Rossitza Lazova

Background: The most salient histopathological features of psoriasis are epidermal hyperplasia, hypogranulosis, parakeratosis, dilated capillaries in dermal papillae, and intraepidermal and intracorneal neutrophils. Several additional “nonclassic” features of psoriasis have recently been reported, including necrotic keratinocytes (NK). To determine the diagnostic utility of NK, we characterized NK in a large cohort of psoriasis cases compared with psoriasiform spongiotic dermatitis (PSD) and normal skin.Methods: NK were quantified in 101 cases of psoriasis, 20 cases of PSD, and 20 cases of normal skin. The location of NK within the lower, middle, or upper thirds of the epidermis was recorded.Results: NK were identified in 77/101 (76%) of psoriasis cases. By comparison, NK were seen in 8/20 (40%) cases of PSD and 4/20 (20%) cases of normal skin. The linear concentration of NK was significantly higher in psoriasis (0.36 NK/mm) compared with PSD (0.12 NK/mm) and normal skin (0.03 NK/mm) (P= 0.0009). NK were preferentially located in the upper (58%) and middle (31%) epidermis in psoriasis.Conclusions: NK are a common feature of psoriasis and have a predilection to the upper layers of epidermis. Superficial NK may provide additional diagnostic support for psoriasis in challenging or borderline cases.

Purpose: Distinguishing benign nevi from malignant melanoma using current histopathological criteria may be very challenging and is one the most difficult areas in dermatopathology. The goal of this study was to identify proteomic differences, which would more reliably differentiate between benign and malignant melanocytic lesions.Methods: We performed histolpathology ‐ guided mass spectrometry (HGMS) profiling analysis on formalin‐fixed, paraffin embedded tissue samples to identify differences at the proteomic level between different types of benign nevi and melanomas. A total of 756 cases, of which 357 cases of melanoma and 399 benign nevi, were included in the study. The specimens originated from both biopsies (376 samples) and tissue microarray (TMA) cores (380 samples). After obtaining mass spectra from each sample, classification models were built using a training set of biopsy specimens from 111 nevi and 100 melanomas. The classification algorithm developed on the training data set was validated on an independent set of 288 nevi and 257 melanomas from both biopsies and TMA cores.Results: In the melanoma cohort, 239/257 (93%) cases classified correctly in the validation set, 3/257 (1.2%) classified incorrectly, and 15/257 (5.8%) classified as indeterminate. In the cohort of nevi, 282/288 (98%) cases classified correctly, 1/288 (0.3%) classified incorrectly, and 5/288 (1.7%) were indeterminate. HGMS showed a sensitivity of 98.76% and specificity of 99.65% in determining benign vs malignant.Conclusion: HGMS proteomic analysis is an objective and reliable test with minimal tissue requirements, which can be a helpful ancillary test in the diagnosis of challenging melanocytic lesions.

A 37‐year‐old pregnant woman presented with a 2‐cm irregular reddish nodule on her left upper arm during pregnancy. A biopsy from the lesion showed a 2.2‐mm thick malignant melanoma with intravascular invasion, 25 mitosis/mm² and no ulceration. Following induction of labor, the patient underwent re‐excision with sentinel lymph node biopsy. This showed no residual melanoma and no lymph node metastasis. The newborn boy had multiple pigmented lesions on the trunk, some of which were large and irregular. Two were biopsied and histologic examination showed dense dermal proliferation of medium sized melanocytes with multiple mitotic figures and no maturation with their descent into the dermis, raising suspicion of transplacental metastases. Examination of the placenta failed to show metastatic lesions. Multiplex polymerase chain reaction (PCR)‐based genotyping, including testing for amelogenin locus for sex chromosome determination, demonstrated the presence of Y chromosome material in the melanocytes of the newborn's lesions excluding maternal origin. A diagnosis of congenital nevi was rendered. Subsequently, Imaging Mass Spectrometric analysis of the mother's lesion showed proteomic signature expression indicative of malignant melanoma, whereas the two lesions in the newborn showed changes indicative of nevi. This case demonstrates the utility of genotyping and Mass Spectrometry analysis in this challenging clinical scenario

Subcutaneous histiocytoid Sweet's syndrome is a rare variant of histiocytoid Sweet's syndrome (SS). We present a 68‐year‐old woman with subcutaneous histiocytoid SS in association with refractory myelodysplastic syndrome transformed to acute myeloblastic leukemia (AML), status post induction chemotherapy and with persistent blasts (50%) in the bone marrow and blood, accompanied with neutropenia. The patient presented to the emergency room with fever and altered mental status. Clinical examination revealed approximately 20 scattered 0.5–2 cm, pink to pink‐purple non‐tender firm nodules on the legs and left arm. The differential diagnosis included Sweet's syndrome (deep), leukemia cutis, infection, polyarteritis nodosa and erythema nodosum. Histopathologic examination of a biopsy from the left arm revealed a nodular infiltrate of neutrophils and histiocytoid mononuclear cells solely in the lobular compartment of the subcutaneous fat with focal areas of necrosis. Most cells in the infiltrate labeled with myeloperoxidase (MPO) including the histiocytoid cells. The cells were negative for CD34 and CD117. All special stains for microorganisms were negative. A diagnosis of subcutaneous histiocytoid SS was made. A subcutaneous histiocytoid SS should be suspected when a neutrophilic/histiocytoid panniculitis, occurring in the setting of myeloid disorders, is encountered and after exclusion of an infectious process and leukemia cutis.

Background: Spitz nevi and Spitzoid melanomas show overlapping histopathologic features, often making the diagnosis challenging. The p16 protein functions as a tumor suppressor and loss of its expression may be seen in some melanomas.Methods: We evaluated 18 Spitz nevi and 19 Spitzoid melanomas from the Yale Spitzoid Neoplasm Repository for p16 expression. A staining intensity score (SIS) was calculated by multiplying a score for the percentage of stained cells (0–3) by a score for staining intensity (0–3).Results: Staining with p16 was positive in 15/18 (83%) Spitz nevi and 15/19 (79%) Spitzoid melanomas (p = 0.73). Both Spitz nevi and Spitzoid melanomas had a similar SISs, 4.9 and 3.8, respectively (p = 0.057). All 19 patients with Spitzoid melanomas had poor outcome with either death (6 patients) or metastases (13 patients) at a median (3 years) and mean (5.4 years) follow up. In contrast, all 18 patients with Spitz nevi had a benign course with no adverse events at a median (4 years) and mean (4 years) follow up.Conclusions: We found no significant difference in p16 staining in Spitz nevi and Spitzoid melanomas. We conclude that p16 does not appear to be a useful immunohistochemical marker in distinguishing between Spitz nevi and Spitzoid melanomas.

P75 nerve growth factor receptor (p75 NGF-R) is a low-affinity receptor expressed on the surface of neural crest–derived cells and in a variety of neural tumors. Strong p75 NGF-R expression has been found in spindle cell melanoma (SCM). We studied spindle cell neoplasms of sun-damaged skin to determine whether this marker can reliably distinguish between SCM and other spindle cell malignancies. We evaluated the staining of p75 NGF-R, S100, and HMB-45 in 11 cases of SCM, 16 cases of spindle cell squamous cell carcinoma (SCSCC), 19 cases of spindle cell atypical fibroxanthoma, 6 cases of cutaneous leiomyosarcoma, and 20 scars. Staining with p75 NGF-R was positive in all 11 of 11 (100%) cases of SCM, whereas S100 stained 10 of 11 (91%) cases, and HMB-45 was negative in all SCMs. In addition, there was superior intensity of the staining for p75 NGF-R in comparison to S100. P75-NGF-R showed focal positivity in 3 of 16 (19%) cases of SCSCC. None of the rest of the cases of SCSCC, and none of the cases of spindle cell atypical fibroxanthoma, cutaneous leiomyosarcoma, and scars expressed p75 NGF-R, S100, or HMB-45. P75 NGF-R is a useful marker to distinguish SCM from other spindle cell neoplasms of sun-damaged skin. This marker exhibits greater sensitivity than S100 in identifying SCM and may be a useful diagnostic and ancillary stain especially in the setting of an S100 negative spindle cell neoplasm.