Pyoderma gangrenosum (PG) is a very rare, non-infectious, progressive inflammatory condition falling under the umbrella of neutrophilic dermatoses. It is an ulcerative condition with a wide variety of cutaneous manifestations and multiple clinical variants (classic ulcerative, pustular, bullous, and superficial granulomatous). Additionally, owing to similar patterns of mucocutaneous ulceration, it has certain overlaps with other neutrophilic diseases frequently observed in clinical practice. Pyoderma gangrenosum may occur in association with systemic conditions such as inflammatory bowel disease, hematological malignancies, or as a part of an inherited inflammatory syndrome. However, in rare cases, it may have an idiopathic origin as well. With no specific standardized diagnostic and treatment protocols in place, the management of pyoderma gangrenosum is primarily guided by pre-existing literature or is tailored according to the individual’s disease pattern, type, and associations. Currently, the pathophysiology of pyoderma gangrenosum remains elusive at best. All the aforementioned reasons contribute significantly to PG being labeled as a "diagnostic dilemma" or more commonly as a "diagnosis of exclusion" with frequent incidences of delayed diagnosis or misdiagnosis resulting in catastrophic delays in management. A 35-year-old Asian male presented with bilateral painful, violaceous ulcers with undermined edges involving the shins for the past three months. Routine investigations carried out were indicative of an underlying infection owing to a raised leucocyte count. Discharge from the lesion, however, showed no evidence of microbial growth. The ulcer progressively increased in size, despite optimal wound care and empirical treatment. Skin biopsy demonstrated central necrosis and ulceration of the epidermis and dermis with neutrophilic infiltrates. Phenomenon of pathergy was demonstrated following the formation of a new ulcer at the site of intravenous cannulation during hospital admission. Additionally, aggravation of pre-existing ulcers following their debridement was also indicative of a positive pathergy test. Ultimately, the diagnosis of pyoderma gangrenosum was made upon the successful exclusion of all the other differential diagnoses. Presence of an associated systemic disease could not be appreciated, leading to it being labeled as a case of idiopathic pyoderma gangrenosum. Supportive treatment with non-adhesive, moist dressings was initiated along with topical tacrolimus (0.1%) application. Treatment modalities utilized were steroids and azathioprine in divided doses owing to contraindications to the traditional option of cyclosporine. The patient showed a rapid response to steroids and azathioprine. The ulcers healed with characteristic cribriform scarring within three months of initiation of treatment.
Positron-emission tomography-magnetic resonance imaging (PET-MRI) is an emerging hybrid imaging modality that utilizes the superior soft tissue resolution of MR with the metabolic data from PET. In this study, we sought to assess the clinical value of fluorodeoxyglucose (FDG) PET-MRI with dedicated pelvic PET-MR in the initial staging of cervical cancer. In this institutional-approved study, we identified 23 adult females who underwent FDG PET-MRI on hybrid camera for staging of primary uterine cervical cancer that included a dedicated PET-MR of the pelvis. A nuclear medicine physician and a radiologist reviewed the PET, MRI, and fusion-body and pelvis images alone and then with consensus read characterizing PET and MR abnormal findings. There were 23 patients who underwent FDG PET-MRI for initial staging of cervical cancer with an average age of 52.2 ± 14.0 years. A total of 23 suspected lymph nodes in eight different patients were detected within the pelvis with increased metabolic activity on PET. Both the dedicated pelvis and whole-body PET imaging detected the same corresponding pelvic lymph nodes, although the pelvic PET imaging had better lymph node uptake delineation due to longer acquisition time. Using a 10-mm short-axis criterion, MRI identified only 43.5% of the FDG avid lymph nodes. The average SUVmax on the pelvis PET sequences was higher with SUV 8.9 ± 5.2 compared to the whole-body PET with SUV 7.8 ± 5.4 but was not statistically significant ( P > 0.05). Primary cervical cancer was identified in 18 patients on both PET imaging and MRI with dedicated MR pelvis providing better characterization. Based on our results of the patients with cervical cancer evaluated for initial staging, combining dedicated pelvic PET-MRI with whole-body PET/MR provides the most complete status of malignant disease in reference to delineation of primary tumor, involvement of surrounding tissues, and regional lymph nodes.
Ninety percent of female smokers begin smoking during adolescence, the developmental period for maximal mammary tissue differentiation. We and others have demonstrated in vitro that nicotine – a primary component of tobacco and electronic cigarettes ‐ evokes premalignant and malignant changes in mammary epithelial cells via activation of intrinsic nicotinic receptors. Accordingly, the risk of developing breast cancer increases with initial age of regular smoking activity, an average of 8 years earlier in our clinical study of breast cancer patients who started smoking as adolescents. However, the effects of nicotine alone (absent smoke components) on breast tumor induction remains to be determined. Likewise, the effect of nicotine exposure during adolescence have yet to be evaluated for mammary tissue.The objective of this study was to determine whether nicotine enhances mammary tumorigenesis in female rats and whether these effects are more pronounced in adolescent relative to adult animals.Nicotine (2 mg/kg) or saline was delivered via osmotic minipumps to female adolescent (P22) and adult (P55) rats (n=6–8 per treatment group). Following administration of 1‐methyl‐nitrosourea (MNU, for induction of mammary tumors) or vehicle, tumor development was monitored for 16 weeks. Number, size, time of appearance and stage of tumors were evaluated.Tumors arose in both MNU‐induced and nicotine only treatment groups. Twenty‐two tumors arose in nicotine‐treated rats (n=45) that included both MNU‐, and notably, nicotine‐only treated adolescents (2 tumors). No tumors arose in animals treated exclusively with saline. Adolescent animals developed tumors 4–6 weeks earlier than their adult counterparts: in adolescents, tumors first appeared following 8 weeks of nicotine exposure, while the mean time for appearance in adults was after 14 weeks of nicotine treatment. Tumor volumes were 5 times larger in nicotine‐treated adolescent rats, while tumors of nicotine‐treated adults were ~2 times greater than their saline counterparts. Extensive vascularization characterized tumors from both nicotine‐treated adolescents and adults. Tumors exhibited primarily cribriform and papillary lesions, indicating that the lesional cells showed proliferative activities and the ability to form mass lesions, thereby mimicking human tumors. However, the potential of these tumor cells to develop into invasive carcinomas and to metastasize needs to be further elucidated.Our study demonstrates that nicotine can induce and enhance mammary tumorigenesis in vivo. This is the first report of nicotine alone inducing mammary tumors. Nicotine exposure resulted in earlier tumor onset and increased tumor volume in both saline and MNU‐induction models. Notably, these effects were more pronounced in adolescent than adult female rats. Therefore, the implications of this study are that nicotine exposure acquired during teenage smoking of tobacco or e‐cigarettes may exert pronounced, adverse influences on subsequent development of breast cancer in women.Support or Funding InformationSupport was provided by Department of Pediatrics Intramural Grant Program, Stony Brook Children's Hospital and Stony Brook University School of Medicine
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