United States

Adenocarcinoma of the anus is a rare form of cancer, accounting for only 10% of primary anal carcinoma diagnoses. This case involves a 65-year-old female with an incidentally discovered anal mass. 

The patient was initially admitted for COPD exacerbation and iron deficiency anemia. On physical exam, the patient was found to have an anal mass at the 8 o’clock position. Further history revealed that she had experienced bleeding and painful defecation for the last 3 months. Subsequently, the patient underwent a left inguinal and anal node biopsy to determine tumor origin and progression. The mass was biopsied, and immunohistochemistry was performed. Staining demonstrated strong reactivity for cytokeratin 7 and focal reactivity for p16. These markers indicated an adenocarcinoma of anal origin. Diverting colostomy was performed to allow for wound healing and prevent further blood loss. She continues to be followed by oncology for further evaluation and treatment.

Clinically, the significance of distinguishing the origin of anal canal tumors is the mechanism of spread, which reflects the dual lymphatic drainage system. A colorectal adenocarcinoma carries an increased risk of spread via the inguinal and femoral nodal chains compared with a rectum-based adenocarcinoma. Histochemical staining with glands positive for cytokeratin 7 can be used to classify tissue as ductal or glandular in origin. However, the histological pattern of anal gland adenocarcinoma remains to be sharply defined, thus strengthening the need for further exploration within the literature. Further classification and understanding among multiple disciplines of medicine are pertinent to better treatments and prognosis in patients presenting with anal adenocarcinoma. 

Adenocarcinoma of the anal canal accounts for 2.7% of all gastrointestinal malignancies. The limited number of studies and discussions in the literature make it challenging as a pathological diagnosis and for appropriate clinical management. As more cases are reviewed, there is an increased opportunity for treatment development and prognosis improvement.

2022 AMA Research Challenge

Incidental Discovery of Advanced Primary Anal Adenocarcinoma

Welcome to the largest national, multi-specialty research event **featuring research from 750 medical students, residents and fellows, and international medical graduates.**


#### Event Details
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Ricardo Correa, MD, EdD
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Stuart M. Greenstein, MD
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Stephanie Strohbeen, MD
 
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Jessica Li, MD/PhD Candidate
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Charles Lopresto, DO

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Welcome to the largest national, multi-specialty research event featuring research from 750 medical students, residents and fellows, and international medical graduates.


poster

Background: Colorectal cancer is the second leading cause of cancer deaths in the United States. Synchronous cancers occur rarely, representing approximately 3.5% of all colorectal cancers. When compared to open colectomies, laparoscopy has been shown to have similar oncologic outcomes with shorter hospital stays and lower 30-day mortality. Additionally, intraoperative fluorescence angiography (IFA) provides an objective assessment of bowel and anastomotic perfusion.

Case Presentation: Here we present the case of a 74-year-old lady who had synchronous ascending and sigmoid colon adenocarcinomas, treated with a laparoscopic resection. She initially underwent a colonoscopy for evaluation of symptomatic anemia which revealed an ascending colon adenocarcinoma. The bowel prep was poor however, and repeat colonoscopy revealed a synchronous adenocarcinoma in the sigmoid colon. We performed a laparoscopic total abdominal colectomy with primary end-to-end ileorectal anastomosis and IFA with indocyanine green (ICG). The procedure was successfully completed laparoscopically. A total of 8 ports were used. The extraction site incision measured 6cm. IFA with ICG showed good perfusion of the small bowel conduit and ileorectal anastomosis. Final pathology revealed a right colonic well-differentiated pT2 adenocarcinoma (16.5cm proximal margin), a moderately differentiated pT2 distal sigmoid colon adenocarcinoma (7.5cm distal margin), and 48 benign lymph nodes. These findings represented an optimal oncologic resection with adequate lymph node harvest and margin status. The patient recovered well and was ready for discharge home on postoperative day 4 without need for narcotics. She continues to be well 4 months after surgery.

Discussion: Assessment for synchronous lesions is critical in the evaluation of colorectal cancer patients. This case highlights a rare case of synchronous colon cancers and exemplifies the advantages of laparoscopic technique. It also illustrates the utility of intraoperative bowel perfusion assessment with fluorescence angiography, which has been associated with lower anastomotic leak rates.


Minimally Invasive Treatment of Synchronous Colon Cancers

Background: 
Although Mycobacterium chelonae is ubiquitously found in the environment, cutaneous infections with M. chelonae are rarely reported. The few reported cases generally feature opportunistic infections in immunocompromised hosts. Due to its uncommon nature, providers often overlook this mycobacterium as the causative agent of a painful erythematous rash in their differential diagnosis. This case highlights common presentations and features of M. chelonae infection and demonstrates the importance of looking to ordinarily benign organisms as harmful and virulent in our immunocompromised population. 

Case Presentation: 
A 48-year-old female with refractory Behçet’s disease, maintained on methylprednisolone and apremilast, presented for a painful rash on her left lower extremity. She reported two months of tender nodules spreading from her ankle up to her medial thigh. Exam revealed erythematous and violaceous nodules in a sporotrichoid pattern. Three skin biopsies were performed over a period of two months; the first two were inconclusive, while the third showed marked dermal and subcutaneous inflammation with microabscess formation. Fite and AFB stains highlighted acid fast organisms. Subsequent acid-fast bacilli tissue culture grew M. chelonae.

The patient was initiated on triple antibiotic therapy with tobramycin, linezolid, and clarithromycin; however, her course was complicated by drug-induced liver injury. She was then transitioned to tobramycin and imipenem, leading to acute kidney injury and rhabdomyolysis. This prompted a final shift to imipenem and omadacycline, which was ultimately successful in resolving the rash.

Discussion: 
Although cutaneous infections with M. chelonae and other atypical mycobacteria are rare, providers should maintain a high level of suspicion in immunocompromised patients presenting with skin lesions, especially in a sporotrichoid pattern. Violaceous nodules in immunocompromised hosts should always warrant an infectious work-up. The diagnosis of atypical mycobacterial cutaneous infections in a timely fashion may be challenging. Multiple representative biopsies may be required for histopathological examination, which should include acid-fast staining, followed by routine bacterial and mycobacterial culture to achieve the most accurate diagnosis.


A Case of Atypical Mycobacterial Infection in a Patient with Bechet's Disease

Herpes genitalis caused by herpes simplex virus type 2 (HSV-2) is estimated to affect approximately 45 million adults in the United States. Over the past two decades, increasing HSV resistance to acyclovir has been noted among immunocompromised patients. HSV refractory to acyclovir is a complex clinical challenge with few alternatives available.

A 42-year-old woman with a past medical history of mycosis fungoides presented to the hospital with painful well-defined, edematous labial erosions that worsened from her previous admission. During this last admission, HSV-2 was detected on skin swabs via PCR from labia majora lesions. Punched-out discrete erythematous coalescing erosions were observed on the buttocks, groin, and proximal thighs, in addition to sloughing of the skin and grey-brown exudate. Initial therapy with intravenous (IV) acyclovir was transitioned to topical cidofovir cream and IV foscarnet due to suspected acyclovir resistance. Susceptibility testing confirmed acyclovir resistance and sensitivity to foscarnet. Despite improvement, foscarnet and cidofovir were discontinued due to dysuria and chemical burns, respectively. Our patient's decreased renal function made her a poor candidate for guideline-recommended IV cidofovir and high-dose acyclovir. Consequently, she was enrolled in a clinical trial for the novel antiviral priteliver. Hospitalization was further complicated by polymicrobial bacteremia, for which she was placed on continuous renal replacement therapy due to worsening acidosis and acute kidney injury. The priteliver was discontinued due to oliguria and worsening renal failure leaving the patient with no viable options. Given the severity of her lesions and concern for possible viral encephalitis, the infectious disease team determined that restarting treatment with IV foscarnet would outweigh the renal risks of therapy.

With the emergence of acyclovir-resistant HSV, clinicians must stay up to date with alternative treatments. The use of second-line agents, such as foscarnet and cidofovir, requires special consideration as these drugs are associated with higher toxicity. Unfortunately, foscarnet's nephrotoxicity complicated our patient's clinical course. Novel antivirals will provide better tools to tackle this clinical challenge. Priteliver is designed to inhibit viral replication by targeting the HSV helicase primase and is currently in an ongoing open-label trial to assess efficacy and safety in immunocompromised patients.

Acyclovir-resistant herpes simplex virus in a mycosis fungoides patient

While alopecia is common in patients with adrenoleukodystrophy (ALD), characterization of the hair loss pattern is poorly understood and is often reported as male androgenetic alopecia. In a previous case report, a scalp biopsy in an ALD patient diagnosed with androgenetic alopecia demonstrated sebaceous hypertrophy on H&E findings, with hair shaft structural abnormalities on scanning electron microscopy (EM), suggesting an an alternate alopecia mechanism. A 14 year old male with cerebral ALD presented to our institution with a clinical picture that matched a non-scarring alopecia, yet his scalp biopsy electron microscopy results were consistent with a non-inflammatory scarring alopecia. This case illustrates the variety of structural abnormalities underlying alopecia in ALD, and further research is needed to better understand the disease process.


Alopecia in a Pediatric Patient with Adrenoleukodystrophy

Background
Linear porokeratosis is a rare subtype of porokeratosis, a group of keratinization disorders. All porokeratosis disorders share the histopathological feature of a coronoid lamella, seen as columns of parakeratosis and dyskeratotic cells found in the granular layer of the epidermis. Linear porokeratosis presents in childhood with hyperkeratotic plaques, typically arranged in a unilateral linear formation that follow a Blaschko line distribution or dermatomes. Current therapies are reported to have unsatisfactory outcomes. Topical cholesterol 2%/ lovastatin 2% cream has been proven to be effective in some forms of porokeratosis, but has limited studies in the linear form. 

Case Presentation
A 61-year-old male presented to his family physician with erythematous plaques on the bilateral upper extremity of over 50 years duration. He has tried and failed standard treatment, including clobetasol, calcipotriene cream and diclofenac gel. Clinical presentation and pathologic examination of a skin biopsy revealing a coronoid lamellae were consistent with bilateral linear porokeratosis. Through a PubMed search, there have been limited reported cases of unilateral linear porokeratosis, but there have not been any reported cases of bilateral linear porokeratosis.

Discussion
A current theory for development is a two-hit mutation in the phosphomevalonate kinase (PVMK) and mevalonate diphosphate decarboxylase (MVD) genes of the cholesterol synthesis pathway, causing loss of function of the genes. These mutated genes inhibit the cholesterol synthesis pathway. Because cholesterol is an essential factor in the overall health of the stratum corneum, cholesterol depletion causes premature apoptosis of the keratinocytes, leading to the formation of the porokeratosis. 
The compounded cholesterol 2%/lovastatin 2% ointment provided a profound decrease in the hyperkeratotic scaling and erythema associated with our patient’s bilateral linear porokeratosis. After a 12 week trial, the overall size of the patches and plaques were significantly reduced in the treated areas. The mechanism of action of the targeted therapy and the results our patient achieved support the two-hit mutation theory (loss of function mutations in PVMK and MVD) in causing of linear porokeratosis. Cholesterol and lovastatin have an established safety profile and offers a relatively inexpensive alternative treatment option that may have better outcomes than current standard therapies. 


Bilateral Linear Porokeratosis Treated with Topical Cholesterol 2%/ Lovastatin 2%

“CHRONIC WOUND MANAGEMENT AND SOCIOECONOMIC BARRIERS IN A STREET MEDICINE SETTING”
Jesse Obregon, Taha F. Rasul, Brittany J. Blake, Orly Morgan, Julie Schnur, Armen Henderson
Miami Street Medicine Institute, University of Miami Miller School of Medicine


Background
Persons experiencing homelessness (PEH) have decreased access to longitudinal care which means that they often present to providers in advanced disease stages. Street Medicine providers in low resource settings should consider cost-effective methods of managing patients with chronic wounds in order to prevent the development of complications. We present two cases in which Street Medicine providers used physical exam findings and a multifaceted approach to manage chronic wounds of differing etiologies. 
Case Presentation
Patient 1: A 53-year-old male was seen with multiple, acute and chronic facial wounds. He had been hospitalized multiple times in the past year due to seizure activity. He had been prescribed Levetiracetam, however did not take the medication due to side effects and limited access to refills. 
The street medicine team provided wound care, counseled on medication adherence, and coordinated an appointment at a nearby low-income clinic. Two weeks later, he had refilled his medication and did not have any further facial or bodily trauma. 
Patient 2: A 65-year-old unsheltered male with a history of liver disease was encountered for left leg non-healing ulcer. He was hesitant to receive care at any clinical setting. Initially, the wound was approximately 12 x 9 cm in size with purulent drainage and foul odor. Wound care provided consisted of saline irrigation, gentle debridement, bandaging, and multivitamin tablets. He was also provided with wound care supplies for self-service. Over the next 6 months, his wound shrunk to 8 x 7.5 cm in size with the presence of granulation tissue without erythema or malodorous discharge.

Discussion
The first case demonstrates how monitoring facial wound healing processes served as a clinical marker of seizure disorder improvement. Connecting that patient to primary care by leveraging community resources and medication refills helped in the improvement of his seizure disorder. The second case provided a challenge as the patient was resistant to help for his wound care and medical condition. Consistent wound care likely decreased the risk of severe complications such as cellulitis, osteomyelitis, and abscesses. Street medicine organizations can serve as a bridge for PEH from the street to the clinical setting. 


Chronic Wound Management And Socioeconomic Barriers In A Street Medicine Setting

Cutaneous Mycobacterium abscessus infection following injection of a lipolytic agent

Background: Nevus Sebaceous (NS) is a congenital hamartoma characterized by orange to skin-colored verrucous plaques typically of the scalp, face, forehead, or neck. Numerous publications report cases of secondary neoplasms arising from NS plaques including trichoblastoma, syringocystadenoma papilliferum, and basal cell carcinoma. In some exceptional cases, poroma–adnexal tumors of the intraepidermal sweat gland duct–have been reported to arise in NS plaques. 
Case Presentation: A 56-year-old man presented to the dermatology clinic with a brown pedunculated verrucous plaque overlying scattered irregularly shaped dark-brown plaques. The pedunculated plaque was biopsied for histopathological evaluation and showed benign adnexal neoplasm with eccrine differentiation most consistent with a pigmented eccrine poroma. A wide-local excision for complete lesion removal and further histologic examination was performed. The second biopsy revealed focal areas of acanthosis and papillomatosis with sebaceous gland hyperplasia consistent with nevus sebaceous. 
Discussion: Upon literature review, there are seven documented cases of poroma growth within a NS, four of which are eccrine poromas. In comparing cases, clinical differences including distinct morphologies of NS and EP plaques, and coexisting neoplasms can be observed. To this degree, our case might offer insight into the unique and rare presentation of secondary EP plaques arising from primary NS lesions. 


Eccrine Poroma Arising within a Nevus Sebaceus

Background
Harlequin sign is a rare disorder of the sympathetic nervous system with a noteworthy clinical presentation. Disruption of T2-T3 sudomotor and vasomotor innervation manifests as a unilateral facial paleness and anhidrosis with compensatory flushing and hypersudation contralateral to the site of injury. Horner’s syndrome is commonly associated, which involves interruptions to the T1 oculomotor sympathetic neurons resulting in ptosis, pupil constriction, and lack of sweating ipsilaterally. Recognition of these clinical presentations is essential in determining appropriate workup. 

Case Presentation
An 81-year-old female with a history of metastatic lung cancer presented with right-sided flushing predominantly in a V1 and some V2 dermatomal distribution, sharply demarcated at the midline. Notably, the patient also had left pupillary miosis and left partial ptosis, although no asymmetric anhidrosis. Her review of systems was negative for pruritus, pain, tingling, burning, blistering of the skin, which argues against zoster. She denied any neuropathic symptoms, changes in vision, flushing when eating, or prior procedures to the face that might otherwise suggest Frey syndrome. Given the clinical findings, this condition was likely secondary to a mass effect from a left upper lobe lung tumor, which measured 11.0 cm with encasement of the left common carotid artery and posterior elements of T1 and T2 segments on MRI. The patient continued treatment for her underlying malignancy and her symptoms improved.

Discussion
Diagnosis relies on a thorough medical history and physical exam. A brief exercise test or heat exposure can also induce symptoms in the clinic. Cervical MRI scans may further elucidate the primary cause, which can be idiopathic, congenital, iatrogenic, or organic, such as surgical procedures or a mass in the cervical region. Thus, the underlying primary cause should be the focus for treatment management and symptoms may subsequently resolve on their own. Interventions such as botulinum toxin injections or sympathectomy can be recommended if flushing or sweating negatively affects social life. Although this patient already had a known history of malignancy, such cutaneous signs may manifest as the first presenting sign of internal disease and should prompt physicians to assess for the underlying etiology and consider imaging to rule out malignancy.


Harlequin Sign Associated with Horner's Syndrome

Histopathologic analysis of debulk specimens in Mohs micrographic surgery (MMS) may augment high-risk factor identification in cutaneous squamous cell carcinoma (cSCC), leading to tumor upstaging. Existing studies have yet to comment on the location of high-risk factors within tumors. Herein we report four cSCCs initially categorized as well-differentiated that were reclassified to moderate to poorly differentiated on debulk analysis and upstaged accordingly. In all cases, the deep tumor margins displayed morphological differences from other areas, exhibiting less differentiation and/or perineural invasion. Thorough inspection of the deep tumor margins may be required for accurate tumor staging and evaluation of metastatic risk. 

Case Series
Patient 1: An 80-year-old male presented with a 2 cm plaque on the frontal scalp. Biopsy revealed well-differentiated cSCC staged at T2a with Brigham and Women’s Hospital Staging System (BWH), subsequently upgraded to T2b during MMS due to galea involvement. Debulk analysis revealed moderate to poorly differentiated cSCC with the least differentiated cells at the deep margin.
 
Patient 2: A 75-year-old male presented with a 2 cm plaque on the left vertex scalp. Biopsy revealed well-differentiated cSCC staged at T2a (BWH), subsequently upgraded to T2b during MMS due to extension beyond subcutaneous fat and PNI. Examination of the second stage revealed moderately differentiated cSCC with the least differentiated cells at the deep margin.
 
Patient 3: An 86-year-old female presented with a 2.4 cm nodule on the right lower leg. Biopsy revealed well-differentiated invasive cSCC. Debulk analysis revealed moderately differentiated cSSC with the least differentiated cells at the deep margin.

Patient 4: An 82-year-old male presented with a 2.7 cm nodule on the vertex scalp. Biopsy revealed well-differentiated cSCC staged at T2a (BWH), subsequently upgraded to T2b during MMS due to extension beyond subcutaneous fat. Debulk analysis revealed moderate to poorly differentiated cSSC with the least differentiated cells at the deep margin in the galea.

cSCCs may exhibit intratumor heterogeneity in which predominantly well-differentiated tumors contain focal areas of poorer differentiation. Intratumor heterogeneity complicates tumor risk estimation as a well-differentiated tumor on biopsy may exhibit poor differentiation at a deeper margin. Thus, the most clinically relevant cells for prognosticating risk may not be visible on biopsy, underscoring the utility of close examination of the debulk specimen and deep margin of the Mohs layer. Despite this, most Mohs surgeons endorse immediately discarding debulk specimens without evaluation. These cases reinforce that tumor staging is incomplete until the deep margins are assessed to find the most dysplastic cells.

Incidental Discovery of Advanced Primary Anal Adenocarcinoma

Next from 2022 AMA Research Challenge

Minimally Invasive Treatment of Synchronous Colon Cancers

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