Early regression index (ERI) on MR images as response predictor in esophageal cancer treated with neoadjuvant chemo-radiotherapy: Interim analysis of the prospective ESCAPE trial.

PURPOSE: The early regression index (ERI) predicts treatment response in rectal cancer patients. Aim of current study was to prospectively assess tumor response to neoadjuvant chemo-radiotherapy (nCRT) of locally advanced esophageal cancer using ERI, based on MRI. MATERIAL AND METHODS: From January 2020 to May 2023, 30 patients with esophageal cancer were enrolled in a prospective study (ESCAPE). PET-MRI was performed: i) before nCRT (tpre); ii) at mid-radiotherapy, tmid; iii) after nCRT, 2-6 weeks before surgery (tpost); nCRT delivered 41.4 Gy/23fr with concurrent carboplatin and paclitaxel. For patients that skipped surgery, complete clinical response (cCR) was assessed if patients showed no local relapse after 18 months; patients with pathological complete response (pCR) or with cCR were considered as complete responders (pCR + cCR). GTV volumes were delineated by two observers (Vpre, Vmid, Vpost) on T2w MRI: ERI and other volume regression parameters at tmid and tpost were tested as predictors of pCR + cCR. RESULTS: Complete data of 25 patients were available at the time of the analysis: 3/25 with complete response at imaging refused surgery and 2/3 were cCR; in total, 10/25 patients showed pCR + cCR (pCR = 8/22). Both ERImid and ERIpost classified pCR + cCR patients, with ERImid showing better performance (AUC:0.78, p = 0.014): A two-variable logistic model combining ERImid and Vpre improved performances (AUC:0.93, p < 0.0001). Inter-observer variability in contouring GTV did not affect the results. CONCLUSIONS: Despite the limited numbers, interim analysis of ESCAPE study suggests ERI as a potential predictor of complete response after nCRT for esophageal cancer. Further validation on larger populations is warranted.

Trichoblastic carcinoma: a report of two cases of a deeply infiltrative trichoblastic neoplasm.

BACKGROUND: Trichoblastoma is a benign neoplasm with primitive hair follicle differentiation. The tumor is characterized by nests and cords of epithelial cells in an organized relationship with stroma. Some of the epithelial cells resemble follicular germ and other cells show follicular sheath differentiation. The neoplasm is symmetrical and well circumscribed. In addition, cytologic examination shows no atypia. Concept of its malignant counterpart is poorly understood. OBJECTIVE: We report two trichoblastic neoplasms that show histologic features of malignancy. METHODS: Skin biopsies from the lip region of a 53-year-old female and a 74-year-old male who had presented with the neoplasms in that location for several years were reviewed. Excised specimens measured 2 x 1 x 1 cm and 1.6 x 0.7 x 0.8 cm respectively. RESULTS: The histologic sections revealed locally aggressive neoplasms showing prominent differentiation towards hair germ and follicular sheath with formation of papillary mesenchymal bodies, follicular bulb-like structures, small keratin cysts and rare malformed hair shaft. The neoplasm showed asymmetry of architecture and massive subcutaneous and muscular infiltration. CONCLUSION: With demonstration of these two cases and references of few other reported cases we raise the possibility of existence of trichoblastic carcinoma that is distinct from basal cell carcinoma.

Dermatofibroma-like granular cell tumor.

BACKGROUND: There have been several reports in the literature of dermatofibromas with granular cells. Here we report a granular cell tumor with the architecture of a dermatofibroma. This is the first report of this histological variant of granular cell tumor. The lesion was a 2.5-cm oval, hyperpigmented plaque present for "years" on the back of a 60-year-old African-American woman. METHODS: The specimen was processed using formalin fixation and paraffin embedding. Tissue sections were stained with hematoxylin and eosin. Immunohistochemical studies were performed with antibodies directed against S-100 protein, neuron-specific enolase, and factor XIIIa. RESULTS: Histopathologic examination revealed granular cells, some of which were spindle shaped, distributed singly and in small groups between collagen bundles resembling a dermatofibroma. Immunohistochemical studies showed the tumor cells to be positive for S-100 and neuron-specific enolase and negative for factor XIIIa. CONCLUSION: The immunohistochemical findings support the diagnosis of a granular cell tumor with a dermatofibroma-like pattern.

Solitary fibrous tumor of the vagina.

We report of a solitary fibrous tumor (SFT) of the vagina and discuss the differential diagnosis. This is the first SFT documented, to our knowledge. SFTs should be included in the differential diagnosis of fibroblastic, myofibroblastic, and neural lesions of the skin, subcutaneous tissue, and mucosa and can be distinguished from other spindle cell neoplasms at those sites.

Nodular tertiary syphilis mimicking granuloma annulare.

We describe a 47-year-old man with annular plaques on the arms and torso that were treated as granuloma annulare, based on clinical and histopathologic findings. Exacerbation of the lesions during treatment with topical corticosteroids prompted a search for an infectious cause, which proved to be syphilis in the tertiary stage. The clinician should maintain a high index of suspicion for syphilis in the differential diagnosis of unusual annular skin lesions in a patient with noncaseating granulomas seen on skin biopsy.

Inflammatory myofibroblastic tumor of the skin.

We report a case of inflammatory myofibroblastic tumor (IMF) of the skin in a female with a history of Wegeners granulomatosis. The patient had a painless, erythematous, and indurated lesion of the left elbow. The resected specimen revealed a 4 cm x 3 cm nodule involving the entire dermis and superficial portions of subcutis with a stellate profile at scanning magnification. There were spindle cells in fascicles and whorls and a mixed inflammatory cell infiltrate of plasma cells, lymphocytes, neutrophils, and eosinophils. The spindle cells were immunoreactive for vimentin, muscle specific actin, and smooth muscle actin. The polyclonal and polymorphous nature of the inflammatory cells was confirmed by immunohistochemical studies. This is the first case of IMF of the skin documented by immunostaining.

Purpura as a cutaneous association of sickle cell disease.

A common chronic feature of sickle cell disease is the presence of painful, punched-out leg ulcers. Other cutaneous findings in patients with homozygous sickle cell disease have not been described in the literature. We present a case of a 50-year-old black woman with sickle cell disease who was admitted for acute onset of arm and hip pain. After admission she deteriorated clinically, with multiorgan failure and mental status changes. Examination of the skin revealed erythematous papules and plaques with scaly centers and purpura on the upper trunk. The clinical differential diagnosis was vasculitis versus sepsis. Skin biopsy of two representative lesions was performed. Hematoxylin- and eosin-stained sections showed a superficial perivascular mixed inflammatory infiltrate with numerous eosinophils and extravasated erythrocytes, some of which exhibited bizarre morphology of sickled red blood cells. These findings indicated that the patient's cutaneous lesions, possibly multifactorial in origin, could be a component of her sickle cell crisis. This case is presented as an unusual one in which evaluation of erythrocyte morphology contributed to patient management and to emphasize the importance of examining erythrocyte morphology as a part of the histologic evaluation of stained tissue.

Calciphylaxis associated with metastatic breast carcinoma.

Calciphylaxis is a rare disorder associated with calcification of small- and medium-sized blood vessels, and progressive skin necrosis usually seen in the setting of end-stage renal disease (ESRD) and secondary hyperparathyroidism. It has also been observed in primary hyperparathyroidism, hypercalcemia of malignancy (extensive bony metastasis of breast cancer), and an isolated case reported with end-stage liver disease. We report an unusual case of calciphylaxis associated with metastatic breast carcinoma in the absence of renal or parathyroid disease. Calciphylaxis has generally been associated with end-stage renal disease and hyperparathyroidism. One previous case report described calciphylaxis occurring in a patient with metastatic adenocarcinoma of the breast and hypercalcemia. Our case represents the second reported case of calciphylaxis associated with osteolytic, metastatic breast cancer. Although ESRD with secondary hyperparathyroidism is the most common presentation of calciphylaxis, this case demonstrates that other conditions that alter normal calcium metabolism must be considered in the differential diagnosis.

Neurofollicular hamartoma with strong diffuse S-100 positivity: a case report.

Neurofollicular hamartoma is a recently described lesion with a distinct pilosebaceous and spindle cell proliferation. Neurofollicular hamartoma is composed of spindle cells haphazardly arranged in a fibromyxoid stroma closely associated with an abnormal hyperplasia of folliculosebaceous units. Although this histologic pattern has been classified as "neurofollicular," all cases reported thus far have had only scattered spindle cells with S-100 positivity. We present a case of neurofollicular hamartoma with strong and diffusely positive staining of spindled cells for S-100 protein. This lesion also shows scattered positivity of spindle cells for monoclonal neuron specific enolase and synaptophysin. We interpret the results of immunostains of this lesion as evidence for neural differentiation. This case validates the concept of "neurofollicular" hamartoma.

Tissue-conserving surgery for prognosis, treatment, and function preservation.

OBJECTIVES: To describe an approach based on initial tissue-conserving surgery used to obtain histologically determined prognostic information that has therapeutic implications and the potential to enhance preservation of function. STUDY DESIGN: Analysis of a group of patients with head and neck cancer treated initially with tissue-conserving surgery based on Mohs' histographic sectioning and selected neck dissection to derive histologically determined prognostic information with therapeutic implications and preservation in function. METHODS: This study is primarily based on an analysis of patients from January 1, 1989, through June 4, 1996 assigned to a protocol evaluating resection of oral cavity squamous cell cancer with margin control using Mohs' histographic technique and/or a group of patients with neck assessment of NO on clinical examination who are undergoing supraomohyoid neck dissections. RESULTS: Thirty-three primary tumor resections were performed using the Mohs' technique, and 54% required two or more Mohs' sections before clear histologic margins were obtained following resection based on clinically determined negative margins. There were 44 patients who underwent unilateral or bilateral supraomohyoid neck dissections, and 33% had occult, histologically positive nodes. When compared with the disease of the neck specimens, a preoperative computed tomography scan had a sensitivity of 25%, a specificity of 77%, and an accuracy of 63%. CONCLUSIONS: This report describes the effectiveness of Mohs' histographic sectioning and selective neck dissection as a means of determining prognostic information that can be used to develop a focused and cost-effective treatment program that, along with contemporary reconstructive techniques, provides a potential enhancement of function preservation.

Sebaceous neoplasm with reticulated and cribriform features: a rare variant of sebaceoma.

Troy and Ackerman defined the term sebaceoma (Am J Dermatopathol 1984: 6: 7-13) as benign neoplasm of basaloid cells with varying numbers of mature sebocytes. Steffen and Ackerman (Neoplasms with sebaceous differentiation. Philadelphia: Lee and Febiger, 1994: 401-425) illustrated many examples of sebaceoma, two of which had a reticulated and cribriform pattern. We report a case of sebaceoma from the scalp of a 52-year-old white female. Histologically, it displayed reticulated and cribriform basaloid epithelial islands. This is the third reported case of sebaceoma, to our knowledge, with these unusual features.

Isotretinoin and recombinant interferon alfa-2a therapy of metastatic malignant melanoma.

Twenty-five patients with metastatic malignant melanoma were treated with isotretinoin (13-cis-retinoic acid) orally at 1 mg/kg daily and recombinant interferon alfa-2a (INF-alpha) subcutaneously at 3 million units daily for 16-48 weeks. Therapy was well tolerated; fatigue and hyperlipidemia were the most frequent dose-limiting toxicity and necessitated dose reductions in 14 patients. Two patients achieved a complete response, and 3 responded partially for a total response rate of 20% (95% confidence interval: 4-36%). Responses occurred primarily in patients with limited tumor burden and disease confined to the skin and lymph nodes. Significant elevations in peripheral blood 2'-5'-oligoadenylate synthetase activity and natural killer activity were observed with therapy. The magnitude of these changes, however, was not predictive of response. Biopsy specimens of two responding lesions showed extensive necrosis of tumor. One specimen showed large aggregates of melanophages in association with tumor. The combination of isotretinoin and IFN-alpha is an active, easily administered regimen with acceptable toxicity for metastatic malignant melanoma.

Interleukin-1alpha gene expression during wound healing.

Interleukin-1alpha is known to be constitutively produced by epidermal keratinocytes under normal conditions, and injection of this cytokine enhances wound reepithelialization. However, no studies have characterized the temporal sequence of interleukin-1alpha gene expression over the time course of wound healing, and the cellular sources of this cytokine have not been identified. In the present studies, levels of interleukin-1alpha messenger RNA in wound tissue isolated from SKH-1 hairless mice were characterized and the cells that produced interleukin-1alpha immunoreactive protein over a 10-day time course of wound healing were defined. A time-dependent upregulation in interleukin-1alpha gene expression occurred immediately (4 hours) after a full-thickness wound was made, which represented a four-fold increase over levels of cytokine gene expression detected in nonwounded skin. Upregulation of cytokine gene expression correlated with an immediate increase in plasma interleukin-1alpha levels and was followed by an increase in interleukin-1alpha immunoreactive protein localized to keratinocytes within the leading edge of the wound and epidermis, as well as to neutrophils within the dermis. The rapid increase in local and systemic interleukin-1alpha levels correlated with the infiltration of a significant number of neutrophils into the wound site and with the proliferation of both basal keratinocytes and dermal fibroblasts. Given the known ability of interleukin-1alpha to regulate proliferation and migration of epidermal keratinocytes and to indirectly induce leukocyte chemotaxis, the results of the present studies suggest that interleukin-1alpha may be an important cytokine with both local and systemic actions that are linked to the initiation of critical cellular events early in wound healing.

Spindle cell hemangioendothelioma: a neoplasm associated with Maffucci's syndrome.

A case of a 21-year-old male with Maffucci's syndrome is presented in which the patient developed multiple cutaneous spindle cell hemangioendotheliomas (SHE). Recent reports suggest an association between spindle cell hemangioendotheliomas (SHE) and Maffucci's syndrome. Our case supports the interpretation that SHE is associated with Maffucci's syndrome.

Sclerosing B-cell lymphoma involving the skin.

We report a case of sclerosing B-cell lymphoma involving the skin. The patient is a 43-year-old man who came to our institution with a 4-year history of multinodular masses in the back. A thoracic CT scan demonstrated subcutaneous masses with extension to the posterior parietal pleura and compression of several epidural spaces. An incisional biopsy was performed and demonstrated an infiltrative process in the lower dermis composed of interconnected thick sclerosing bands forming compartments around groups of large neoplastic cells. These neoplastic cells were shown to be B lymphocytes using immunohistochemical stains. A diagnosis of diffuse sclerosing B-cell lymphoma, large cell type, was made. Our case is reported to alert dermatologists and dermatopathologists to the occurrence of this neoplasm in the skin which could be confused with a deep inflammatory process or other neoplastic conditions.

Granulocyte-macrophage colony stimulating factor gene expression and function during tumor promotion.

Although recent evidence suggests that granulocyte-macrophage colony stimulating factor (GM-CSF) plays a role in cutaneous inflammation induced by topical exposure of phorbol ester tumor promoters to murine epidermis, there is little information available on the temporal sequence of gene expression of this cytokine over the time course of tumor promotion or about its function in this process. The goal of the present studies was to examine the potential role of GM-CSF in tumor promotion in SENCAR mice. Competitive reverse transcriptase polymerase chain reaction (RT-PCR) studies demonstrated that a single topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA; 2 micrograms, 10 micrograms) to the dorsal epidermis of SENCAR mouse skin stimulated a dose and time dependent GM-CSF gene expression that was upregulated at 1 h after TPA exposure, peaked at 3 h and declined at 12 h. Although treatment with 7',12'-dimethylbenz[a]anthracene (DMBA) did not stimulate GM-CSF gene expression, GM-CSF gene expression was elevated in epidermal tissue isolated from SENCAR mice treated with a single application of 10 nmol DMBA followed by multiple applications of 2 micrograms TPA over a 1-22 week time course. Immunochemical and autoradiographic studies demonstrated that GM-CSF protein was produced by suprabasal keratinocytes, interfollicular cells, nonproliferating papilloma cells and leukocytes within the dermis. Intraperitoneal injection of recombinant (r) GM-CSF into SENCAR mice at 2 h prior to topical application of 10 micrograms TPA induced a significant increase in epidermal keratinocyte proliferation, leukocyte infiltration into the dermis, hydroperoxide production by circulating neutrophils and chemotactic activity present within the plasma at 24 h compared to treatment with only 10 micrograms TPA. Intravenous injection of anti-GM-CSF antibodies significantly inhibited both local and systemic inflammatory events induced by topical application of TPA. The present studies suggest that GM-CSF has a broad spectrum of activity with at least two target cell populations, epidermal keratinocytes within the proliferative compartment and leukocytes. This cytokine is actively transcribed during the tumor promotion process, acts as a signal peptide that stimulates epidermal proliferation, primes circulating neutrophils to produce hydroperoxide and regulates leukocyte migration.

Metastatic Crohn's disease. A rare cutaneous manifestation.

Cutaneous extraintestinal manifestations of Crohn's disease are common. Lesions contiguous with the gastrointestinal tract, such as perianal, peristomal, and perifistular inflammation are characterized by the histologic demonstration of granulomas. Rarely a cutaneous granulomatous lesion occurs that is noncontiguous with the gastrointestinal tract and is separated from it by normal skin. We report axillary "metastatic" Crohn's disease that appeared with exacerbation of the inflammatory bowel disease and responded well to steroid therapy.

Malignant melanoma with osteoid formation.

We report a case of malignant melanoma with osteoid formation arising in a patient who had had a diagnosis of neurofibromatosis. The presence of osteoid was confirmed histochemically by the picrosirius-polarization method and by transmission electron microscopy. Osteoid formation in malignant melanoma is rare, with only three cases reported prior to ours. Neoplasms arising from derivatives of the neural crest are known to show areas of metaplastic differentiation and heterologous elements. Among neural tumors, malignant nerve sheath neoplasms in particular are noted to display such heterologous elements as rhabdomyoblasts, cartilage, osteoid, and bone. Such heterologous elements are much less common in malignant melanoma. Our case report is an unusual example of a neural crest-derived neoplasm with heterologous elements.