A 4-year-old Boy with a Red Nodule on His Hand: A Quiz.

Sandgren EP, Palmiter RD, Heckel JL, Daugherty CC, Brinster RL, Degen JL. Complete hepatic regeneration after somatic deletion of an albumin–plasminogen activator transgene [Cell 1991;66:245–256

Experiments were conducted to study the effect of ageing of the host and senescence of the nodules on the content and composition of the proteins of leghemoglobin in nodules of cowpea (Vigna sinensis L.). Total and heme protein contents of leghemoglobin were the highest in the red nodules and dwindled with the onset of nodule senescence. In the fully senescent green nodules the total proteins decreased to a very low level, while the heme proteins were almost absent. Disc electrophoretograms of leghemoglobin obtained from red and brown nodules showed nine bands out of which only four gave positive test for heme. Greening of the nodules resulted in a considerable reduction in the intensity of the bands. Senescence of the host plant resulted in a reduction in the number of leghemo‐globin proteins in all types of nodules and brought about a drastic change in their electrophoretic mobility.

Twenty‐seven primary pituitary tumors (PPT) arose in 109 mice bearing transplanted pituitary glands (TPG). Several PPT were transplanted serially into isologous hosts. Transplanted pituitary tumors (TPT) from 79 different male or female hosts were obtained between 42 and 708 days after transplantation. Histological and electron microscopic preparations of the TPG, PPT and TPT were prepared. The TPG showed much cellular necrosis and diminished secretory activity during the first month. Cellular replacement and secretory granules reappeared after revascularization of the grafts and coincident with the reappearance of somatotrophic and mammotrophic activity in the female hosts. The TPG showed no significant growth for about 1 year and about 25% of the transplants became tumorous after 400 days. EM examination of the PPT revealed heterogeneous secretory granules resembling those of the alpha and beta type in the same cell. The endoplasmic reticulum (ER) was abundant and the mitochondria were large and many were structurally abnormal. The TPT usually grew slowly but differed from tumor line to tumor line. By six months after transplantation the TPT were polynodular, with red nodules and white nodules. In both red and white tumoral nodules, the cells were PAS, reticulin, amyloid, elastin and Masson‐negative, and showed some autoradiographic activity after proline‐H3 administration. Also, the EM shows no significant difference between the nodules. Fibrils about 70 Å in diameter were in the ER, and 100–300 Å in diameter in plasma fundamentalis, and fibers larger than 300 Å in extracellular areas. The fibrillar synthesis in the TPT cells was in inverse ratio to the granular secretory activity of the cells. Sixteen of the TPT in CB 815 and 87 hybrid mice contained C‐type virus‐like particles (VP). Viral particles were noted in the periphery of the nucleus, and in the endoplasmic reticulum. Cells with the most viral particles showed the least granular secretory activity. The TPT in females were mammotrophic, and in males prostatotrophic. The prostatic epithelial cells contain cytoplasmic organelles with delicate lamellae in fingerprint, whorl, or tubular arrangement and amorphous granular aggregates. Mice with TPT for several months had enlarged prostates, some having intraluminal hyperplastic trabeculae, and cells showing less secretory activity. In mice with two lines of TPT, C‐type viral particles appeared in the prostatic cells.

Observations were made on the content of α-aminoadipic acid and α-aminophimelic acid (DAP) in pea plants, nodules and Rhizobium leguminosarum, strain HT3. The preparations were purified by ion exchange chromatography, Qualitative analyses were made by paper chromatography, and quantitative analyses by means of an automatic amino acid analysator. In the whole plant and seeds the content of α-aminoadipic acid soluble in 70% ethanol varied between 10 and 80 μg/g dry weight. The shoot and red nitrogen fixing nodules contained more of this acid than roots and green inactive nodules. In the insoluble fraction of the shoot its concentration was 0.4-0.6 mg/g dry weight. α-Aminoadipic acid was not found in free living rhizobia, which again contained a considerable amount of α-aiaminopimelic acid, about 0.5 mg/g dry weight. The synthesis of DAP was intensive also in root nodules. In red nodules, which fixed molecular nitrogen, the content of DAP was 2.1 mg/g dry weight and in green inactive nodules 1.3 mg/g dry weight. It was shown that in the nodules DAP is closely connected with cell wall peptides of bacteroids. DAP could not be found in pea plants outside the nodules.

This case report describes an interesting example of a syringocystadenoma papilliferum lesion presenting in a 72-year-old man. He presented with a 10-month history of a red nodule in his umbilicus with unexplained weight loss and reduced appetite. The patient had a background of chronic obstructive pulmonary disease, treated prostate cancer and pemphigus vulgaris that had previously been treated with azathioprine. The nodule would occasionally bleed with trauma, but there were otherwise no associated symptoms. Physical examination revealed a 12 × 12 mm firm red nodule within the umbilicus with some creamy exudate overlying it. Given the clinical presentation, differentials at the time included Sister Mary Joseph nodule, amelanotic melanoma and pyogenic granuloma. A shave biopsy was arranged to help diagnose the nodule and further investigations including computed tomography (CT) and colonoscopy were undertaken. CT and colonoscopy did not indicate any sinister pathology. Histopathological findings demonstrated mildly cystic invaginations arising from a papillomatous epidermis that were lined by rows of cuboidal-to-columnar epithelial cells, with oval nuclei and a pale eosinophilic cytoplasm with squamous metaplasia. The stroma contained a dense mononuclear infiltrate, which was comprised predominantly of plasma cells and lymphocytes. The histopathological findings were of syringocystadenoma papilliferum. This report discusses the clinical and histopathologicial presentation of syringocystadenoma papilliferum and the investigations and management to consider with this diagnosis. We also discuss the various differentials that should be considered for a red nodule in the umbilicus.

To the Editor: A 72-year-old woman underwent radical excision of an adenocarcinoma of the right nasolacrimal duct. Postoperative radiation therapy (30 Gy) was added to the residual tumor, which, however, it was insufficient, and the tumor persisted at the external base of the skull. During admission, she was referred to our department complaining of a nodule on the abdomen. Physical examination showed a 5-mm-sized reddish nodule with erosion of the surface (Fig. 1A). A skin biopsy showed tumor nests connecting to the epidermis and extending downwards into the dermis (Fig. 1B). High-power magnification revealed small uniformly cuboidal cells with round deeply basophilic nuclei, which were connected by intercellular bridges. A few cystic or ductal structures were identified within the nests. Immunohistological examination showed strong expression of carcinoembryonic acid in the duct wall, and poroid cells were positive for epithelial membrane antigen. Gross cystic disease fluid protein-15 (GCDFP-15) was negative. Further clinical examination revealed additional reddish nodules on the trunk, neck, and extremities (Figs. 2A, B), which summed up to 10 in total. She complained that those nodules were increased in number after radiation therapy. All of them were surgically removed under local anesthesia. Histological examination revealed that all of them were compatible with the features of poroma. Histological examination showed anastomosing lobules of nests consisting of small, uniform, basophilic, and cuboidal poroid cells. Scattered ductal structures surrounded by the eosinophilic cuticular cells were also recognized. Notably, some of the poromas showed that the tumor nests were confined to the epidermis, indicating intraepidermal poroma (Fig. 2C). In contrast, others were those of Pinkus type. The tumor nests were surrounded with myxomatous stroma, which were highlighted by Alcian blue stain (Fig. 2D). Findings of peripheral palisading were absent in all the basophilic tumor islands.FIGURE 1: A reddish nodule on the chest (arrow). A, Surrounding erythema is allergic contact dermatitis due to adhesive tape. B, Histological features showing anastomosing lobules of tumor nests consisting of poroid cells.FIGURE 2: A and B, Reddish small nodules are scattered on the chest, neck, shoulders, and other areas on the trunk. C, Tumor nests were confined within the epidermis in some lesions. D, Tumor nests in the dermis were surrounded by myxomatous stroma, which was positively stained by Alcian blue stain.The most interesting feature in our case is the multiple occurrences of poromas after radiation therapy in a cancer-bearing patient. Poroma usually occurs as a solitary lesion or at most a few lesions. So far, several cases of multiple eccrine poromas have been reported, most of them occurred in patients with malignancies (Table 1).2–7 In particular, hematologic malignancies such as lymphoma or leukemia have been seen.6,7 In other cases, poromas arised on the irradiated sites5–7 or occur following chemotherapies.7 Our case rapidly developed multiple poromas after radiation therapy, although the occurrence sites were not the irradiated sites. In addition to hematologic malignancies, there also reports of poromas developing after bone marrow transplantation and subsequent graft versus host disease.7 Our case presented with not hematologic malignancy but invasive solid cancer. There was no evidence of either lymph node or distant metastases. The development of multiple poromas may be secondary to immunosupression.TABLE 1: Multiple Eccrine PoromasAnother interesting point was that the poromas exhibited different histological patterns, although presented similar clinical features. Some of them showed the features of common Pinkus type, while the others showed intraepithelial nests, namely intraepidermal poromas. The behavior of all the resected poromas was benign. Additionally, the stroma surrounding the poroma nests was myxomatous in some of the lesions showing mucin deposition which was highlighted by Alcian blue stain. Mucinous stroma is not a common finding in poromas. In conclusion, we report a case of multiple poromas in a patient with invasive carcinoma. The patient was not treated with chemotherapy, but eruptive poromas occurred after radiation therapy. The occurrence of multiple poromas may be related to immunosupression.

BackgroundBehcet’s disease (BD) is an inflammatory disorder of unknown cause that is characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. Local vasculitis can cause damage to the visceral system, but it is rare in kidney patients, especially those with IgA nephropathy (IgAN). In China, a small number of related cases have been reported. Here we present a case of co-occurrence of BD and IgAN.Case presentation: An 18-year-old female who presented with a history of recurrent oral ulcers was found ten years ago. Four years later, the patient presented with reddish nodules on the skin of both lower limbs and then presented with vulvar ulcers. This patient was clinically diagnosed with Behcet’s disease after left calf skin biopsy and presented severe proteinuria and hematuria during this period. IgAN was diagnosed after percutaneous renal biopsy. The patient was treated with hormonal, anti-inflammatory, immunomodulatory, kidney protective, and protein-lowering urine agents. After 3 years of follow-up, the patient reappears oral ulcers, reddish nodules on the skin of both lower limbs and renal dysfunction.ConclusionsBD is less common in China and is clinically prone to missed diagnosis and misdiagnosis. BD with IgAN is rarer. We should regularly pay attention to the routine urine and renal function of BD patients for early detection and treatment and to prevent further progression of the disease.

A 78-year-old white woman returned for a routine 6-month skin cancer examination. She had a history of actinic keratosis and multiple basal cell carcinomas. She had no personal or family history of dysplastic nevi or melanoma. The patient was asymptomatic and unaware of any new or changing skin lesions. The patient had multiple lentigines, hemangiomas, and actinic and seborrheic keratoses on all sun-exposed areas. There were no less than 10 seborrheic keratoses on the right mid-back, and one was found to have a 1-cm, reddish nodule asymmetrically located within it (Figs 1 and 2). A clear papule on the left preauricular area was found on biopsy to be a basal cell carcinoma. The nodule on the back was still present 1 month later and it was felt that further evaluation was indicated. As melanoma has been reported to develop in seborrheic keratoses, we decided to examine the lesion using digital dermoscopy. With digital dermoscopy, a well-demarcated reddish nodule was asymmetrically located within a brown lesion. It blanched significantly with pressure. Within the nodule, there were dotted and irregular linear vessels (atypical vascular pattern; also known as polymorphous vascular pattern) and regular-appearing brown dots. Surrounding the reddish nodule, there were pale and pigmented, comedo-like openings, fissures, and ridges (brain-like appearance). Some of the follicular openings appeared to be within the wall of the nodule (Figs 3 and 4). Comedo-like openings, fissures, and ridges are primary dermoscopic criteria for the diagnosis of a seborrheic keratosis; however, the vascular pattern seen has not been reported in seborrheic keratosis. Due to the patient's age and the rarity of significant pathology arising in a seborrheic keratosis, a shave biopsy was performed. To our surprise, the specimen was interpreted by an experienced dermatopathologist as a well-differentiated eccrine porocarcinoma. Due to the high local recurrence rate and metastatic potential of this carcinoma, the patient was referred for Mohs' surgery. Both the basal cell carcinoma and the eccrine porocarcinoma were excised in one stage. A metastatic work-up was negative and the patient appears to be doing well.

BackgroundDermatofibrosarcoma protuberans (DFSP) is a rare, low- to intermediate-grade sarcoma, which represents a diagnostic imaging challenge.This study aimed to analyze the clinical and ultrasound features of primary and recurrent DFSP to improve the diagnosis.MethodsClinical, imaging, and pathological data from a total of 58 patients (23 patients with primary DFSP and 35 patients with recurrent DFSP) were retrospectively reviewed.ResultsThere was no statistically significant difference in age, sex, tumor size, or echogenicity between the two groups. Most of the primary DFSP lesions involved the overlying dermis and hypodermis, while most of the recurrent DFSP lesions were fixated to more deeply seated structures at the original surgical incision. Red nodules on the skin were found more frequently in the primary group. There were statistically significant differences in the type of lesion and ultrasound tumor morphology (p < 0.050). The lesions in the primary group showed more tentacle-like projections or a “claw” sign, while the lesions in the recurrent group were more commonly oval, lobulated, and irregularly shaped. Hypervascularity was common in both groups.ConclusionsFor primary DFSP, a slow-growing, red nodule on the skin involving the overlying dermis and hypodermis, more frequently a hypoechoic mass with tentacle-like projections or a “claw” sign, was observed. For recurrent DFSP, palpable subcutaneous nodules or subcutaneous masses at the original surgical incision and oval, lobulated, and irregularly shaped lesions were more commonly observed. This may be useful for improving diagnostic accuracy.

A 77-year-old man with a history of surgical resection of malignant melanoma involving the fifth toe of his left foot 14 years ago presented at the Kariya Toyota General Hospital with a 3-month history of skin ulcer at the same site and red nodules on the lower left leg. Malignant melanoma was suspected, and the patient was referred to our department. On examination, a skin ulcer measuring 25 × 20 mm was observed at the amputation site on the left foot. In addition, multiple red nodules were observed on the lower left leg. Skin biopsies of the ulcer and nodules revealed recurrent malignant melanoma with in-transit metastasis. Two weeks later, he developed acute myocardial infarction and was hospitalized at the Kariya Toyota General Hospital. One month later, the myocardial infarction ameliorated, and he was transferred to our department. As the myocardial infarction had decreased the patient's tolerance to surgery, interferon-β was administered by intravenous infusion. The skin ulcer and red nodules on the lower left leg disappeared 26 weeks after infusion had been initiated. The patient's progress has been satisfactory, with no evidence of recurrence or metastasis at 1 year and 9 months after the initiation of intravenous infusion.

A 63-year-old woman living in the countryside referred to our department with a 2-month history of a red nodule localized on the right breast. Histological examination, immunohistochemical analyses and serologic evaluation conducted with ELISA and Western blot were performed. Clinical diagnosis of borrelial lymphocytoma was not possible solely on the clinical presentation of a classical nodular form without lymphoadenopathy. An absence of a referred prior tick bite and a previous or concomitant erythema migrans at clinical presentation rendered a more challenging diagnosis. The fact that the patient lived in the countryside, the appearance of the breast nodule in September, and serologic, histologic, and immunohistochemical analysis facilitated the diagnosis of borrelial lymphocytoma. We report this case to highlight the importance of an investigation of Lyme borreliosis when a patient living in the countryside presents with a red nodule of the nipple and areola.

Recent studies have analysed the impact of Merkel cell polyomavirus (MCPyV) on the clinical features and prognosis of patients with Merkel cell carcinoma (MCC). However, there are currently no available data on specific morphological clinical differences of MCC according to MCPyV-positive (MCPyV+) and -negative (MCPyV-) status and any possible prognostic implications of the different clinical presentations. To describe the clinicopathological characteristics of patients with MCC and the prevalence of MCPyV infection in an Italian cohort of patients and to define possible differences in clinicopathological and prognostic features among MCPyV+ and MCPyV- MCCs. A retrospective, multicentre cohort study was conducted in two Italian tertiary referral centres. MCPyV presence was detected by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) with two different primer sets, amplifying the viral protein (VP1) or large T antigen (LT) viral regions (VP1-PCR and LT-PCR, respectively). Clinicopathological features were compared between MCPyV+ and MCPyV- tumours and between red exophytic nodules and subcutaneous cyst-like MCCs. Of the 62 MCCs that were included, 43 (69%) presented as red exophytic nodules and 12 (19%) with a subcutaneous cyst-like appearance; MCPyV was detected in 25 cases (40%) by IHC, 35 (56%) by VP1-PCR and 49 (79%) by LT-PCR. No correlation was found between clinical morphology and viral status. Mortality rate was higher for MCPyV- cases (77%) than for MCPyV+ (23%) (P = 0.239) and higher for red nodules (70%) than for cyst-like lesions (59%) (P = 0.005). By multivariable analysis, age at diagnosis, Ki67 proliferation index and treatment with surgery/radiotherapy remained the only factors significantly affecting overall survival. This study highlights the potential impact of clinical morphology of MCCs on prognosis. Subcutaneous cyst-like morphology may provide a survival benefit to the patients, regardless of MCPyV status.

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is defined as anaplastic large cell lymphoma localized to the skin without extracutaneous involvement at the time of diagnosis. Histologically, PCALCL is characterized by a dense nodular infiltrate of large lymphocytes, extending into the deep dermis or subcutis. Epidermotropism is sometimes, but not frequently, seen. We herein report a case of PCALCL with prominent epidermotropism. A 63-year-old Japanese woman was referred to our hospital with a red nodule and indurated erythema in 1997. Histological findings of a skin biopsy specimen from a red nodule were typical of PCALCL, however, biopsy specimens from indurated erythema showed remarkable epidermotropism. Tumor cells were positive for CD4, and CD30, but negative for CD3 and CD8. She was diagnosed with PCALCL. In 2007, skin biopsy was performed again, which showed large atypical lymphocytes in the upper dermis with mild epidermotropism. Tumor cells expressed in both CC chemokine receptor 4 and CXC chemokine receptor 3, which may explain prominent epidermotropism in this case.

Merkel cell carcinoma (MCC) is a cutaneous carcinoma with neuroendocrine differentiation. It arises typically on sun-exposed areas of elderly men as an asymptomatic, rapidly growing, red nodule. Although it is usually found as a solitary nodule, in almost one third of cases MCC may be associated with other malignancies such as basal cell or squamous cell carcinomas. Merkel cell carcinoma should be considered as differential diagnosis every time we have a rapidly growing, red nodule, arising in an elderly patient with signs of sun-damage. We report a case of MCC developing in association with a pre-existing Bowen's disease. The association between MCC and Bowen's disease is quite common and their area of occurrence is usually a sun-exposed area. Ultraviolet radiation contributes to the etiology of both the malignancies.

Analysis of CXCL9 and CXCR3 expression in a case of intravascular large B-cell lymphoma