Abstract:

This video features a comprehensive lecture by Dr. Jerad Gardner on practical challenges in dermatopathology and soft tissue pathology. The presentation focuses on differentiating benign lesions from their malignant mimics, as well as introducing several new and evolving entities defined by molecular genetics.

Key topics include adnexal tumors that mimic carcinoma, such as desmoplastic trichilemmoma and trichoepithelioma, and their distinction from microcystic adnexal carcinoma using architectural clues and immunohistochemistry (CK20). The lecture covers keratinocytic lesions like verrucous carcinoma and its benign mimic, verruciform xanthoma. A significant portion is dedicated to complex melanocytic neoplasms, including desmoplastic melanoma, BAP1-inactivated nevi/melanocytomas, and rare tumors with specific gene fusions (CRTC1-TRIM11, EWS-R1). The discussion also explores a variety of rare spindle cell tumors, emphasizing the importance of recognizing entities with paradoxical features, such as the dramatic pleomorphism but low mitotic activity seen in superficial CD34+ fibroblastic tumors. Throughout the lecture, Dr. Gardner emphasizes the importance of low-power architectural assessment, key immunohistochemical markers, clinical correlation, and the growing role of molecular diagnostics in providing accurate diagnoses and guiding patient management.

A Practical Guide to Difficult Skin and Soft Tissue Tumors

• 0:05:06 Distinguishing Benign from Malignant: Desmoplastic Trichilemmoma This benign hair follicle tumor can mimic infiltrative carcinoma (BCC or SCC) in its ulcerated center. The key to diagnosis is recognizing the well-circumscribed, smooth borders and benign basaloid nests at the periphery of the lesion, a feature described as "pseudo-infiltration." Correctly identifying it prevents unnecessary aggressive surgery.

• 0:23:55 The Sclerosing Basaloid Tumor Differential A case of desmoplastic trichoepithelioma is used to illustrate the differential diagnosis for tumors with infiltrating cords in dense collagen. This includes syringoma, morpheaform BCC, and microcystic adnexal carcinoma (MAC).

  • Key takeaway: Cytokeratin 20 (CK20) is a crucial stain, as it highlights scattered benign Merkel cells in trichoepithelioma, which are absent in BCC and MAC.

• 0:40:40 Identifying Microcystic Adnexal Carcinoma (MAC) Unlike its benign mimics, MAC is defined by its aggressive local behavior. While the cells are cytologically bland, the key diagnostic features are deep infiltration into fat and skeletal muscle, and prominent perineural/intraneural invasion.

• 0:52:59 A Dangerous Acral Lesion: Digital Papillary Adenocarcinoma This rare sweat gland tumor occurs on the digits and is characterized by a mix of cystic, papillary, and solid patterns. It is often cytologically bland but has significant metastatic potential (up to 25%). It is critical to distinguish it from benign hydradenomas to ensure proper treatment, which involves excision with negative margins.

• 1:09:51 An In-Situ Precursor: Endocrine Mucin-Producing Sweat Gland Carcinoma This lesion, often found on the eyelid, presents as a cystic tumor with a cellular component that is positive for neuroendocrine markers (e.g., INSM1). It is an in-situ precursor to invasive mucinous carcinoma.

  • Key takeaway: Identifying this in-situ component alongside an invasive mucinous carcinoma is definitive proof of a primary skin tumor, ruling out a metastasis from another site like the breast.

• 1:29:13 Mimics on the Foot: Verrucous Carcinoma This is a very well-differentiated, low-grade squamous cell carcinoma characterized by long, bulbous rete ridges pushing deep into the dermis. Cytology is bland, making deep invasion the primary diagnostic feature. It has a high local recurrence rate, and margins can be deceptively difficult to assess.

• 1:47:41 A Benign Mimic: Verruciform Xanthoma Often found in the anogenital or oral regions, this benign lesion has a warty surface with bright pink parakeratosis, superficially mimicking verrucous carcinoma. The definitive diagnostic feature is the presence of foamy, lipid-laden histiocytes (xanthoma cells) filling the dermal papillae.

• 1:59:10 An Important Incidental Finding: Underlying CLL/SLL In a case of aggressive squamous cell carcinoma, a background infiltrate of chronic lymphocytic leukemia (CLL) was discovered. This underlying, previously undiagnosed CLL explained the patient's immunosuppressed state and the cancer's aggressive behavior. Pathologists should be aware of this association.

• 2:14:11 The Spectrum of Desmoplastic Melanoma This melanoma subtype can be deceptively bland, mimicking scar tissue or neurofibroma. Key clues include its presence in sun-damaged skin of older adults, lymphocytic aggregates, and perineural invasion. Purely desmoplastic forms have a lower metastatic risk than conventional melanoma, but prognosis worsens when a more cellular spindle cell component is present.

• 3:03:04 BAP1-Inactivated Nevus ("Bapoma") These lesions feature a conventional nevus with a distinct nodule of larger, atypical epithelioid cells. The defining feature is the loss of nuclear BAP1 staining in the atypical nodule. This can be sporadic or a marker for a germline BAP1 syndrome, which predisposes to uveal melanoma and mesothelioma. Genetic counseling is recommended.

• 3:26:15 A Benign Tumor Mimicking Liposarcoma Atypical pleomorphic lipomatous tumor represents the high-end of the spectrum for pleomorphic lipoma. It can be large and have significant atypia, mimicking well-differentiated liposarcoma. The key distinction is that it is MDM2-negative and shows RB1 loss, confirming its benign nature.

• 3:51:31 A Paradoxical Tumor: Superficial CD34+ Fibroblastic Tumor This rare, low-grade tumor is characterized by dramatic, bizarre pleomorphism but a paradoxically very low or absent mitotic rate. It is diffusely CD34 positive and can show focal keratin expression. It's crucial to distinguish it from high-grade pleomorphic sarcoma due to its much better prognosis.

• 4:07:53 An Emerging Entity: NTRK-rearranged Spindle Cell Neoplasm This is a group of tumors defined by an NTRK gene fusion. They have highly variable morphology but often co-express CD34 and S100. Their behavior exists on a spectrum from benign to fully malignant sarcoma. Recognition is important due to the availability of targeted TRK inhibitor therapies for malignant cases.