 5 36). Additional investigations evaluated body distribution of postzygotic mutations, their stability over time, and their characteristics. Results: The range of allele frequency (44.1% to 55.6%) was established for germline variants. Those with minor allele frequencies of less than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%) of 128 families with PIDs, with a variable minor allele frequency (0.8% to 40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63.9%) was detected among families with moderateto-high suspicion of gene mosaicism. In most analyzed cases mosaicism was found to be both uniformly distributed and stable over time. Conclusion: This study represents the largest performed to date to investigate mosaicism in patients with PIDs, revealing that it affects approximately 25% of enrolled families. Our results might have serious consequences regarding treatment and genetic counseling and reinforce the use of next-generation sequencing-based methods in the routine analyses of PIDs.

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A case of photosensitivity induced by itraconazole is reported. A 70-year-old woman had erythema, oedema and vesicles on sun-exposed areas after 5 days of itraconazole treatment for oral candidiasis. Oral photochallenge using itraconazole and sun irradiation was positive, but photopatch test was negative. Photosensitivity from azoles is an uncommon adverse effect. Only three other cases have been described, two induced by ketoconazole and one by itraconazole.

Extraskeletal osteosarcoma is an uncommon neoplasm that usually arises in the deep soft tissues, especially in the lower extremities, with rare cases involving the subcutis or dermis. We report a 60-year-old man with an enlarging cutaneous mass in the right lower thigh. An incisional skin biopsy showed a well-defined, but non-encapsulated neoplasm, characterized by extensive cartilage with marked cellularity, atypia and high mitotic activity, involving the dermis and subcutis. Although osteoid or bone was not observed, a diagnosis of cutaneous chondroblastic osteosarcoma was suggested after excluding an origin in bone or other primary tumor sites by imaging techniques. Histopathologic features of the surgical specimen were characteristic, with a predominant high-grade chondroid component together with focal fibrosarcomatous zones, areas of multinucleated giant cells and foci of bone and osteoid formation. The patient underwent postoperative chemotherapy and is currently alive with pulmonary metastases 15 months after surgery. In summary, we report a unique case of cutaneous osteosarcoma of the chondroblastic subtype, diagnosed on incisional skin biopsy despite the absence of osteoid or bone during tumor sampling. As a rule, when an obviously malignant 'chondrosarcoma' is identified, one should always consider this entity.

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