Toll-like receptors (TLRs) have first been characterized for their capacity to detect conserved microbial components like lipopolysaccharide (LPS) and double-stranded RNA, resulting in the elicitation of potent (innate) immune responses against invading pathogens. More recently, TLRs have also been shown to promote the activation of the cognate immune system against cancer cells. Today, only three TLR agonists are approved by FDA for use in humans: the bacillus Calmette-Guerin (BCG), monophosphoryl lipid A (MPL) and imiquimod. BCG (an attenuated strain of Mycobacterium bovis) is mainly used as a vaccine against tuberculosis, but also for the immunotherapy of in situ bladder carcinoma. MPL (derived from the LPS of Salmonella minnesota) is included in the formulation of Cervarix®, a vaccine against human papillomavirus-16 and -18. Imiquimod (a synthetic imidazoquinoline) is routinely employed for actinic keratosis, superficial basal cell carcinoma, and external genital warts (condylomata acuminata). In this Trial Watch, we will summarize the results of recently completed clinical trials and discuss the progress of ongoing studies that have evaluated/are evaluating FDA-approved TLR agonists as off-label medications for cancer therapy.

https://www.tandfonline.com/doi/pdf/10.4161/onci.20931

Trial watch: FDA-approved Toll-like receptor agonists for cancer therapy.

Introduction:Pilomatrixoma, also known as calcifying epithelioma of Malherbe, is a superficial benign skin tumor that arises from hair follicle matrix cells. Although pilomatrixomas are well-recognized lesions, clinically they are frequently misdiagnosed as other skin conditions. By reviewing all th

Pilomatrixoma: A Comprehensive Review of the Literature.

Background Pilomatrix carcinoma is a rare cutaneous tumor derived from follicular matrix cells with few cases documented in the literature. Objective We sought to better characterize this tumor by analyzing its epidemiologic, clinical, and histopathologic features in 13 new cases and by reviewing the literature. Methods All cases of pilomatrix carcinoma from a large regional dermatopathology practice were identified and analyzed by chart review for clinical and histopathologic characteristics. Similar characteristics were compiled from an additional 123 cases in the English-language literature. Cox proportional hazards regression models were used to determine risk factors associated with the development of metastasis for all identified metastatic tumors. Results Our 13 tumors were most common in middle-aged to older white men and presented mostly on the head/neck. Histopathologically, tumors were asymmetric, were poorly circumscribed, were composed of basaloid and "ghost" cells, had frequent atypical mitoses, and had infrequent lymphovascular invasion. Wide excision was considered the most definitive treatment modality, but local recurrence was common. When analyzing all reported cases of metastasis using statistics, metastasis was significantly associated (hazard ratio 3.45, P Limitations The retrospective, single-center design and the reliance on electronic medical records are limitations. Conclusions This study helps better characterize pilomatrix carcinoma and identifies potential predictors of metastasis.

https://www.jaad.org/article/S0190-9622(14)01160-8/pdf

Pilomatrix carcinoma: 13 new cases and review of the literature with emphasis on predictors of metastasis.

Pilomatrix carcinoma is a rare, locally aggressive tumor with a tendency to recur. Distant metastases have been reported, with pulmonary lesions being the most frequent manifestation. Similar to pilomatrixoma, pilomatrix carcinoma typically presents as a nontender, firm dermal swelling and is found most commonly in the head and neck region. Although pilomatrixomas and pilomatrix carcinoma are well-recognized lesions, clinically they are frequently misdiagnosed as other skin conditions. By reviewing the literature over the past 10 years, the aims of this review are to analyze the cause, clinical presentation, histopathologic features, management and outcomes of pilomatrix carcinoma amongst children and adults.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/cup.13046

Pilomatrix carcinoma: 12‐year experience and review of the literature

Pilomatrixoma is a common benign neoplasm of children and young adults with a female predilection. In contrast, its malignant counterpart, pilomatrix carcinoma is a rare neoplasm of older adults with a male preponderance. Pilomatrix carcinomas are locally aggressive with a tendency to recur. We report a case of a 44-year-old male who presented with an enlarging soft tissue tumor on the right upper back. Histology revealed an asymmetric, poorly circumscribed, lobulated neoplasm located deeply in the dermis with infiltration into the underlying subcutaneous tissue. The tumor was comprised of basaloid cells containing vesicular nuclei, prominent nucleoli, scant cytoplasm, and brisk mitotic activity. A focus of basaloid cells transitioning to shadow cells with central keratinized material and tumor necrosis was also present. The diagnosis of a pilomatrix carcinoma was rendered. Considering the infiltrative nature of this neoplasm with perineural and intramuscular invasion, the patient underwent 3 surgical excisions before it was completely removed.

Pilomatrix carcinoma: a case report and review of the literature.

Pilomatrix carcinoma is a rare malignant counterpart of pilomatricoma. To our knowledge, only approximately 90 cases have been published in English literature. Pilomatrix carcinoma is locally aggressive and occasionally shows rapid progression infiltrating to the muscle, bone and vessels. We report a case of pilomatrix carcinoma that developed in a 38-year-old man and started to grow after a long stable period, relapsed for a short time and infiltrated into the muscle underneath. While the initial skin biopsy showed histopathological findings consistent with pilomatricoma, the recurrent tumor contained marked cellular atypia and an aggressive growth pattern. Although it is still controversial whether pilomatrix carcinoma arises de novo or through malignant transformation of a pilomatricoma, the present case might be caused by the latter process considering the patient's clinical course. beta-catenin is a downstream effecter in the canonical pathway of Wnt, acting as a signal for cell differentiation and proliferation. The characteristic nuclear staining pattern of beta-catenin in the basaloid tumor cells, which is usually observed in pilomatrix carcinoma, supported the diagnosis of pilomatrix carcinoma in the present case.

Pilomatrix carcinoma arising from pilomatricoma after 10‐year senescent period: Immunohistochemical analysis

Many reports have shown the efficacy of topical imiquimod in patients with skin carcinoma. This effect is based on the activity of imiquimod as an immune-response modifier. The present authors hypothesized that this agent could also be used to treat skin metastatic lesion from renal cell carcinoma. The present authors report the case of a 54-year-old man who presented with a metastasis renal cell carcinoma lesion on his nose. He had a history of right nephrectomy performed 4 years previously. The present authors started him on topical treatment with imiquimod 5% cream three times a week for his nose lesion. A reduction of the lesion was observed after 2 months, and during the following 12 months no sign of recurrence was observed.

Imiquimod 5% cream for the treatment of nasal lesion of metastatic renal cell carcinoma

Anogenital granulomatosis (AGG) is a rare chronic idiopathic disorder presenting as a painless swelling of the vulva, labia, penis, and/or anogenital area. Some AGG cases have been diagnosed along with Crohn’s disease (CD). We report a case of AGG that led to diagnosis of underlying CD, namely Cutaneous Crohn’s disease (CCD). We guess that CCD appeared in the anogenital region is equal to AGG with CD.

/pdf/cutaneous-crohn-s-disease-and-anogenital-granulomatosis-with-4btoqwdhiy.pdf

Cutaneous Crohn's Disease and Anogenital Granulomatosis with Crohn's Disease: Many Names for the Same Clinical Entity

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Pilomatrix carcinoma arising from pilomatricoma after 10‐year senescent period: Immunohistochemical analysis

Imiquimod 5% cream for the treatment of nasal lesion of metastatic renal cell carcinoma

Cutaneous Crohn's Disease and Anogenital Granulomatosis with Crohn's Disease: Many Names for the Same Clinical Entity