United States

Background: Mammary Paget’s Disease (MPD) of the nipple-areolar complex (NAC) is a rare disorder of the breast associated with an underlying carcinoma affecting 1-4% of breast cancer patients. The etiology of MPD is thought to arise from a malignant conversion of pluripotent keratinocyte stem cells or cells of apocrine gland ducts; that is supported by structural similarity between Paget and Toker cells – epithelial cells found in the NAC of 10% of women. MPD presents as eczematous patches of scaly tissue surrounding the NAC associated with tingling and pruritis. 

Case Presentation: Here we describe a 74-year-old patient with local recurrence of breast cancer &gt;20 years following treatment. She initially presented with a right breast stage IA (cT1cN0M0) invasive ductal carcinoma involving right upper inner quadrant in year 2000. She was treated with partial mastectomy (PM) and sentinel lymph node biopsy (SLNB) followed by adjuvant whole breast radiation therapy and 2.5 years of adjuvant tamoxifen. She remained disease free until year 2022 when she presented with waxing and waning four-month history of skin irritation involving the right nipple. Exam demonstrated a small, 1 centimeter (cm), crusty erythematous rash. Initial trial of antibiotics did not improve symptoms. She underwent a punch biopsy which demonstrated MPD. Breast MRI showed a right NAC enhancement with a 0.5 cm mass at 12:00 o’clock position. Biopsy of the central mass demonstrated a grade 2 invasive ductal carcinoma, ER/PR+ without HER2 amplification. She underwent right mastectomy with SLNB with final pathology demonstrating stage IA disease (pT1apN0[sn]). 

Discussion: This case highlights a unique clinical sign for breast cancer recurrence despite a long period of remission. Several factors are associated with a high risk of late recurrence including ER+ tumors, diagnosis before the age of 40, treatment involving breast conserving surgery, 4 or more positive lymph nodes, and a T2 or higher tumor stage. It is challenging to know if the new breast cancer is recurrent or new primary, although management is similar. For patients with underlying malignancy, the rate of SLNB was 17% warranting nodal evaluation. MPD local recurrence has been shown to be common in patients who previously underwent nipple sparing mastectomy. Small, single institution, series found that patients with underlying MPD had worse survival compared to those without MPD. Unfortunately, no high quality, prospective, data exist to guide management for patients with MPD versus non-MPD recurrence; general approach includes SLNB followed by mastectomy; an alternative approach to mastectomy in women who recur a decade or two after initial PM and adjuvant radiation who are averse to mastectomy would be to repeat PM followed by partial breast radiotherapy. This case emphasizes the importance of early cancer surveillance to prevent delays in intervention.


AMA Research Challenge 2023

Mammary Paget’s disease of the nipple as a sign of local recurrence two decades after properly treated breast cancer

Background: Mammary Paget’s Disease (MPD) of the nipple-areolar complex (NAC) is a rare disorder of the breast associated with an underlying carcinoma affecting 1-4% of breast cancer patients. The etiology of MPD is thought to arise from a malignant conversion of pluripotent keratinocyte stem cells or cells of apocrine gland ducts; that is supported by structural similarity between Paget and Toker cells – epithelial cells found in the NAC of 10% of women. MPD presents as eczematous patches of scaly tissue surrounding the NAC associated with tingling and pruritis. 

Case Presentation: Here we describe a 74-year-old patient with local recurrence of breast cancer >20 years following treatment. She initially presented with a right breast stage IA (cT1cN0M0) invasive ductal carcinoma involving right upper inner quadrant in year 2000. She was treated with partial mastectomy (PM) and sentinel lymph node biopsy (SLNB) followed by adjuvant whole breast radiation therapy and 2.5 years of adjuvant tamoxifen. She remained disease free until year 2022 when she presented with waxing and waning four-month history of skin irritation involving the right nipple. Exam demonstrated a small, 1 centimeter (cm), crusty erythematous rash. Initial trial of antibiotics did not improve symptoms. She underwent a punch biopsy which demonstrated MPD. Breast MRI showed a right NAC enhancement with a 0.5 cm mass at 12:00 o’clock position. Biopsy of the central mass demonstrated a grade 2 invasive ductal carcinoma, ER/PR+ without HER2 amplification. She underwent right mastectomy with SLNB with final pathology demonstrating stage IA disease (pT1apN0[sn]). 

Discussion: This case highlights a unique clinical sign for breast cancer recurrence despite a long period of remission. Several factors are associated with a high risk of late recurrence including ER+ tumors, diagnosis before the age of 40, treatment involving breast conserving surgery, 4 or more positive lymph nodes, and a T2 or higher tumor stage. It is challenging to know if the new breast cancer is recurrent or new primary, although management is similar. For patients with underlying malignancy, the rate of SLNB was 17% warranting nodal evaluation. MPD local recurrence has been shown to be common in patients who previously underwent nipple sparing mastectomy. Small, single institution, series found that patients with underlying MPD had worse survival compared to those without MPD. Unfortunately, no high quality, prospective, data exist to guide management for patients with MPD versus non-MPD recurrence; general approach includes SLNB followed by mastectomy; an alternative approach to mastectomy in women who recur a decade or two after initial PM and adjuvant radiation who are averse to mastectomy would be to repeat PM followed by partial breast radiotherapy. This case emphasizes the importance of early cancer surveillance to prevent delays in intervention.


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Background: Mucinous Carcinoma of the breast is a rare subtype. It accounts for about 2% of all breast carcinomas. Mucinous Carcinomas are often mistakenly diagnosed as benign tumors. It is important to recognize the overlapping benign clinical, mammographic, sonographic and magnetic features to avoid delayed diagnosis.

Case Presentation: A 65-year-old African American woman presented with a palpable mass on her left breast. The patient had no family history or personal history of breast cancer prior to this appointment. The patient underwent a mammography, where the patient’s palpable mass was displayed as a high-density mass with well-defined margins. After the mammography, the patient had undergone both a breast MRI and an ultrasound guided biopsy, (which involved a biopsy marker clip in the palpable mass). The breast MRI showed the palpable mass with high signal intensity on T2 weighted imaging, and benign appearing kinetics. However, from the ultrasound guided biopsy, it was shown that the patient had Mucinous Carcinoma of the breast. After treatment, the patient chose to receive a mastectomy. 

Discussion: Mucinous Carcinoma of the breast is a rare subtype of breast cancer that typically occurs in women over 60 years old. It typically presents as a lump or mass in the breast. Mucinous Carcinomas tend to be larger in size compared to other breast cancers at the time of diagnosis. They often have well-defined borders and can be mobile within the breast tissue. Diagnosis of Mucinous Carcinoma of the breast typically involves imaging tests, such as mammography, and or ultrasound, along with a tissue biopsy. On mammography, ultrasound and magnetic resonance imaging (MRI), Pure Mucinous subtype presents as a well-circumscribed mass and, therefore, can be confused with a benign lesion. On MRIs, Pure Mucinous Carcinoma of the breast has higher diffusion coefficient values and therefore presents as high signal intensity T2-weighted imaging and benign-appearing kinetics with persistent enhancement. These MRI features could be difficult to distinguish from benign lesions, such as cysts fibroadenomas or intramammary lymph nodes and can often result in a delayed diagnosis. Knowledge of this is necessary because delayed diagnosis can lead to poorer health outcomes and health disparities in the future.


Mucinous Carcinoma of the Breast in a 65-Year-Old Woman

This clinial vignette explores the critical issue of uterine hemorrhagic rupture in cornual ectopic pregnancies, a rare but life-threatening condition. Cornual ectopic pregnancies are challenging to diagnose due to their location and can result in severe hemorrhage and hypovolemic shock if not detected early. This case presentation highlights the urgent need for prevention and intervention in such cases. This case also emphasizes the importance of considering social determinants of health, such as insurance and access to prenatal care, in patient care and research, as they can impact the course and outcomes of such conditions.

Uterine Hemorrhagic Rupture in Cornual Ectopic Pregnancy​

Case Presentation
A 2 year old female, ex-34 week preterm with a relevant family history of a male sibling with TTD and birth history of a TTD diagnosis, presents to the emergency department with feeding intolerance and episodic vomiting. Serially performed MRIs at 4 weeks old (corrected age of term birth) and 2 years old demonstrates progression of the condition. T1-weighted imaging presents with enlarged ventricles and significant hypointensity in areas of expected myelination. T2-weighted imaging displays significant hyperintensity in those same areas, suggestive of dysmyelination. Simplified gyral patterns were also observed. One week after the MRI, the patient had an overnight coughing episode resulting in her death, despite resuscitation efforts.

Discussion
TTD is a rare condition with a poor prognosis in children under 10 years old––a 20-fold higher risk of mortality than the general population, especially succumbing to infection. MRI performed on neonates as early as full term exhibits signs of dysmyelination in key structures such as the posterior third of the posterior limb of the internal capsule, ventrolateral nucleus of the thalamus and the optic radiations. Until 2 years of age, analysis of myelination of key structures can help monitor proper brain development. When physicians observe cortical atrophy and diffuse dysmyelination on MRI along with significant birth history, TTD should be included in the differential diagnosis.

From a Radiological Perspective: Progression of Trichothiodystrophy
in a Pediatric Case

Background
Intracranial pseudoaneurysms (IPAs) are rare in of themselves, accounting for <1% of all intracranial aneurysms, but have been reported at a higher incidence in the pediatric and adolescent population. If left untreated, the mortality rate of these lesions can reach up to 50% due to rupture and catastrophic intracranial hemorrhage. Therefore, early recognition and treatment of this condition in the pediatric population is essential to prevent further morbidity and future mortality.
In contrast to adult IPAs, pediatric IPAs account for up to one-third of all pediatric intracranial aneurysms and have different clinical presentations, complications, and treatment outcomes. Children do not possess the typical risk factors associated with intracranial aneurysms of adults, which should prompt further investigation into a cause for vessel wall injury. Potential etiologies include underlying vasculopathies, indicated in one tenth of pediatric cases; infectious agents; and extrinsic insults, such as head trauma. Pediatric IPAs can present with intracranial hemorrhage, with associated symptoms of sudden onset headache, seizures, vomiting, or loss of consciousness.
In contrast to adults, pediatric patients have a higher frequency of complex-appearing, large (i.e. 15-25 mm in diameter) or giant (i.e. >25 mm in diameter) IPAs, overall contributing to greater involvement of surrounding intracranial structures. Local mass effect due to these lesions can lead to intracranial complications, such as acute infarction or hydrocephalus.

Case Presentation
A 13-year-old with a family history of intracranial neoplasm presented with persistent headaches for a few months. Noncontrast MRI brain showed a large, mass lesion involving the right basal ganglia. The subsequently performed MRA brain and postcontrast MR imaging further characterized this lesion as a giant right MCA pseudoaneurysm. Local mass effect from the lesion on the foramen of Monro resulted in lateral ventricular enlargement. Right frontal encephalomalacia was also seen, presumably reflecting additional sequelae of prior vascular injury. Surgical intervention was performed soon after patient presentation.

Discussion
According to the ACR Appropriateness Criteria for pediatric headaches, imaging is not routinely indicated for primary headaches. In contrast, CT or MR imaging is usually appropriate for secondary headaches in pediatrics. Differentiation of primary and secondary headaches in children is clinically challenging. Clinicians should maintain a high level of suspicion for concerning symptoms and risk factors in pediatric patients, which would warrant an imaging assessment. While rare, IPAs are an important differential consideration to remember as definitive treatment is available and can help reduce future patient morbidity and mortality.

Pediatric Intracranial Pseudoaneurysms

Background
Autoimmune tracheitis is a rare condition where the immune system attacks the lining of the trachea, causing inflammation and swelling. It can lead to symptoms such as chronic cough, hoarseness, difficulty breathing, and, in rare cases, hemoptysis. The exact cause of autoimmune tracheitis is unclear, but it is thought to involve genetic and environmental factors. Diagnosing the condition can be challenging due to its rarity and overlapping symptoms with other respiratory conditions. 

Case Presentation
We present the case of an 82-year-old female with a history of well-controlled rheumatoid arthritis on methotrexate and a chronic tracheostomy inserted in childhood for vocal cord paralysis . The patient presented to the emergency department with a 6-month history of hemoptysis, weight loss, and loss of appetite. Physical examination and chest X-ray did not reveal any notable findings. Chest CT scan showed circumferential thickening of the mid trachea, including diffuse involvement of the posterior tracheal membrane. This area was also avid on PET scan, suggestive of ongoing inflammation. Rigid bronchoscopy revealed tracheitis and diffuse thickening of tracheal mucosa, resulting in severe narrowing of the tracheal lumen.
Biopsy results from the procedure were negative for malignancy but demonstrated the presence of plasma cells, complement deposition, and immunoglobulins suggestive of an autoimmune etiology. There was no evidence of granulomas and Congo Red Stain for amyloidosis was also negative. Microbiology, including Acid Fast Bacilli cultures, were negative as well.
Extensive autoantibody testing was performed to identify possible autoimmune conditions, and other than elevated rheumatoid factor, testing was unrevealing. Therefore, clinical diagnosis of autoimmune tracheitis was established. Treatment was initiated with prednisone therapy, followed by infusion of Adalimumab. The prednisone dosage was gradually tapered over time, and repeat bronchoscopy showed significant reduction of inflammation. During a six month follow up period, the patient remains asymptomatic. .


Discussion
Autoimmune tracheitis presents a significant diagnostic and management challenge due to its rarity and lack of specific criteria. There is paucity of literature on this topic. Guttman et al described a patient with Crohn's disease who developed tracheal cartilage inflammation successfully treated with anti TNF therapy. To our knowledge this is the first case report of autoimmune tracheitis in a patient with rheumatoid arthritis. It is important to be aware of this condition in patients with autoimmune disorders presenting with respiratory complaints.

A Rare Case of Autoimmune Tracheitis In A Patient With Rheumatoid Arthritis Successfully Treated With TNF-a Inhibitor

Background
Antisynthetase syndrome is a rare idiopathic inflammatory myopathy characterized by myositis, interstitial lung disease (ILD), arthritis, Raynaud’s phenomenon, mechanic’s hands, and antibodies against aminoacyl-transfer RNA synthetase, most commonly anti-Jo1 antibody.

Case Presentation
A 36-year-old Hispanic female with no known past medical history presented to the emergency department for 1 week history of left calf pain. She was diagnosed with unprovoked left popliteal vein thrombosis and was discharged on rivaroxaban. She returned the following day for dyspnea and chest pain. She had stable vital signs with adequate oxygenation at room air. Lung auscultation revealed clear breath sounds. Bloodwork showed mild leukocytosis and elevated CK, AST, ALT, and LDH. CT pulmonary angiogram (CTPA) was negative for pulmonary embolism but revealed large infiltrates in bilateral lower lung fields with small bilateral pleural effusions. Ground-glass infiltrates on bilateral upper and lower lobes were seen on high resolution chest CT. Infectious workup for pneumonia was negative. Further questioning revealed a history of two first trimester miscarriages, eczematous skin lesions, and bilateral knee pain. Rheumatologic workup was pertinent for elevated ESR and CRP and positive anti-Ro antibody. ANA, anti-dsDNA, anti-Scl-70, anti-RNP, anti-Smith, anti-cardiolipin, B2-glycoprotein, and lupus anticoagulant were negative. She was started on warfarin for possible antiphospholipid syndrome and steroids for ILD. Four months later, she had worsening dyspnea along with fever and proximal muscle weakness in bilateral lower extremities requiring hospital readmission. CTPA showed progression of bilateral upper and lower lobe ground-glass infiltrates. EMG-NCV was normal. Lung biopsy showed interstitial fibrosis and muscle biopsy of the left vastus lateralis revealed necrotizing autoimmune myopathy. Further rheumatologic workup was significant for positive IgM anticardiolipin and anti-PL-7 antibody but negative anti-Jo1 antibody. Based on the finding of ILD, myositis, and positive anti-PL-7 antibody, a diagnosis of antisynthetase syndrome was made. She continued steroid therapy and started mycophenolate. She had either inadequate control or experienced side effects of the various immunosuppressants. She had tuberculosis while on mycophenolate, myositis flares while on azathioprine, and rhabdomyolysis while on tacrolimus. Her course was complicated by cardiac myositis, and she received intravenous immunoglobulin and rituximab. She was stable on discharge with plans for further infusion, but she died a few weeks later from respiratory failure.

Discussion
Diagnosis of antisynthetase syndrome is based on clinical features and presence of aminoacyl-transfer RNA synthetase antibody, and treatment consists of immunosuppressive therapy. This case illustrates the complexity of diagnosis, often requiring a multi-disciplinary approach, and the difficulty to control symptoms.

Anti-PL-7 Antibody Positive Antisynthetase Syndrome

Background
Systemic lupus erythematosus (SLE) is a chronic, multi-systemic autoimmune disorder that presents in a myriad of ways. However, lupus enteritis is a rare initial manifestation. 

Case Presentation
A 30-year-old female with PMH DM2 and obesity presented with periumbilical pain for one day associated with nausea, NBNB vomiting, and fatigue. She denied rashes, skin changes, fever, arthralgias, oral ulcers or hair loss. On examination, temperature 97.7°F, BP 138/69, HR 121, RR 22, and O2 saturation 99% on room air; bowel sounds were normal and there was diffuse abdominal tenderness and distension without rebound/guarding. Notable labs included creatinine 1.2 and a urinalysis showing protein 300, RBCs (6-10), and protein/creatinine ratio 2304. A CT abdomen revealed moderate ascites and an approximately 42 cm segment of moderate small bowel wall thickening, predominately of the proximal jejunum, concerning for infectious or inflammatory enteritis. Ascitic fluid studies revealed SAAG <1.1 g/dL. A subsequent MRI abdomen showed possible mid-small bowel obstruction and targetoid mucosal and serosal enhancement. The obstruction was managed conservatively with NGT placement; however, her abdominal pain persisted even though she had bowel movements and had no radiographic worsening of the obstruction. During the hospitalization, her renal function did not improve; an autoimmune work-up revealed positive ANA, dsDNA, anti-smith Ab, RNP Ab, chromatin Ab, ribo protein IgG, and SM RNP Ab; C3 and C4 complement levels and serum albumin were low. She was transferred to a tertiary care center and a kidney biopsy revealed Class III lupus nephritis. She was started on pulse-dose steroids and hydroxychloroquine. She improved clinically, her renal function improved and she was discharged home on azathioprine, hydroxychloroquine and prednisone.

Discussion
SLE can affect numerous systems but rarely involves the gastrointestinal system as an initial manifestation. Lupus enteritis is only present in about 0.2 – 5.8% of cases with SLE. It is thought to be related to immune complex deposition and complement activation leading to submucosal bowel wall edema and mostly affects the Jejunum and the Ileum. The clinical presentation is often nonspecific, however frequent complaints include abdominal pain, nausea, and vomiting. CT abdomen/pelvis is the diagnostic modality of choice as pathology is low yield. Common imaging features include Target sign, Combs sign, Mesenteric fat stranding and ascites. Due to its rarity, there are no established guidelines for management, however prior case reports have demonstrated a positive response to steroids.



Lupus Enteritis: An Uncommon Manifestation of Systemic Lupus Erythematosus that Coalesced with Cryptogenic Lupus Nephritis

Background
Carcinoid tumors are masses originating from neuroendocrine cells and are one of the rarest forms of endocrine cancer. Minimal literature exists regarding neuroendocrine tumors arising from the mediastinum, let alone the thymus. This is likely secondary to its rarity, with a reported incidence of 0.2 per million in the United States.
Case Presentation
When diagnosing a neuroendocrine tumor, it is crucial to distinguish the combined neuroendocrine and epithelial characteristics of the neoplasm, acknowledge its potential aggressiveness, and establish additional markers for prognosis and prediction. In the following review, we present a case of a 64-year-old male with an incidental finding of an atypical thymic neuroendocrine tumor. A radical robotic-assisted thymectomy was performed, and adjuvant radiotherapy was administered. 
Discussion
Atypical thymic neuroendocrine tumors remain a niche disease, presenting a unique challenge due to rarity, diverse characteristics, and aggressiveness. Though lacking consensus or best-practice guidelines, surgery is considered the most curative treatment modality. Proving the variability of this type of tumor, however, radiation therapy has had unclear and inconsistent effects on long-term survival, either enhancing clinical outcomes or failing to improve 5-year survival rates. Overall, survival rates for thymic neuroendocrine tumors are lower than those of the gastrointestinal tract, highlighting the need for better therapeutic strategies to maintain the highest level of care for such patients.

Thymic Atypical Carcinoid Tumors vs. Gastrointestinal Neuroendocrine Tumors - 
Are They Really the Same Disease?

Xp11 translocation renal cell carcinomas (RCC) are a category of RCCs
that involve translocations of the chromosome Xp11.2, which is
responsible for generating fusions of transcription factor E3 (TFE3).
These malignancies encompass the most prevalent type of RCC in the
pediatric population, while in adults, Xp11 RCCs account for merely 1-
4% of renal malignancies.
We detail the case of a 68-year-old male who presented to the
emergency department after a ground-level fall with a small forehead
laceration. As part of his work-up, a non-contrast CT abdomen/pelvis
was obtained, on which a 3.9 x 4.5cm left posterior mid-pole renal mass
was noted, suspicious for an RCC. Further workup confirmed an
enhancing posterior left renal mass with no evidence of metastatic
disease. Histopathological and genetic analysis of the extirpated mass
was notable for a Xp11 translocation RCC, pT1bNXMX Fuhrman Grade 2,
with negative margins. Considering the patient had no local invasion or
metastasis, he was discharged and scheduled for surveillance imaging.
Overall, Xp11.2 RCCs in the elderly population are uncommon. Genetic
and IHC analysis is essential in providing accurate and timely diagnoses
of RCCs of this subtype. Since prognosis of this neoplasm in adults is
worse than in pediatric patients, awareness of adequate interventions
and diagnostic tools is of the utmost importance in order to improve
patient outcomes.

68 Year-Old Male with Rare Xp11 Translocation Renal Cell Carcinoma


Background: Testicular infarction is a rare complication of epididymitis. We present a case of testicular infarction to highlight this complication and the role of ultrasound in aiding diagnosis to guide management.

Case Presentation: 26-year-old male, with recent admission for left epididymitis secondary to Multiple Drug Resistant Enterobacter, presented to the emergency department with a two-day history of progressively worsening left scrotal pain and swelling. Physical examination revealed left scrotal erythema and tenderness. Scrotal ultrasound demonstrated asymmetric enlargement and heterogeneous appearance of the left testicle consistent with left scrotal edema. The left testicle showed peripheral hypervascularity without intrinsic flow on color and spectral Doppler interrogation compatible with testicular infarction. In contrast, the right testicle was homogenous and with normal arterial and venous spectral Doppler flow. Management included intravenous antibiotic and urology consultation with subsequent partial orchiectomy. Patient’s hospital course was complicated by wound dehiscence and residual necrotic tissue requiring scrotal debridement and washout. After transition to oral antibiotics, he was discharged with outpatient follow-up with urology.

Discussion: Ultrasound with color flow Doppler is the primary method to diagnose testicular infarction secondary to epididymitis. Characteristics of testicular infarction include asymmetrically decreased or absent intrinsic testicular blood flow with or without increased peripheral flow. Although understanding of the pathophysiology of testicular infarction is evolving, arterial and venous insufficiency are suspected. Risk of global testicular infarction is low due to the testes receiving blood supply from the testicular, the deferential and cremasteric arteries. Persistent clinical symptoms and worsening imaging findings can warrant surgical intervention. In addition to spectral and color doppler, there is expanding utilization of contrast- enhanced sonography (CEUS) to increase sensitivity for testicular infarction. Testicular infarction is a rare but important diagnosis to consider in the setting of epididymitis that has management implications to prevent morbidity.

Next from AMA Research Challenge 2023

Mucinous Carcinoma of the Breast in a 65-Year-Old Woman