Home >> ALL ISSUES >> 2016 Issues >> Non-melanocytic lesions—preventing pitfalls in diagnosis

Non-melanocytic lesions—preventing pitfalls in diagnosis

image_pdfCreate PDF

Karen Lusky

February 2016—Musician Lauryn Hill has been quoted as saying, “Reality is easy. It’s deception that’s the hard work.” That viewpoint just might resonate with pathologists who sometimes have to diagnose deceiving-looking skin lesions.

In a talk at CAP ’15, Deborah L. Cook, MD, professor of pathology and director of dermatopathology at the University of Vermont, shared several case examples that illustrate that investigative effort. All of them involve non-melanocytic malignancies known to mimic benign entities and the converse—“the proverbial wolf in sheep’s clothing” and “sheep in wolf’s clothing,” as she puts it.

In one case, a woman in her 50s developed a firm, mildly tender nodule on her flank. The clinician thought the nodule was a cyst or dermatofibroma. At low magnification, it did look like a dermatofibroma, particularly because the clinician had suggested a diagnosis of dermatofibroma, Dr. Cook says. The growth pattern showed “small cells percolating through the dermis of the skin.” At higher magnification, however, the pattern was fairly typical of lobular breast cancer.

Dermato1Immunohistochemistry testing helped confirm the diagnosis. “CK7 [cytokeratin 7] was positive. It isn’t specific for breast cancer but it is for epithelial cells. A dermatofibroma would not stain with CK7,” she says. “This showed it was at least epithelial and then there was the pattern, and we did do additional studies that at least suggested breast cancer.”

They also subsequently found out that the patient had a history of breast cancer. “The use of electronic health records allows us to more easily access our patients’ previous history that we have here so we had that information,” she says.

Dr. Cook notes that it’s not that common for a skin metastasis to be the first sign of breast cancer. What’s probably more common, she adds, is to initially diagnose an internal malignancy, such as renal cell carcinoma, in a skin metastasis, which usually presents as a firm nodule. “Renal cell carcinoma can sometimes be clinically silent in the kidney itself but metastasize, often to the skin.”

In another case, a male in his early 20s had a small, slowly growing, asymptomatic pink nodule on his dorsal wrist. At low to medium magnification, the nodule looked similar to granuloma annulare, Dr. Cook says. In this common and benign inflammatory process, the cells consist of macrophages or histiocytes and have a rather palisaded appearance, she explains. When viewed at a higher magnification, however, the cells no longer resembled histiocytes. “They looked more atypical.”

“What really cinched it,” she says, is IHC testing that showed cytokeratin positivity. “The histiocytes in granuloma annulare would be CD68 or CD163 positive and cytokeratin negative.”
The diagnosis? Epithelioid sarcoma, which Dr. Cook notes also has a palisaded appearance under the microscope. The malignancy is aggressive, she says, but “early detection does help.”

An epithelioid sarcoma isn’t a distinctive lesion clinically, Dr. Cook cautions. There were two clues: the patient’s age, as the cancer affects young adults, and the tumor’s location on a distal extremity where it typically occurs.

Another case involved what was likely a long-standing cancer. A middle-aged man sought evaluation for a 20 × 15 cm violaceous, fixed, firm growth that had been on his back for several years. It was enlarging and becoming more painful. A limited needle core biopsy was reported as “CD34-positive, spindle cell proliferation, favor solitary fibrous tumor; no features of malignancy seen.” The man had the mass removed when an MRI showed that it was large and growing.

Dermato2Dr. Cook says she and colleagues had a broad differential that included neurofibroma owing to its myxoid background and bland spindle cell morphology. So they used an S-100 protein immunostain, which helps distinguish “tumors of neural crest origin, such as peripheral nerve sheath tumor and melanoma,” she says. The S-100 protein was used “more to rule out a nerve sheath neurofibroma, which isn’t a malignancy.” S-100 protein was negative.

CD34 was positive, however, which would be expected to be seen in a dermatofibrosarcoma protuberans (DFSP), which is malignant, Dr. Cook says. “[CD34] marks progenitor cells but it’s also positive in a variety of lesions so you really have to interpret it with morphology. It is also positive in stem cells in the bone marrow and normal cells too.”

Dr. Cook says there was another key to cracking the case: Although the patient had the myxoid variant of DFSP, which is unusual, they found focal areas in the tumor that were more classic for the cancer. In addition, cytogenetic testing showed the tumor had an abnormal karyotype that is seen in DFSP.

Why didn’t the needle core biopsy pick up indications of malignancy? “Unfortunately, this particular malignancy is made up of very bland cells,” Dr. Cook says. “So if you just look at the cells in a limited specimen or in cytology needle aspirate, it will appear very bland and won’t have typical features of malignancy. But then when you look at a tissue section and see the growth pattern and other features, it’s malignant.”

Dr. Cook makes it clear that she’s not criticizing the decision to start with the needle core biopsy. The case in question included numerous entities in the differential diagnosis, she says, “and needle core biopsy is an excellent first diagnostic tool to try to eliminate [those] and direct further investigational pathways.”

Dr. Cook also discussed two patients who had benign lesions that have the potential to become malignant or may be interspersed with cancerous lesions.

For the first case, Dr. Cook showed a picture of a rather angry-looking, well-circumscribed verrucous keratotic plaque on the shin of a woman in her 60s. The patient said the plaque had been present for several months. The differential diagnosis included squamous cell carcinoma.

CAP TODAY
X