Angioleiomyoma is a benign smooth muscle tumor of the subcutis. The presence of mature adipocytes has been described in this tumor under the rubric of 'angiolipoleiomyoma' or, erroneously, 'angiomyolipoma' (these are not PEComas). Previous studies have found adipocytes in only 2-3% of angioleiomyoma. Anecdotally, the incidence appeared to be greater than this in our practice. Moreover, the presence of adipocytes has not been evaluated in pilar leiomyoma or cutaneous leiomyosarcoma. We searched the pathology archives from 2007 to 2014 for all cutaneous and subcutaneous leiomyoma and leiomyosarcoma; cases were reviewed to confirm the diagnosis and evaluate for mature adipocytes. Seven of 73 total cases (10%) contained mature adipocytes: 1 of 33 pilar leiomyoma (3%), 4 of 22 angioleiomyoma (18%) and 2 of 18 leiomyosarcoma (11%). In our series, the 18% incidence of 'angioleiomyoma with fat' (our preferred terminology) is higher than the previously reported incidence of 2-3%. We also report the rare presence of mature adipocytes within pilar leiomyoma and cutaneous leiomyosarcoma, a finding not previously reported to our knowledge. Mature adipocytes may be present within cutaneous and subcutaneous leiomyomas and leiomyosarcomas and should not detract from the diagnosis or lead to concern for an adipocytic neoplasm or PEComa.
A 20‐year‐old male presented with multiple subcutaneous nodules on the head, neck, chest and oral cavity. FNA and biopsy showed pigmented fungal hyphae diagnostic of multifocal phaeohyphomycosis, found to be Exophiala spinifera by molecular diagnostics. The presentation initially raised concern for disseminated disease and occult immunosuppression. However, the patient appeared to be immunocompetent and otherwise healthy. Upon further inquiry, the patient was in a motor vehicle accident 4 years before presentation; he was ejected into a vegetable field resulting in multiple open wounds. Multifocal phaeohyphomycosis usually indicates disseminated systemic disease from immunosuppression and carries a grave prognosis.
Abstract Pleomorphic fibromas are rare benign cutaneous neoplasms associated with deletion/loss of chromosomes 13q and 17p, where RB1 and TP53 are located, respectively. Herein, we report five cases of pleomorphic fibroma arising in patients with germline TP53 mutations, suggesting a potential link with Li‐Fraumeni syndrome. All three patients were female and young (mean age 27) with a strong personal and/or family oncologic history and confirmed pathogenic germline TP53 mutations. In two patients, multiple pleomorphic fibromas were diagnosed. Clinically, the lesions arose at various cutaneous sites and were small (≤2 cm) and raised (4/5). Histopathologically, the tumors were paucicellular, composed of atypical spindled to stellate cells with hyperchromatic and variably pleomorphic nuclei. Mitotic activity was exceedingly low, although rare atypical mitotic figures were seen in one case. Immunohistochemically, the tumor cells were diffusely positive for p16 (3/3) and showed loss of Rb expression (5/5). All cases showed aberrant p53 expression (overexpression in 4, complete loss in 1). The tumors have followed a benign clinical course with no evidence of progression or recurrence. In conclusion, the development of multiple pleomorphic fibromas in a young patient may be a clue to an underlying genetic cancer syndrome involving TP53 .
Abstract: Rhabdomyosarcoma (RMS) rarely arises as a primary skin tumor. It is also very rare in older adults, especially the alveolar type. We report an 80-year-old White woman who presented with a painful, erythematous, raised lesion (2 × 3.5 cm) above the left knee that was fixed within the skin, yet mobile about underlying soft tissue. A punch biopsy showed monotonous malignant round blue cells involving the dermis. Immunostains showed diffuse expression of CD56, focal chromogranin, focal dot-like pancytokeratin, CK7, and neurofilament, but negative for synaptophysin, CK20, SOX-10, MUM-1, CD43, TTF-1, and CD99. A CK20-negative variant of Merkel cell carcinoma was initially favored, but given the unusual immunophenotype and the presence of cellular dyscohesion, desmin and myogenin stains were performed, both of which were diffusely positive. Molecular testing revealed rearrangement of PAX3 and FOXO1 loci, confirming the diagnosis of alveolar RMS. PET/CT showed a probable 1.9-cm left inguinal lymph node metastasis; no internal or deep soft tissue primary tumor mass was identified, supporting a true primary cutaneous origin. Alveolar RMS may express keratins and neuroendocrine markers, making it easy to confuse with Merkel cell carcinoma on those exceptionally rare instances, when it arises in the skin of older adults.
Dermatologists often use skin biopsy to arrive at a diagnosis; interpretation of such biopsies requires an expert pathologist/dermatopathologist. In many medical colleges across India, skin pathology is a neglected specialty and is not adequately taught to trainees in pathology. India has very few expert pathologists to deal with skin pathology, and those experts that are available are usually in large metropolitan areas. Dermatologists practicing in small cities or rural areas often struggle to find a pathologist with dermatopathology expertise to opine on a difficult skin biopsy. A dermatologist in such a setting often must send the skin biopsy bottle through postal or courier service to an expert pathologist/dermatopathologist in a larger city who will process the tissue and send the diagnosis back to the dermatologist through email or courier service. This method often requires 15 days for a dermatologist to acquire the report, and this may lead to delay in initiation of appropriate treatment especially for serious or urgent diagnoses. Furthermore, as many remote areas lack adequate courier and transportation services, the problem is compounded, and the dermatology consultant is often forced to provide empirical treatment without histologic confirmation of the diagnosis. A great portion of the rural Indian population is therefore lacking access to advanced medical care for complex or serious cutaneous disease, which is a significant public health problem. Online social media and networking sites (Facebook, Twitter, and Whatsapp) may help circumvent this vexing problem. Dermatologists can locally process the skin biopsy with the help of a pathology laboratory, procure the slides, and obtain photomicrographs. If a mounted microscope camera is not available, smartphones may be used to capture the microscopic images, either through an adaptor1,2 or through a free-hand technique (see YouTube demonstration video by Dr. Annie Morrison: https://youtu.be/cfd9ViHBlR4).3,4 Photomicrographs along with clinical photographs and clinical history of the patient can then be shared with pathologists and dermatopathologists from around the world through Facebook discussion groups, Twitter, or other online forums (Figs. 1A–E).5 This allows numerous pathologists and dermatopathologists from around the world to view the case and to share their diagnostic ideas and opinions in real-time. Some cases receive multiple comments within only hours of posting to a Facebook group. Other users are able to ask the original posting dermatologists questions about the clinical scenario, as well as to help triage cases that may require more complex workup including immunohistochemical stains or molecular testing. Those latter ancillary tests may not be available locally, but this information may be useful in helping the local treating dermatologist to decide whether referral of the patient on to a larger medical center may be the best course of action. Thus, a variety of opinions can potentially be obtained very quickly from a plethora of pathologists/dermatopathologists. Online forums allow 2-way live interaction between dermatologists and pathologists, a valuable form of interaction that is usually lacking in most traditional medical practice settings in India and the United States. Such interactions are fruitful to both parties: they allow the dermatologist to learn about the finer nuances of skin pathology and likewise for the pathologist to learn more about the clinical aspects of dermatology. Pathologists may gain greater appreciation of the struggles faced by dermatologists and patients in developing areas of the world. There are also many differences in how to approach dermatopathology diagnosis when ancillary techniques are not available; these online interactions may help to enhance and further develop clinical thinking skills, diagnostic triage, and reliance on morphologic features in those pathologists and dermatopathologists participating in online discussions about these kinds of cases. These skill sets are crucial in all diagnostic practice settings, yet they may become atrophied when pathologists practice in a setting with an abundance of available ancillary tests. Therefore, it is not only the patients and dermatologists who benefit from these social media and online forum interactions but also the pathologists and dermatopathologists.FIGURE 1.: A–E, An example of sharing a difficult dermatology/dermatopathology case on a Facebook discussion group. The pathologist working with the local dermatologist posts clinical images and information (A) as well as histologic images from the biopsy (B and C). Members of the group discuss the differential diagnosis (D). The original pathologist who posted the case performed additional workup after discussion with the group and then arrived at a final diagnosis (E). As these screenshots show, the discussion is robust, educational, and beneficial to all parties involved. Case courtesy of Dr. Romualdo Correia Lins Filho (https://www.facebook.com/groups/dermatopathology/permalink/1616468891702653/).Despite the profound benefits of social media in obtaining diagnostic opinions on difficult cases, there are some limitations that should be discussed and considered. The first is patient privacy. In the United States, patient privacy is protected by law: the Health Insurance Portability and Accountability Act of 1996 (commonly referred to as HIPAA). Even more important than any law, privacy is an ethical principle and basic human right for all medical patients. Protecting patient privacy has been a deeply respected tradition among physicians for over 2000 years, being mentioned even in the original Hippocratic Oath.6 The most basic rule of respecting patient privacy online is the same as in our everyday practices: do not reveal any information that would allow the patient to be identified. In the United States, the HIPAA law defines 18 data points that are classified as "patient identifiers."7 These identifiers may not be publicly disclosed without explicit permission from the patient. Even in jurisdictions where HIPAA or a similar law does not apply, this list serves as a useful reminder of which details to avoid revealing online when sharing any case. Crane and Gardner have written in greater detail on the topic of patient privacy and online pathology image sharing, and they provide a variety of recommendations for ensuring that privacy is never compromised when sharing a case on social media. In their view, patient consent is not required for sharing de-identified images of a case on social media. In fact, they suggest that the ethical and HIPAA considerations for sharing de-identified pathology or dermatology images on social media is similar to those required for publishing images in the peer-reviewed medical literature.8 Another potential limitation of sharing pathology cases online is image quality. For pathologists and dermatopathologists, "H&E is king." Diagnosis always begins with a high-quality H&E (hematoxylin and eosin) section of the tissue for morphologic evaluation under the microscope. Obtaining high-quality H&E sections of skin biopsies requires proper fixation, tissue processing, paraffin embedding, sectioning by an experienced histotechnologist, and finally, application of H&E stain using a validated protocol and high-quality reagents. These steps are often taken for granted by pathologists and dermatopathologists practicing in large centers or advanced laboratories who are used to seeing pristine quality H&E sections daily. Yet, in laboratories in developing or low-resource geographic areas, one or more of these steps may be difficult to accomplish, leading to poor-quality H&E sections. Sharing images of poor-quality H&E sections (or low resolution photographs) greatly reduces the ability for other pathologists and dermatopathologists online to evaluate and comment on a case. Furthermore, in the experience of the authors, cases posted with only low-quality H&E images often receive few if any comments or opinions; this defeats the entire purpose of sharing the case online. Thus, the first step for any dermatologist wishing to use social media in the manner described above is to ensure that the local pathologist is able to properly process/section/stain skin biopsy specimens and is able to take high-resolution photomicrographs. One of the authors (J.M.G.) has shared an H&E staining protocol on his website.9 Methods to obtain high-resolution photomicrographs with only a smartphone have been described as well.3,4,10 It is important for the dermatologist or pathologist posting the case to recognize that comments or diagnostic ideas shared by other social media users are just that: comments and ideas only. They do not represent official consultation or medical advice in any way, and these online interactions do not establish formal doctor–doctor or doctor–patient relationships. The pathologist making comments or offering diagnostic ideas about a case is not receiving financial compensation for their work, nor do they even know the identity of the patient. Nonetheless, at least in the litigious USA, there is still some concern among pathologists (and other doctors) that discussing cases online could create a degree of legal risk for the pathologist. We are not aware of any medical malpractice lawsuits against pathologists that have arisen from conversations about difficult cases on Facebook, Twitter, or other social media sites. That does not entirely preclude the possibility, but it is our opinion that the legal risk is probably extremely small. Any such risk can likely be further reduced by the application of common sense and mutual professional courtesy. Pathologists can share useful diagnostic ideas and general principles without making firm and definitive diagnoses. It should also be remembered that making a comment or diagnosis about a case online does not make one a board-certified dermatopathologist; non-dermatopathologists, including junior trainees or even non-physicians, could potentially view and comment on posted cases. Dermatologists must use their own clinical judgment based on their own medical training and knowledge to make the best diagnosis and treatment decisions for their own patients. The dermatologist can gather useful ideas from discussions on social media, but the final medical care of the patient is solely their responsibility. Obviously, the names of pathologists who discuss ideas about a case on social media should never be recorded in a patient's medical chart or otherwise treated as though they were official consultants. There are other benefits to dermatologist and pathologist use of social media aside from just discussing difficult cases. In the past few years, there has been dramatic growth in the number of pathologists and dermatopathologists who use social media (especially Twitter). One of the authors (J.M.G.) maintains a list of pathologists and pathology-related Twitter accounts, which now numbers over 3000 (https://twitter.com/JMGardnerMD/lists/pathologists). Dermatopathology activity on Twitter is very robust; over a recent 6-month period, there were 33,403 #dermpath tweets made by 1973 users (an average of over 5500 #dermpath tweets per month) (Fig. 2).11 Most major pathology organizations in the United States now have a social media presence, including the American Society of Dermatopathology and the International Society of Dermatopathology.12,13 The American Academy of Dermatology and other dermatology organizations are also active on social media.14 Dermatology education-focused social media accounts, such as those of Dr. Josette McMichael (@globaldermie on Twitter and Instagram) provide excellent clinical images and information from the dermatologist's perspective (Fig. 3). Many university pathology and dermatology departments maintain social media accounts on Facebook and/or Twitter. Pathology journals use social media accounts to share newly published articles. There is even a dermatopathology online journal club (#dermpathJC) held monthly on Twitter for discussing and debating new dermatopathology literature.15 Live tweeting activity at pathology meetings has exploded since 2015, allowing pathologists, dermatologists, and other medical professionals from all over the world to stay up to date and to interact with attendees even if they cannot attend the meeting in person.16 Periscope, YouTube, and Facebook Live provide additional interactive venues for pathology and dermatopathology education.17 There has never been a better time for dermatologists from around the world to network with and learn from the pathology community online!FIGURE 2.: Twitter activity for the #dermpath hashtag over a 6-month period (11/7/2016–5/6/2017). Figure courtesy of Symplur.com.11FIGURE 3.: Social media can be used to share classic examples of dermatologic entities for educational purposes. Dr. Josette McMichael (@globaldermie on Instagram and twitter), an adjunct assistant professor of dermatology at Emory university in Atlanta, GA, USA, has a strong interest in global dermatology and education. She shares dermatology cases from around the world accompanied by useful teaching and discussion (https://twitter.com/globaldermie/status/763553059465297920).Networking and collaboration between pathologists and dermatologists around the world strengthens professional and personal bonds. Both of the authors have met numerous other pathologists and dermatologists online who we now count as close friends and colleagues despite living a world away from them and having never met them in person. Perhaps surprisingly, online interactions between professionals can lead to true friendships "in real life." One of the authors (J.M.G.) once posted on Facebook when his child was ill; he received wishes of recovery for his child from all over the globe, including from a physician in Tunisia (who had never met him in person) who sent him a video of a children's lullaby song to comfort his child. Such mutual respect and rapport among members of our specialties on a global scale can only bring about good will and appreciation of the work we all do not only in providing health care for our patients but also in balancing our work lives with our personal lives. This type of interaction has never before been possible on the scale that social media allows. Some may find it disconcerting, but in the experience of the authors, these interactions have led not only to real world friendships but also to great academic collaborations and professional networking. One of the authors (J.M.G.) has participated in multiple projects and peer-reviewed publications with coauthors from around the world that he has never met face to face; all of these collaborations and relationships were forged via Twitter and Facebook.5,6,18–21 In fact one needs look no further than the title page of this article you are reading to find evidence of the beneficial outcome of social media interactions; the 2 authors of this article have interacted many times on social media but have actually never met in real life. We live 13,000 km away from one another, and yet we are writing a paper together via the Internet, thanks to a professional relationship founded on Facebook. Distance is no longer a barrier to professional networking and collaboration between pathologists and dermatologists. We must embrace this technology and put it to good use for the benefit of our careers, our specialties, and most importantly, our patients.
Background: Metastatic melanoma in sentinel lymph nodes is often elusive to detect with morphology alone. Per American Joint Committee on Cancer staging guidelines, a single atypical melanocyte in lymph node qualifies as metastasis, whether identified by morphology or immunohistochemistry, but single cell staining must be convincing. We propose that the use of a second immunohistochemical run performed on a single slide will allow for more confident diagnosis of micrometastases. Materials and Methods: We designed a technical study to determine whether a second antibody application on previously stained slides can successfully detect the same population of cells. Melanocytic neoplasms were stained with SOX-10 using Ventana Benchmark Ultra stainers, coverslipped, and examined, followed by coverslip removal and application of MART-1 (Ventana A103). The order of antibody application and chromagen detection kit (AP-RED vs. DAB) was reversed to establish reliability and robustness of the protocol. Results: All melanocytes marked with SOX-10 and MART-1, and produced a range of staining quality that varied based on order of stain application and chromagen kit were used. The optimal combination was red MART-1 applied first followed by brown SOX-10 applied second. Conclusions: Consecutive staining of melanocytes with SOX-10 and MART-1 may improve diagnostic confidence of melanocyte identification, particularly in detection of single cell, micrometastases in sentinel lymph nodes or in situations where dual immunohistochemical stains may be unavailable.
