Title: Pembrolizumab-Induced Epidermotropic CD8+ Dermatitis in a Patient with Multiple Squamous Cell Carcinomas

Background:
Pembrolizumab, a programmed death-1 (PD-1) inhibitor, has been increasingly associated with dermatologic immune-related adverse events (irAEs), varying from benign rashes to severe conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. While the literature describes various dermatologic manifestations like lichenoid dermatitis and granuloma annulare as pembrolizumab side effects, we report a distinctive case of pembrolizumab-induced epidermotropic CD8+ dermatitis in a patient with a history of multiple squamous cell carcinomas (SCCs) and a keratin-positive malignant spindle cell neoplasm. This case adds to the evolving spectrum of pembrolizumab's dermatologic irAEs, underscoring the need for vigilance in patients receiving immune checkpoint inhibitors (ICIs).

A 69-year-old female with a history of multiple SCCs treated across various anatomical sites presented with complaints of a widespread rash. The patient reports that the rash had persisted for 20-30 years but had notably worsened following the initiation of pembrolizumab treatment two years prior. Pembrolizumab was administered as part of her treatment regimen for a keratin-positive malignant spindle cell neoplasm of the right proximal femur. She described the rash as intensely pruritic, worsening during winter months, with mild improvement during summer.

Methods:
Compiled through a retrospective review of medical records with patient consent. Diagnostic assessments were conducted using standard histological and immunohistochemical techniques, supplemented by PCR for T-cell receptor gene rearrangements to evaluate T-cell clonality.

Results
On skin examination, extensive coalescing, ill-defined erythematous patches with associated xerosis were observed. A biopsy of an eczematous lesion on the left lower back was performed to further investigate the rash's etiology. Histopathological analysis revealed hyperkeratosis, parakeratosis, and infiltration of epidermotropic lymphocytes within the epidermis. The infiltrate was predominantly composed of CD8+ T cells. Further molecular studies were negative for clonal T-cell receptor rearrangements.

Conclusion
Given the lack of T-cell clonality and the CD8+ cell-rich infiltrate, a diagnosis of pembrolizumab-induced epidermotropic CD8+ dermatitis was favored over other dermatologic conditions such as mycosis fungoides. The chronicity and the pre-existing nature of the rash, coupled with the exacerbation post-pembrolizumab therapy, underscore its drug-induced origin, distinct from typical dermatologic irAEs reported with ICIs. This case is particularly unique due to the uncommon histopathological feature of epidermotropism of CD8+ T cells, divergent from the more common CD4+ presentations seen in other cases of pembrolizumab-induced dermatitis.

The patient continued with pembrolizumab therapy for her underlying malignancy and her rash was managed with triamcinolone 0.1% topical ointment.This case adds to the literature on pembrolizumab-induced skin reactions, emphasizing the nuanced understanding needed for diagnosis and treatment, particularly in the context of a pre-existing dermatologic condition exacerbated by ICI therapy.

Pembrolizumab-Induced Epidermotropic CD8+ Dermatitis in a Patient with Multiple Squamous Cell Carcinomas

Dermatofibromas are benign cutaneous soft-tissue tumors characterized by solitary or multiple, firm red-brown to black dermal nodules found on the trunk or extremities. Dermatofibromas most frequently affect middle-aged adults and have a slight preponderance in females. Variants of dermatofibroma include hemosiderotic, aneurysmal, epithelioid and deep fibrous histiocytomas, cellular, lipidized, lichenoid, keloidal, atrophic, and atypical. 

Diagnosis of the classical type of dermatofibroma is made clinically and based on dermoscopic patterns; however, the clinical and histologic heterogeneity observed in dermatofibroma variants can pose a diagnostic challenge and may be difficult to distinguish from potentially aggressive malignancies. Notably, hemosiderotic dermatofibroma has been reported to clinically simulate melanoma, while atypical dermatofibroma, is often mistaken histologically for sarcoma. 

Herein, we report a unique presentation of a patient with a recurrent atypical melanocytic nevus and multiple benign dermatofibromas masquerading as potentially malignant counterparts.

Dermatological Deception: Massive Dermatofibroma and Atypical Melanocytic Nevus Mimicking Malignancy

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.

Inspection of Deep Tumor Margins in Mohs Micrographic Surgery for Accurate Cutaneous Squamous Cell Carcinoma Staging

Dermatology (Clinical Vignettes)

poster

Welcome to the **largest national, multi-specialty research** event featuring research from more than 750 medical students, residents, fellows, and international medical graduates.

Use the buttons below or navigation menu to access the event.
 

[![](https://assets.underline.io/markdown_image/1/image/20e1e77aa954efeac7a15d84c85eb383.jpg)](https://underline.io/events/468/sessions?searchGroup=all)
 
[![](https://assets.underline.io/markdown_image/1/image/068522d81aca0b68a369787c7dfccd1b.jpg)](https://underline.io/events/468/posters?searchGroup=all)
 
[![](https://assets.underline.io/markdown_image/1/image/d3971ece79d5e5575b178bdc2c8bbfae.jpg)](https://underline.io/events/468/help-desk)
 

#### Event Details

The 2024 American Medical Association Research Challenge includes a poster symposium hall and a semifinals hall with the top scored research. **Log in at any time throughout the event to:**

* **View posters and presentations** on a variety of topics and specialties
* **Score posters in the semifinals** to help decide the top five finalists (AMA member exclusive opportunity)
* **Connect with participants** and provide feedback to help advance their research

At the conclusion of this event, the AMA will announce the top five finalists who will advance to the AMA Research Challenge finals, present their research to an elite panel of judges, and compete to win a $10,000 grand prize presented by Laurel Road. 

### Grand Prize Sponsor

AMA would like to thank Laurel Road for sponsoring a $10,000 grand prize for the winner of the AMA Research Challenge. Laurel Road is not involved in winner selection process. The winner will be announced on February 20, 2025 during the AMA Research Challenge finals. Payment of the grand prize will be directly from Laurel Road. See the AMA Research Challenge Official Rules for terms and conditions.

[![](https://assets.underline.io/uploads/markdown_image/1/image/611e331d4a0eba0920f240cfc04b4d77.png)](https://www.laurelroad.com/)

You need to log in with the email address you registered with. Access credentials have been sent to your email. 

Please be sure to check your spam and other email folders if you do not see an email confirmation right away.

Please log in to explore this event.

**There is no registration fee for this event! **

If you have used the AMA Research Challenge platform previously, please click the ‘Log-in’ button below. If you do not remember your password, please click “forgot password” and follow prompts to reset your password. After resetting your password, please refresh your webpage to access the platform.

Register to explore research in a variety of topics. AMA members get exclusive access to score posters in the semifinals. 

**Please use this link [here](https://www.ama-assn.org/member-benefits/events/ama-research-challenge) to register for free.**

Registration Is Required

AMA Research Challenge 2024 

Join the AMA Research Challenge poster symposium and semifinals to explore top research posters and score posters in the semifinals (an AMA member exclusive opportunity).

 Dermatology

Welcome to the **largest national, multi-specialty research** event featuring research from nearly 700 medical students, residents, fellows, and international medical graduates.

Use the buttons below or navigation menu to access the event.
 


[![](https://assets.underline.io/uploads/markdown_image/1/image/3e33a8c754cc49610b30950617d813e7.png)](https://underline.io/events/434/sessions?searchGroup=all)
 
[![](https://assets.underline.io/uploads/markdown_image/1/image/551404d429c4e274f9a54cbdd7081918.png)](https://underline.io/events/434/posters?searchGroup=all)
 
[![](https://assets.underline.io/uploads/markdown_image/1/image/677d92f566b880cebd36905fc738fc10.png)](https://underline.io/events/434/lounge)
 
[![](https://assets.underline.io/uploads/markdown_image/1/image/c7392833c7261c3874c5b43fa2f4df19.png)](https://underline.io/events/434/help-desk)
 

#### Event Details

The 2023 American Medical Association Research Challenge includes a poster symposium hall and a semifinals hall with the top scored research. **Log in at any time throughout the event to:**

* **View posters and presentations** on a variety of topics and specialties
* **Score posters in the semifinals** to help decide the top five finalists (AMA member exclusive opportunity)
* **Connect with participants** and provide feedback to help advance their research
* **Attend education sessions** with physician experts on key research topics

At the conclusion of this event, the AMA will announce the top five finalists who will advance to the AMA Research Challenge finals, present their research to an elite panel of judges, and compete to win a $10,000 grand prize sponsored by Laurel Road. 

### Grand Prize Sponsor

AMA would like to thank Laurel Road for sponsoring a $10,000 grand prize for the winner of the AMA Research Challenge. Laurel Road is not involved in the judging or scoring process to select the winner. The winner will be announced on February 4, 2024 during the AMA Research Challenge finals. Payment of the grand prize will be directly from Laurel Road. See the AMA Research Challenge Official Rules for terms and conditions.

![](https://assets.underline.io/uploads/markdown_image/1/image/611e331d4a0eba0920f240cfc04b4d77.png)

**There is no registration fee for this event! **

Register to explore research in a variety of topics. AMA members get exclusive access to score posters in the semifinals.

**Please use this link [here](https://www.ama-assn.org/about/events/ama-research-challenge) to register for free.**

AMA Research Challenge 2023

Join the AMA Research Challenge poster symposium and semifinals to explore top research posters, score posters in the semifinals (an AMA member exclusive opportunity) and attend education sessions with experienced physicians to learn tips to advance your research and career. 

Clinical Vignettes | Dermatology

Welcome to the largest national, multi-specialty research event **featuring research from 750 medical students, residents and fellows, and international medical graduates.**


#### Event Details
The 2022 American Medical Association Research Challenge includes a poster symposium hall and a semifinals hall with the top scored research. Log in at any time throughout the event to:
* **View posters and presentations** on a variety of topics and specialties
* **Score posters in the semifinals** to help decide the top five finalists (AMA member exclusive opportunity)
* **Connect with participants** and provide feedback to help advance their research

At the conclusion of this event, the AMA will announce the top five finalists who will advance to the AMA Research Challenge finals, present their research to an elite panel of judges and compete to win a $10,000 grand prize sponsored by Laurel Road.
 

#### Attend Live Forums
**Oct. 20, 6 — 7 p.m. Central**
 **How to plan a career in academic medicine** 
 Learn how to plan a career in academic medicine and get your questions answered. [Access Here](https://underline.io/events/363/lounge)
 
 **Speakers**
![](https://assets.underline.io/uploads/markdown_image/1/image/d5adb133dfc58eb0a6d469e9cedcd5d4.jpg)
Ricardo Correa, MD, EdD
![](https://assets.underline.io/uploads/markdown_image/1/image/5f9437ab87861538bf02b9ca7c0d926e.jpg)
Stuart M. Greenstein, MD
![](https://assets.underline.io/uploads/markdown_image/1/image/05b1b637c99286d558c371f8e8b185ce.jpg)
Stephanie Strohbeen, MD
 
 **Oct. 22, 11 a.m. — Noon Central**
 **How to get published**
 Learn tips to get your research published and get your questions answered. [Access Here](https://underline.io/events/363/lounge)
 
 **Speakers**
![](https://assets.underline.io/uploads/markdown_image/1/image/8ce6235e957d31cb5e6f9097cc6f6972.jpg)
Jessica Li, MD/PhD Candidate
![](https://assets.underline.io/uploads/markdown_image/1/image/9950ef2e0237f54cb3d8280334d42491.jpg)
Charles Lopresto, DO

### Sponsor
AMA would like to thank Laurel Road for sponsoring a $10,000 grand prize for the winner of the AMA Research Challenge. Laurel Road is not involved in the judging or scoring process to select the winner. The winner will be announced on Dec. 7 during the AMA Research Challenge finals. Payment of the grand prize will be directly from Laurel Road. See the AMA Research Challenge Official Rules for terms and conditions.

![](https://assets.underline.io/uploads/markdown_image/1/image/611e331d4a0eba0920f240cfc04b4d77.png)

**There is no registration fee for this event! **

Register to explore research in a variety of topics. AMA members get exclusive access to score posters in the semifinals.

**Please use the link below to register for free if you have not already done so:**

https://www.ama-assn.org/about/events/ama-research-challenge

AMA Research Challenge 2022

Welcome to the largest national, multi-specialty research event featuring research from 750 medical students, residents and fellows, and international medical graduates.


Jeffrey Chen

3

SHORT BIO

Presentations

Pembrolizumab-Induced Epidermotropic CD8+ Dermatitis in a Patient with Multiple Squamous Cell Carcinomas

Dermatological Deception: Massive Dermatofibroma and Atypical Melanocytic Nevus Mimicking Malignancy

Inspection of Deep Tumor Margins in Mohs Micrographic Surgery for Accurate Cutaneous Squamous Cell Carcinoma Staging

Stay up to date with the latest Underline news!

PRESENTATIONS

CONFERENCES

COMPANY

RESOURCES