Patrick O. Emanuel

Defining diabetic dermopathy.

Diabetic dermopathy presents as well‐demarcated, hyperpigmented, atrophic depressions, macules or papules located on the anterior surface of the lower legs of diabetic patients. The histopathology remains poorly defined which may in part be due to the fact that the lesions are rarely biopsied. An advantage of studying autopsy material is the ease of obtaining large biopsy specimens. To further define the histopathological features of this entity, we studied tissue taken from characteristic lesions at autopsy. Inclusion criteria included the presence of the lesions and diabetes‐related nephroarteriolosclerosis at autopsy. Surprisingly, only four out of 14 skin biopsies showed moderate to severe wall thickening of arterioles or medium‐sized arteries on periodic acid Schiff (PAS) stains. Only mild basement membrane thickening was noted in 11 of 14 which was highlighted by the PAS stain. Pigmented material was identified within the dermis of 13 cases. In 10 of the cases, the material was positive for Perl’s iron stain. Ten cases had material staining positive for Fontana–Masson in the dermis. Nine cases had markedly increased epidermal melanin. The findings suggest that hemosiderin deposition in conjunction with the deposition of melanin contribute to the clinical features of diabetic dermopathy.

Aggressive osteogenic desmoplastic melanoma: a case report

A case of an osteogenic desmoplastic melanoma occurring on the sole of the foot of a 60‐year‐old African American man is described. The tumor measured 4.8 cm in greatest dimension, invaded to a thickness of 2.2 cm and metastasized to four of ten inguinal lymph nodes. The majority of the tumor had a classic desmoplastic phenotype with malignant spindle cells set in a sclerotic and myxoid matrix and foci of lymphocyte aggregation. In other areas, there were thick trabeculae of bone rimmed by malignant epithelioid melanocytes. There was a markedly atypical lentiginous hyperplasia in the overlying epidermis. Imaging showed no continuity with the underlying calcaneus. The tumor was characterized immunohistochemically by S100 positivity. Pathologists should be aware of this diagnosis and should differentiate it from osteosarcoma.

Poorly differentiated squamous cell carcinoma with osteoclastic giant-cell-like proliferation.

Although osteoclast giant‐cell‐like proliferations have been reported in a diverse range of human malignancies, to the best of our knowledge, they have never been described in cutaneous squamous cell carcinoma (SCC). Histologically, osteoclastic giant cell tumors within extraosseous malignancy resemble their bony and soft tissue counterparts, with round to spindle‐shaped cells admixed with osteoclast‐like multinucleate cells. These cells should be distinguished from sarcomatoid differentiation within a carcinoma; they have a benign morphology with a low nuclear to cytoplasmic ratio, minimal pleomorphism/mitoses and negative immunohistochemistry for cytokeratin. The authors report the rare occurrence of osteoclast‐like giant cells (OGCs) and accompanying epithelioid histiocytes lacking overtly malignant features in association with a poorly differentiated SCC occurring on sun‐damaged skin. Immunohistochemically, the area rich in OGCs was strongly positive for CD68 and completely negative for cytokeratin, whereas the poorly differentiated infiltrative area had the reverse immunophenotype and nuclear positivity for p63. The histological differential diagnosis and the origin of the proliferation are discussed in this article.

Cervical parakeratosis/hyperkeratosis as an important cause for false negative results of Pap smear and human papillomavirus test

Like any screening method, Pap and HPV tests are subject to false negative results.

‘Pseudo‐Mikulicz’ cells

To the Editor, Soon after von Hebra’s initial description of rhinoscleroma in 1870, Mikulicz-Radecki described the typical foamy cells (Mikulicz cells) which bear his name as a component of that disorder.1 Mikulicz also described Mikulicz’s disease, which represents a Sjogren’s syndrome-like disorder with chronic dacryoadenitis and bilateral parotid and lacrimal gland enlargement.2 Rhinoscleroma was first documented in pre-Columbian Mayan civilizations. More recently, it has been reported in poorer regions of Central Africa, Eastern and Central Europe, the Middle East, India and Indonesia. There are also cases in non-endemic areas that are explainable by increased migration.3– 5 Classic histopathological findings in early rhinoscleroma (before the onset of sclerosis) include Mikulicz cells, numerous plasma cells and Russell bodies (Fig. 1A,B). The Mikulicz cells are typically laden with the causative organisms, either Klebsiella pneumoniae subspecies rhinoscleromatis or K. pneumoniae subspecies ozaenae. The microbes may be showed with periodic acid-Schiff, silver stains or even immunohistochemical stains. The Mikulicz cell has been identified as a macrophage and is typically 100–200 μm in diameter. The vacuoles observed in Mikulicz cells via electron microscopy are considered to be phagosomes containing bacterial mucopolysaccharide, bacteria and swollen mitochondria. It has been postulated that this bacterial mucopolysaccharide is non-digestible and resides in the phagosomes of tissue macrophages, increases osmotic pressure and forms vacuoles that rupture not only the phagosomes but also the colonized cells.6 There is a possibility that impaired cellular immunity may play a role in the pathogenesis of rhinoscleroma. The CD4/CD8 cell ratio in lesional tissue may be reduced, and this change possibly reflects a diminished T-cell response.7 The case we encountered bore a striking resemblance to rhinoscleroma (Fig. 1C, D). There were many plasma cells and Russell bodies accompanied by pale macrophages morphologically identical to Mikulicz cells. We term these macrophages pseudoMikulicz cells. This specimen was obtained from an 88-year-old patient with an 8 mm solitary hyperkeratotic lesion on the temple. Histopathologically, there was a small focus of squamous cell carcinoma flanked by superficial pustular folliculitis (focal folliculitis is marked with an arrow in Fig. 1D). The patient has resided in urban New Zealand his entire life and had no history of recent travel. Special stains (Gram, periodic acid-Schiff and Ziehl-Neelsen) failed to reveal organisms. Immunohistochemistry with anti-CD4 and anti-CD8 failed to reveal an abnormal ratio. Clinical follow up revealed no evidence

Squamous cell carcinoma with enteric adenocarcinomatous differentiation

We report a highly unusual case of a primary cutaneous squamous cell carcinoma (SCC) with intermixed enteric‐type adenocarcinomatous dedifferentiation and a small component of undifferentiated mesenchymal differentiation. We believe this is the first time this form of phenotypic plasticity has been described in cutaneous SCC.

Unusual manifestation of histiocyte-rich peripheral T-cell lymphoma

To the Editor, When a dermatopathologist encounters a superficial and deep lymphohistiocytic infiltrate, a lengthy differential diagnostic list is elicited. When neurotopism is noticed, and the requisition form claims the patient has localized paresthesia, infection by mycobacterium leprae warrants particular consideration. We read with interest the paper by Summers et al. published early online in the Journal.1 We encountered a similar case 3 years ago, which we found particularly challenging. The patient was a 65-year-old female who presented with weight loss, malaise and sensory deficits. A neurological examination confirmed multiple foci of paresthesia and a peripheral neuropathy. There was no discernable adenopathy. As part of the initial workup for the neurological deficits apparent on clinical exam, an infiltrate confined to the dermis was unwittingly biopsied by the surgeon performing a deltoid skeletal muscle biopsy. Both the surgeon and neurologist denied any clinical evidence of a cutaneous lesion, and unfortunately we did not have an opportunity to clinically examine the patient at initial presentation. Histopathologically, the infiltrate was superficial and deep, nodular, and rather dense at scanning magnification (Fig. 1). Higher power revealed an abundance of histiocytes, occasionally forming loose granulomas and an accompanying population of small lymphocytes, which, on careful examination displayed irregular nuclear contours (Fig. 2), and rare mitosis. Of note – and peculiar to this case – was that the infiltrate involved and appeared to track down multiple small dermal nerves (Fig. 3). Interestingly, the muscle specimen (which accompanied this generous skin biopsy), though free of the infiltrate, displayed evidence of acute partial denervation and type-2 myofiber atrophy. Fite stain, acid-fast bacillus stain and anti-spirochete immunohistochemistry were negative. The lymphocytes were positive for CD3 (Fig. 4), CD43 and CD5, and negative for CD79a, L26 and CD30. CD68 was strongly expressed by the histiocytes (Fig. 5). The histiocytes failed to express B-cell markers. Subsequent workup revealed involvement of the kidney and spleen; this was discovered radiologically and an infiltrate identical to that identified in the dermis was demonstrated with subsequent biopsy. Notably, the atypical T-cell infiltrate was accompanied by the histiocytic population in all organs biopsied. T-cell receptor rearrangement studies were performed but failed to reveal a rearrangement in the biopsy from the skin and from the spleen [polymerase chain reaction (PCR) for V and J regions]. The studies were not performed on the liver biopsy. Peripheral blood flow cytometry revealed an increased CD4 : CD8 ratio, but failed to reveal an atypical population. Given the morphology and immunohistochemical profile, the findings were interpreted as systemic peripheral T-cell lymphoma, unspecified, with rich histiocyte content (Lennert’s lymphoma). It should be noted that the presence of granulomas in a T cell lymphoma of the skin is no reason to classify the lymphoma as Lennert’s lymphoma; the histiocytes in this case were accompanying the atypical infiltrate in multiple organs which – in our view at least – confirmed the diagnosis. This case was unusual in that it was diagnosed by skin biopsy, showed histologic neurotropism and was associated with neurologic symptomatology. The patient remains without evidence of disease 38 months following diagnosis and treatment with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and the neurological deficits have apparently resolved.