We review the morphofunctional characteristics of CD34+ stromal fibroblastic/fibrocytic cells (CD34+ SFCs) and report our observations. We consider the following aspects of CD34+ SFCs: A) The confusing terms applied to this cell type, often combining the prefix CD34 with numerous names, including fibroblasts, fibrocytes, dendrocytes, keratocytes, telocytes and stromal, dendritic, adventitial, supraadventitial, perivascular, paravascular and delimiting cells; B) Changes in their immunophenotype, e.g., loss of CD34 expression and gain of other markers, such as those defining mesenchymal and derivate cells (myofibroblasts, osteoblasts, chondroblasts, adipocytes); C) Morphology (elongated or triangular cell body and thin, moniliform, bipolar or multipolar cytoplasmic processes), immunohistochemistry (co-expression of and changes in molecular expression) and structure (characteristics of nucleus and cytoplasmic organelles, and points of contact and junctions in quiescent and activated stages by light and electron microscopy); D) Location and distribution in the vessels (adventitia or external layer), in the tissues (connective, adipose, blood, muscle and nervous) and in the organs and systems (skin, oral cavity and oropharynx, respiratory, digestive, urinary, male, female, endocrine and lymphoid systems, serosal and synovial membranes, heart, eye and meninges); E) Origin from the mesoderm and cranial neural crest in the embryo, and from stem cells (themselves or other cells) and/or peripheral blood pluripotent stem cells (circulating progenitor cells) in post-natal life; F) Functions, such as synthesis of different molecules, progenitor of mesenchymal cells, immunomodulation, parenchymal regulation (growth, maturation and differentiation of adjacent cells), induction of angiogenesis, scaffolding support of other cells and phagocytic properties. Since CD34+ SFCs are the main reservoir of tissue mesenchymal cells (great mesenchymal potential, probably higher than that proposed for pericytes and other stromal cells), we dedicate a broad section to explain their in vivo behaviour during proliferation and differentiation in different physiologic and pathologic conditions, in addition to their characteristics in the human tissues of origin (adult stem cell niches); G) Involvement in pathological processes, e.g., repair (regeneration and repair through granulation tissue), fibrosis, tumour stroma formation and possible CD34+ SFC-derived tumours (e.g., solitary fibrous tumour, dermatofibrosarcoma protuberans, giant cell fibroblastoma, nuchal-type fibroma, mammary and extramammary myofibroblastoma, spindle and pleomorphic cell lipoma, and elastofibroma) and H) Clinical and therapeutic implications.

https://digitum.um.es/digitum/bitstream/10201/71974/1/Diaz-Flores-29-831-870-2014_compressed.pdf

CD34+ stromal cells/fibroblasts/fibrocytes/telocytes as a tissue reserve and a principal source of mesenchymal cells. Location, morphology, function and role in pathology.

Background The diagnosis of dermatofibrosarcoma protuberans (DFSP) in childhood is often difficult because of the deceptive appearance of the lesions. Little is known about congenital DFSP, the frequency of which is probably underestimated because the initial lesion may pass unnoticed. Observations We studied 9 DFSP congenital cases (8 plaques and 1 nodule) initially suspected to be benign lesions. The first biopsies or excisions were performed after a delay of 5½ months to 15 years. All cases were CD34+. Histologic patterns were similar to the DFSP adult classic pattern in 4 cases. One case was a Bednar tumor. The histologic diagnosis of the 4 remaining cases was difficult. The collagen, type I, α 1–platelet-derived growth factor β fusion gene (COL1A1-PDGFB) was detected by means of reverse transcriptase–polymerase chain reaction or fluorescence in situ hybridization. Conclusions All cases of congenital DFSP were difficult to identify clinically. The diagnosis was suspected by means of histologic and immunohistochemical evaluation and was confirmed using molecular analyses. This study illustrates the difficulties and pitfalls of the recognition of congenital DFSP and emphasizes the value of immunohistochemical study with anti-CD34 and complementary molecular analysis for all cutaneous spindle cell tumors and plaques in neonates and infants.

https://jamanetwork.com/journals/jamadermatology/articlepdf/411032/dob60035_203_210.pdf

A clinical, histologic, and molecular study of 9 cases of congenital dermatofibrosarcoma protuberans.

Over the past few years, a growing number of cutaneous tumors expressing CD34 is being reported. The list contains benign and malignant neoplasms as well as reactive and hamartomatous lesions of diverse lineages of differentiation, including fibroblastic, myofibroblastic, fibrohistiocytic, vascular, neural, adipocytic, smooth muscle, hematopoietic, melanocytic and epithelial. The more frequent diagnostic difficulties are found in spindle cell proliferations, mainly in those of the fibrocytic lineage. In part, this is because of the fact that in this area are, aside to well-defined entities, histologically and clinically diverse, recently reported cutaneous CD34-reactive lesions, whose definitions, limits and relationships are not completely established. The CD34 expression plays a key role in the differential diagnosis of some tumors, such as dermatofibrosarcoma protuberans, epithelioid sarcoma (ES) or pleomorphic hyalinizing angiectatic tumor of soft parts, with important therapeutic consequences. In others, as in desmoplastic trichilemmoma, it can help to resolve diagnostic problems in concrete cases. Finally, in many of the CD34-positive lesions, the diagnosis with the hematoxylin and eosin stain is straightforward. However, in all of them, the knowledge of the immunohistochemical profile contributes to our understanding of the cutaneous pathology.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-0560.2008.01212.x

CD34‐reactive tumors of the skin. An updated review of an ever‐growing list of lesions

Medallion-like dermal dendrocyte hamartoma (DH) and superficial (plaque-like) dermatofibrosarcoma protuberans (DFSP) are CD34-positive dermal neoplasms with overlapping clinicopathologic features. We analyzed the clinical, histomorphologic, and molecular criteria of 5 DH and 7 DFSP to delineate diagnostically relevant differences between incipient dermal DFSP and its benign look-alike, DH. We expand the clinical and histologic spectrum of DH. As medallion-like dermal DH is neither of dermal dendrocyte lineage nor a genuine hamartoma, we propose instead the descriptive term of plaque-like CD34-positive dermal fibroma (PDF). Both PDF/DH and DFSP presented as slightly pigmented and indurated plaques on neck, trunk, and extremities. Histologically, DFSP was characterized either by horizontally oriented spindle cell fascicles or by diffusely arranged fibroblasts within a slightly myxoid stroma in the upper two-thirds of the dermis, whereas PDF/DH presented with a cellular band-like fibroblastic proliferation mostly in the papillary and adjacent upper reticular dermis. Only one congenital PDF/DH in a 9-year-old boy extended into the septa of the subcutaneous fat. Formalin-fixed paraffin-embedded archival tissue was used for detection of the COL1A1-PDGFB gene rearrangement by multiplex reverse transcription-polymerase chain reaction (RT-PCR) and by dual color fusion fluorescence in-situ hybridization (FISH). Archival blocs older than 4 years did not yield amplifiable RNA because of RNA degradation, whereas FISH analysis was feasible in all investigated cases. FISH analysis revealed COL1A1-PDGFB gene rearrangement in all DFSP cases (n=7), whereas RT-PCR could detect the COL1A1-PDGFB fusion transcript only in 1 DFSP. Two cases were negative. In 4 archival cases with storage between 4.5 and 12 years, RNA had been degraded making these cases unsuitable for RT-PCR. In PDF/DH, both RT-PCR and FISH analysis did not reveal any evidence of COL1A1-PDGFB gene rearrangement. We show that PDF/DH and superficial (plaque-like) DFSP, subtle clinicopathologic differences notwithstanding, are morphologic look-alikes that can be kept apart by molecular studies of the COL1A1-PDGFB gene fusion. For the detection of the COL1A1-PDGFB gene rearrangement in diagnostically difficult cases, RT-PCR and FISH analysis are reliable and helpful diagnostic tools. In archival formalin-fixed paraffin-embedded tissue, however, FISH analysis is more robust and exhibits a higher clinical sensitivity than RT-PCR.

Plaque-like CD34-positive dermal fibroma ("medallion-like dermal dendrocyte hamartoma"): clinicopathologic, immunohistochemical, and molecular analysis of 5 cases emphasizing its distinction from superficial, plaque-like dermatofibrosarcoma protuberans.

Soft-Tissue Tumours and Tumour-like Conditions

Dermal dendrocyte hamartomas are extremely rare; only two examples have been described with clinical features different from our cases and with incomplete immunohistochemical characterization. We report three female patients presenting a medallion-shaped, well-defined, slightly atrophic and asymptomatic congenital lesion. All 3 patients showed a fusiform-cell proliferation. Immunohistochemistry was positive for CD34, factor XIIIa, and fascin. Electron microscopy showed typical features of dermal dendrocytes. We believe that the lesions described represent a new, clinically and histopathologically distinct lesion originating in dermal dendrocytes. We propose to name it medallion-like dermal dendrocyte hamartoma.

Medallion-like dermal dendrocyte hamartoma: A new clinically and histopathologically distinct lesion

Background: Pityriasis rosea is an acute disseminated rash of unknown etiology and prolonged duration, characterized by erythematoussquamous plaques Despite having an ostentatious clinical picture for both the patient and family, it is self-limited and usually resolves without sequelae Pityriasis rosea is often erroneously diagnosed as mycosis and given unnecessary treatment

/pdf/pitiriasis-rosada-un-exantema-que-debe-ser-reconocido-por-el-1qq6st8obi.pdf

María del Mar Sáez-de-Ocariz

Papers

Medallion-like dermal dendrocyte hamartoma: A new clinically and histopathologically distinct lesion

Pitiriasis rosada: un exantema que debe ser reconocido por el médico de primer contacto. Estudio de 30 casos

Erythema and Induration at BCG Site in IPEX Syndrome