Cellular subcutaneous tissue. Anatomic observations

INTRODUCTION: We showed in a companion paper that the definition of the French "subcutaneous cellular tissue" considerably varied from the 18th to the end of the 20th centuries and has not yet reached a consensus. To address the anatomic reality of this "subcutaneous cellular tissue", we investigated the anatomic structures underlying the fat tissue in normal human skin. METHODS: Sixty specimens were excised from the surface to the deep structures (bone, muscle, cartilage) on different body sites of 3 cadavers from the Institut d'Anatomie Normale de Strasbourg. Samples were paraffin-embedded, stained and analysed with a binocular microscope taking x 1 photographs. Specimens were also excised and fixed after subcutaneous injection of Indian ink, after mechanic tissue splitting and after performing artificial skin folds. RESULTS: The aspects of the deep parts of the skin greatly varied according to their anatomic localisation. Below the adipose tissue, we often found a lamellar fibrous layer which extended from the interlobular septa and contained horizontally distributed fat cells. No specific tissue below the hypodermis was observed. Artificial skin folds concerned either exclusively the dermis, when they were superficial or included the hypodermis, but no specific structure was apparent in the center of the fold. India ink diffused to the adipose tissue, mainly along the septa, but did not localise in a specific subcutaneous compartment. DISCUSSION: This study shows that the histologic aspects of the deep part of the skin depend mainly on the anatomic localisation. Skin is composed of epidermis, dermis and hypodermis and thus the hypodermis can not be considered as being "subcutaneous". A difficult to individualise, fibrous lamellar structure in continuity with the interlobular septa is often found under the fat lobules. This structure is a cleavage line, as is always the case with loose connective tissues, but belongs to the hypodermis (i.e. fat tissue). No specific tissue nor any virtual space was observed below the skin. Thus, the commonly used term "subcutaneous cellular tissue" is inappropriate.     

Lipomatous metaplasia of superficial dermis

Lipomatous metaplasia is an uncommon phenomenon. After identifying the presence of a band of adipocytes in the superficial reticular dermis underlying two excisions for basal cell carcinoma, we prospectively reviewed all skin specimens accessioned in our laboratory over a 6‐month period and identified eight additional cases. In each example there was a band of adipocytes in the upper dermis, at the level of solar elastosis that was widely separated from the subcutaneous fat by a normal appearing reticular dermis. The cells were positive for S100 and negative for CD163. No connection between the superficial band of adipocytes and the subcutaneous or periappendageal fat was seen. The alterations were flat in configuration without polypoid changes. Eyerich et al. reported lipomatous metaplasia in the dermis of a patient with acute generalized exanthematic pustulosis and psoriasis, and postulated this to be a postinflammatory phenomenon. Fatty metaplasia occurs within a variety of cutaneous neoplasms including nevi, adnexal tumors and peripheral nerve sheath tumors. However, superficial dermal fatty metaplasia beneath cutaneous neoplasms is a newly described phenomenon and we suspect this process represents fatty metaplasia within solar elastosis and that it may occur more frequently than recognized.     

Lipomembranous changes and calcification associated with systemic lupus erythematosus

Lipomembranous changes are histological findings without specific clinical correlations, and are thought to be related to vascular impairment in fatty tissue. We describe a case of systemic lupus erythematosus (SLE) in which subcutaneous induration of the lower leg showed lipomembranous changes and calcification. This patient showed thrombophilia with thrombosis of the femoral and iliac veins, and cerebellar and myocardial infarction. A biopsy specimen from the subcutaneous tissue surrounding the multiple leg ulcers revealed degeneration of fat cells, lipomembranous changes in the fatty tissues, and calcification. Another biopsy specimen from the outer edges of the ulcers showed microthrombi and fibrinoid changes in the vessel walls, and mononuclear cell infiltrates in the dermis. Lipomembranous changes have been seen in connective tissue disorders such as lupus profundus, morphoea, systemic sclerosis, and panniculitis associated with dermatomyositis, but rarely associated with SLE. We speculate that ischaemic changes due to the vascular disturbance of the lower legs may have induced lipomembranous changes and calcification in the subcutaneous tissues in the present case.     

萎缩型隆突性皮肤纤维肉瘤二例

报道2例萎缩型隆突性皮肤纤维肉瘤.患者分别为16岁和24岁的男性,临床最初均表现为界限清楚的萎缩型红斑,逐渐在红斑基础上发生结节.病程分别为6年和5年.皮损组织病理检查显示表皮萎缩或正常,肿瘤细胞在真皮浅层呈波浪状排列,平行于表皮;肿瘤细胞在真皮下部呈席纹状、车幅状、编织状排列,并可见肿瘤细胞侵犯皮下脂肪,分割脂肪细胞.肿瘤细胞表达波形蛋白、CD34,不表达CD68和S100蛋白.

Abstract：

Two cases of atrophic dermatofibrosarcoma protuberans (DFSP) are reported.The patients were a 16-year-old and a 24-year-old boy with a clinical course of 6 and 5 years respectively.The lesions began as well-marginated atrophic erythema,and subcutaneous nodules appeared gradually on the erythema.Histopathology showed atrophic or normal epidermis,wavy arrangement of tumor (spindle) cells in the superficial dermis which was aligned parallel to the epidermis,storiform arrangement of tumor cells in the lower dennis,and typical lacelike pattern of infiltration of subcutaneous fat tissue with tumor cells.Immunohistochemistry showed that the tumor cells stained positive for vimentin and CD34,but negative for S100 or CD 68.     

Port-wine stains. Morphologic variations and developmental lesions

Studies have shown that port-wine stains (PWSs) probably represent a progressive ectasia of the superficial cutaneous vascular plexus. During examination of approximately 500 patients with PWSs, seven lesions were identified that could be categorized into two groups. In one group (two patients), the typical superficial PWS was accompanied by a proliferation and ectasia of thin-walled vessels in the deeper dermis, subcutaneous adipose tissue, and skeletal muscle (cavernous hemangioma). In the other group (five patients), single or multiple polypoid tumors arose that consisted of a proliferation of vessels with walls of varying thickness, and intervascular stroma (arteriovenous malformation). These tumors appear to arise in both young patients with flat lesions as well as the older patients with pronounced surface irregularities. Two patients were specifically chosen because they represented the typical PWS cobblestone pattern. This vascular abnormality represents a localized exaggeration of the ectasia process. We conclude that a small number of PWSs are associated with an underlying cavernous hemangioma. Furthermore, besides the surface irregularities that characterize the older PWS, de novo vascular tumors arise that can be categorized as arteriovenous malformations.     

Postirradiation pseudosclerodermatous panniculitis

Pseudosclerodermatous panniculitis is an unusual variant of panniculitis that results as a complication of megavoltage radiotherapy. Four women developed this unusual entity on the anterior chest and abdominal skin after receiving megavoltage therapy for either breast carcinoma or painful bone metastases from breast carcinoma. Histopathologically, the epidermis and dermis of the involved area showed little or no evidence of radiodermatitis. The main findings were confined to the subcutaneous tissue and consisted of thickened, sclerotic septa composed of both thick and thin collagen bundles, and a lobular panniculitis characterized by lipophagic granulomas and scattered lymphocytes and plasma cells. Additionally, one of the cases showed markedly dilated vascular spaces with the appearance of lymphatics in the upper part of the dermis. Pseudosclerodermatous panniculitis after irradiation is an unusual cutaneous complication of megavoltage radiotherapy that should be distinguished from subcutaneous metastatic disease, cellulitis, or connective tissue diseases involving the subcutaneous fat. The differential diagnosis can be established on the basis of the characteristic histopathologic features of postirradiation pseudosclerodermatous panniculitis.     

臀部巨大浅表脂肪瘤样痣一例

患者,女,34岁。左臀部肿物快速增大偶伴瘙痒1年。组织病理：真皮全层及皮下见多量小叶状分布的脂肪组织,成不规则分布,部分围绕血管生长,周围纤维结缔组织增生,可见群集或线状排列的脂肪细胞嵌入真皮胶原纤维中,真皮与皮下脂肪分界不明显或无分界。髋关节MRI平扫：左侧臀部皮下脂肪较对侧增厚,较厚处约7.5 cm,内未见明显异常信号影。诊断：浅表脂肪瘤样痣。予以手术切除,术后无复发。     

Angiomyxolipoma (vascular myxolipoma) of subcutaneous tissue

Three cases of angiomyxolipoma (vascular myxolipoma) have been published to date. We report an angiomyxolipoma located in the subcutaneous tissue of the scalp. Histologically, it consisted of an admixture of paucicellular myxoid areas and mature fat tissue, both containing numerous dilated blood vessels with hyalinized thin walls. The cells in the myxoid areas expressed CD34. This lesion requires differential diagnosis with other benign fat tissue tumors, especially myxoid spindle cell lipoma, superficial angiomyxoma, myxoid liposarcoma, and low-grade myxofibrosarcoma.     

Treatment options for giant congenital naevi

Giant congenital naevi (GCN) are disfiguring, potentially malignant pigmented naevi present at birth. The naevus cells in GCN are found throughout the dermis and sometimes penetrate the subcutaneous septa. It is claimed that superficial, more heavily pigmented and biologically different naevus cells reside in the upper dermis. Partial removal of these superficial naevus cells by dermabrasion, laser therapy, curettage or shave excision is less traumatic than excision surgery and produces an acceptable cosmetic result. However, none of these techniques or excision of GCN to superficial fat completely removes the risk of malignant transformation.     

Erythema nodosum leprosum: nature and extent of the cutaneous microvascular alterations

Skin biopsy specimens from four patients with erythema nodosum leprosum, when examined as Epon-embedded, 1-micron sections, exhibited a necrotizing vasculitis involving capillaries, venules, and small-to-medium arteries and veins. In the superficial dermis, affected venules and capillaries showed endothelial cell enlargement and focal necrosis associated with perivascular infiltrates of lymphocytes. In the deep dermis and subcutaneous tissue, affected venules, arterioles, and arteries exhibited endothelial cell necrosis and matted fibrin in the vessel walls associated with perivascular infiltrates of neutrophils. Throughout the dermis, mononuclear phagocytes with vacuoles containing numerous fragmented organisms were observed. By electron microscopy, electron-dense material resembling immune complexes was observed in the walls of these vessels. These observations support the concept that erythema nodosum leprosum is an immune complex-mediated necrotizing vasculitis involving capillaries, arterioles, arteries, venules, and veins.     

Painful Piezogenic Pedal Papules on a Child with Ehlers-Danlos Syndrome

A 5-year-old girl with Ehlers-Danlos syndrome developed painful piezogenic pedal papules. She had suffered from pain in her heels for the previous two years and had undergone extensive orthopedic examinations that revealed no abnormalities. On admission, she had typical signs associated with piezogenic pedal papules (PPP), with pain induced by standing and disappearance of the lesions and the pain on relief of pressure. These papules were due to herniation of subcutaneous fat into the dermis, possibly because of structural defects of the connective tissue. To the best of our knowledge, this is the first reported case of painful PPP occurring in childhood. We suggest that the herniation of subcutaneous fat in our patient was most probably due to the connective tissue defect that occurs in the Ehlers-Danlos syndrome.     

Atypical fibroxanthoma with perineural or intraneural invasion: report of two cases

We report two cases of atypical fibroxanthoma (AFX) that both had the previously unreported feature of neural invasion (one perineural and the other intraneural). AFXs recur in approximately 10% of cases but only rarely metastasize. Features associated with recurrence are inadequate excision and invasion into fat. Features associated with metastasis include recurrence, vascular invasion, deep tissue invasion, and tumor necrosis. Both of these tumors invaded deeply into subcutaneous fat and reached the deep fascia. Some authors would regard such cases as malignant fibrous histiocytoma (MFH) because of such deep extension; however, the concept of AFX as a superficial variant of MFH is outmoded--AFX is a distinct clinicopathologic entity with established clinical, histological, and immunohistochemical features.     

Cutaneous defects of focal dermal hypoplasia: an ectomesodermal dysplasia syndrome

The 5 major cutaneous defects of development found in focal dermal hypoplasia, an ectomesodermal dysplasia syndrome, are: aplasia cutis congenita, multiform atrophy-like areas, striate, papillomatous, and lipomatous lesions of skin. Subepidermal lipomatosis, present in some lesions, has been reported to be due to absence of dermis or a striking underdevelopment of connective tissue with replacement by adipose tissue from herniation of subcutaneous fat through multiple areas of hypoplasia. We believe this theory to be a major error in interpretation of the microscopic findings. We have had the unique experience of studying 2 patients periodically for 27-30 years and 2 additional patients for a shorter time. Biopsy specimens were removed at intervals for analysis from the same or similar lesions (43 specimens) from these 4 individuals. Our evidence strongly supports the concept that the cutaneous defects of development involving fat cells represent heterotopic fat i.e. a fat nevus resulting from dysplasia, not hypoplasia followed by herniation of subcutaneous fat.     

Research in practice: More than skin deep –aging of subcutaneous fat tissue

Mitochondria, responsible for the generation of energy in our cells, contain their own genome, mitochondrial (mt)DNA. It is known that mutations of mtDNA accumulate during normal aging and that this can be accelerated by oxidative stress, i.e. induced by ultraviolet radiation. These mutations are functionally relevant and they play a causative role in normal aging as well as premature aging induced by ultraviolet radiation. While the focus of scientific research was more on epidermis and dermis within the last years, alterations of subcutaneous fat tissue were not investigated thus far. Cockayne syndrome (CS) A and B are two proteins known to repair oxidatively induced DNA damage via nucleotide excision repair (NER) in the nucleus. We could show that these two proteins enrich in mitochondria upon oxidative stress, directly interact with mtDNA and the two repair‐associated proteins mtSSBP‐1 and mtOGG‐1 and protect from deletions of mtDNA. If CSA or CSB are lacking, mtDNA mutations accumulate particularly in the cells of subcutaneous fat tissue which appears to mediate loss of adipocytes via apoptosis. Therefore, the two NER‐associated proteins CSA and CSB appear to play a direct role in protection from mutations which in turn are causative in aging‐associated loss of subcutaneous fat tissue.     

Cryptococcal cellulitis in renal transplant recipients

We report three cases of cryptococcal cellulitis in renal transplant recipients and review five other cases in the literature. Seven cases of cryptococcal cellulitis occurring in other immunocompromised states are also reviewed and compared with the renal transplant group. Cryptococcal cellulitis in renal transplant recipients affects the skin of the extremities and is seen along with erythema, induration, tenderness, and superficial ulcerations of varying extent. Histopathologic examination shows either a variable lymphohistiocytic infiltration of the reticular dermis and subcutaneous fat or an acute panniculitis. Organisms may be difficult to find on routine sections, and special stains are recommended. Culture of tissue aspirate is an excellent method of diagnosis.     

Histological changes after treatment for localized fat deposits with phosphatidylcholine and sodium deoxycholate

Phosphatidylcholine (PPC) and sodium deoxycholate (DC) injections have been used cosmetically to reduce localized fat, but to date, few studies have addressed the histological effect of human fat tissue following injections of PPC and DC. We injected PPC and DC mixed with normal saline into the patient's abdominal area. Examinations of postinjection tissue revealed marked changes within the subcutaneous fat. We observed important microscopic evidence of substitution of fat by fibrosis, marked inflammatory infiltration with microabscess formation in the dermis, and septal and lobular panniculitis with thick fibrous septa. Fat necrosis with microcalcification and cyst formation were observed in the subcutaneous fat. Fibroid necrosis with extravasation was noted in the small vessels around fat necrosis. Therefore, careful use of PPC and DC is recommended when patients want to cosmetically reduce localized fat.     

Lupus erythematosus panniculitis presenting as palpebral edema and parotiditis

Lupus erythematosus panniculitis or lupus erythematosus profundus is characterized by inflammation of the deep dermis and subcutaneous tissue. It can occur in isolation or associated with chronic systemic or discoid lupus erythematosus. It usually consists of nodules and hardened subcutaneous plaques on the forehead, cheeks, proximal extremities, and buttocks. Periorbital and parotid involvement are rare and can lead to misdiagnosis. We present the case of a patient with lupus erythematosus panniculitis who presented with palpebral edema and involvement of the periocular fat and parotid gland.     

Desmoplastic fibroblastoma: a case presenting as a protruding nodule in the dermis

Desmoplastic fibroblastoma is a rare, benign, soft tissue tumor. We describe a case of superficial desmoplastic fibroblastoma presenting as a protruding nodule. A 41-year-old woman presented with a painless, firm, elevated nodule with ulceration on her left thigh. Histological examination from total excision showed a well-circumscribed tumor in the dermis, which comprised of spindle, oval and stellate cells arranged in a haphazard fashion, accompanied by abundant collagenous stroma and inconspicuous vasculature. Immunohistochemically, the tumor cells were positive for vimentin, and focally positive for alpha-smooth muscle actin and muscle-specific actin, but negative for CD34, S-100 protein, desmin and beta-catenin. We diagnosed this case as desmoplastic fibroblastoma arising in the dermis and superficial subcutaneous tissue.     

线状皮肤型红斑狼疮六例

目的 探讨线状皮肤型红斑狼疮（LCLE）临床和组织病理学特点。方法 回顾分析6例LCLE的临床和病理学特点。结果 LCLE多单侧发病,表现为带状或线状分布的暗红斑,伴毛细血管增生扩张,部分黏着性鳞屑。组织病理学诊断依据为真皮浅、深丛细血管周围及毛囊、皮脂腺、汗腺周围有致密团块状淋巴细胞浸润,部分病例可见表皮角化不全,毛囊角栓,基底细胞液化变性,类似盘状红斑狼疮组织像。治疗以氯喹为首选,对于皮疹范围较广泛,且组织病理改变见淋巴细胞浸润达真皮深部甚至皮下脂肪小叶处的患者,给予小剂量糖皮质激素治疗疗效明显。结论 LCLE诊断需要结合临床和组织病理。     

Nuclear DNA content in the cells of squamous cell carcinoma and Bowen's disease. II. A study on DNA contents of deeply invaded cells in comparison with non-invading cells at the upper dermis

To know the variation of DNA contents of SCC cells due to invasion activity, cytophotometric assay was used. The specimens for this study were paraffin-embedded tissue section of SCC stained with azocarmin G for blocking the non-specific fluorescence. By comparing the nuclear DNA content of tumor cells at the upper dermis and at the subcutaneous fat tissue, it was found that polyploid cells (greater than 4C and greater than 6C) populations in deep tissue was significantly higher than those in the upper dermis. This finding suggests that SCC cells capable to invade deeply are having larger amount of nuclear DNA that cells at the upper dermis.