[Vascularized tumor of the retroauricular skin]. / Gefäßreicher Tumor der retroaurikulären Haut.

An 84-year-old female patient with loss of hearing and otorrhoea went to an otolaryngologist. On examination, a polypoid mass in the auditory canal and a retroauricular skin lesion, possibly seborrheic keratosis, were found. Only the skin was submitted for histological examination and showed a cutaneous highly vascular lesion with an associated "zellballen" of clear cells without atypia. The initial diagnosis was that of a cutaneous glomangioma. Immunohistochemical findings favored diagnosis of a paraganglioma. Additional clinical information revealed a large mastoid tumor mass. Therefore, the findings were compatible with an jugulotympanic paraganglioma with infiltration of the overlying skin. This possibility was initially not considered in differential diagnosis, as cutaneous glomangiomas are relatively common (typically located on the hands). Cutaneous paragangliomas, however, are not reported.

[Paratracheal lymph node with suspicion of carcinoma]. / Paratrachealer Knoten mit Karzinomverdacht.

Three paratracheal lymph nodes of a 20-year-old patient were submitted for examination, of which one showed numerous thyrocytes with large void nuclei and was suspected of being metastatic papillary thyroid carcinoma. The simultaneously resected thyroid gland, which was subsequently submitted showed findings consistent with Hashimoto's autoimmune thyroiditis (AIT). In the context of the resected goiter tissue, the suspected lymph node metastasis was identified as a hyperplastic ectopic (so-called parasitic) goiter nodule with thyrocytic changes typically seen in Hashimoto's AIT, such as oxyphilic cell alterations and a high plasma cell content. The re-examination of the suspicious lymph node revealed complete lack of a marginal sinus, thus excluding the diagnosis of a lymph node as well as the diagnosis of thyroid carcinoma metastasis.

[History of dermatopathology]. / Geschichte der Dermatopathologie.

Hebra in Vienna and later Unna in Hamburg are considered to be the protagonists of academic dermatopathology in the German-speaking literature. Whereas the former used a chiefly macroscopic approach to an academic classification, the concepts of the latter were based on microscopic observations. In contrast to pathologists, who in the nineteenth century were dominated by Virchow and his teachings, dermatologists as well as microscopically active gynecologists already applied histological findings for diagnostics and subsequent therapy. Chapters dealing with diseases of the skin in multivolume handbooks of pathology were initially mainly written by dermatologists. The majority of textbooks of dermatopathology were also written by dermatologists. One of the current aims of pathologists is the application of additional methods, e.g. molecular pathology in order to better understand and treat neoplastic diseases, in particular pigmented skin tumors.

Smaller panel, similar results: genomic profiling and molecularly informed therapy in pancreatic cancer.

BACKGROUND: Pancreatic cancer has a dismal prognosis. One reason is resistance to cytotoxic drugs. Molecularly matched therapies might overcome this resistance but the best approach to identify those patients who may benefit is unknown. Therefore, we sought to evaluate a molecularly guided treatment approach. MATERIALS AND METHODS: We retrospectively analyzed the clinical outcome and mutational status of patients with pancreatic cancer who received molecular profiling at the West German Cancer Center Essen from 2016 to 2021. We carried out a 47-gene DNA next-generation sequencing (NGS) panel. Furthermore, we assessed microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status and, sequentially and only in case of KRAS wild-type, gene fusions via RNA-based NGS. Patient data and treatment were retrieved from the electronic medical records. RESULTS: Of 190 included patients, 171 had pancreatic ductal adenocarcinoma (90%). One hundred and three patients had stage IV pancreatic cancer at diagnosis (54%). MMR analysis in 94 patients (94/190, 49.5%) identified 3 patients with dMMR (3/94, 3.2%). Notably, we identified 32 patients with KRAS wild-type status (16.8%). To identify driver alterations in these patients, we conducted an RNA-based fusion assay on 13 assessable samples and identified 5 potentially actionable fusions (5/13, 38.5%). Overall, we identified 34 patients with potentially actionable alterations (34/190, 17.9%). Of these 34 patients, 10 patients (10/34, 29.4%) finally received at least one molecularly targeted treatment and 4 patients had an exceptional response (>9 months on treatment). CONCLUSIONS: Here, we show that a small-sized gene panel can suffice to identify relevant therapeutic options for pancreatic cancer patients. Informally comparing with previous large-scale studies, this approach yields a similar detection rate of actionable targets. We propose molecular sequencing of pancreatic cancer as standard of care to identify KRAS wild-type and rare molecular subsets for targeted treatment strategies.

Methanogenesis produces strong 13C enrichment in stromatolites of Lagoa Salgada, Brazil: a modern analogue for Palaeo-/Neoproterozoic stromatolites?

Holocene stromatolites characterized by unusually positive inorganic δ(13) CPDB values (i.e. up to +16‰) are present in Lagoa Salgada, a seasonally brackish to hypersaline lagoon near Rio de Janeiro (Brazil). Such positive values cannot be explained by phototrophic fixation of CO2 alone, and they suggest that methanogenesis was a dominating process during the growth of the stromatolites. Indeed, up to 5 mm methane was measured in the porewater. The archaeal membrane lipid archaeol showing δ(13) C values between -15 and 0‰ suggests that archaea are present and producing methane in the modern lagoon sediment. Moreover, (13) C-depleted hopanoids diplopterol and 3ß-methylated C32 17ß(H),21ß(H)-hopanoic acid (both -40‰) are preserved in lagoon sediments and are most likely derived from aerobic methanotrophic bacteria thriving in the methane-enriched water column. Loss of isotopically light methane through the water column would explain the residual (13) C-enriched pool of dissolved inorganic carbon from where the carbonate constituting the stromatolites precipitated. The predominance of methanogenic archaea in the lagoon is most likely a result of sulphate limitation, suppressing the activity of sulphate-reducing bacteria under brackish conditions in a seasonally humid tropical environment. Indeed, sulphate-reduction activity is very low in the modern sediments. In absence of an efficient carbonate-inducing metabolic process, we propose that stromatolite formation in Lagoa Salgada was abiotically induced, while the (13) C-enriched organic and inorganic carbon pools are due to methanogenesis. Unusually, (13) C-enriched stromatolitic deposits also appear in the geological record of prolonged periods in the Palaeo- and Neoproterozoic. Lagoa Salgada represents a possible modern analogue to conditions that may have been widespread in the Proterozoic, at times when low sulphate concentrations in sea water allowed methanogens to prevail over sulphate-reducing bacteria.

Cytoskeletal heterogeneity of an epithelioid sarcoma with expression of vimentin, cytokeratins, and neurofilaments.

We studied an unusual sarcoma with morphologic features diagnostic of epithelioid sarcoma by conventional light microscopy, transmission electron microscopy, and immunohistochemistry. The primary tumor, which was located in the deep soft tissues of the buttock of a 32-year-old woman, and its metastases to lymph nodes, liver, and lung were available for investigation. The histomorphological and ultrastructural appearance of the primary tumor and its metastatic deposits were typical of epithelioid sarcoma. Immunohistochemistry revealed a strong and uniform reactivity for vimentin in both the primary tumor and its metastases. In contrast, a marked cytoskeletal heterogeneity became evident for cytokeratins and neurofilaments, which were observed exclusively in lymph node metastasis. To our knowledge, the observation of neurofilaments in epithelioid sarcoma has not previously been reported.

Chordoma with a predominant retrosacral tumor mass.

Chordomas are malignant tumors with lobulated structure which usually consists of vacuolated physaliferous cells in a mucoid stroma (Enzinger et al. 1969). These cells originate from remnants of the chorda dorsalis. Most chordomas are located either at the end of the vertebral column, i.e., in the sacrococcygeal region or at the base of the skull near the sphenooccipital synchondrosis. More than half of all tumors are located in the sacrococcygeal region. In contrast to most cases of sacrococcygeal chordomas which show a predominant presacral tumor infiltration we report on a patient suffering from a sacrococcygeal chordoma with a retrosacral tumor mass. Here, the presacral tumor infiltration became apparent only much latter. It was nevertheless of great prognostic relevance as tumor infiltration of the urinary bladder lead to lethal septicaemia.

Structural aberrations of chromosome 6 in three uterine smooth muscle tumors.

Clonal karyotypic alterations of chromosome 6 in three uterine smooth muscle tumors are reported. In all cases an apparently identical breakpoint on the short arm of chromosome 6 was found. Two cases displayed the histologic features of cell-rich myomas with severe nuclear atypia but no clear evidence for malignancy. The remaining case was a primary uterine leiomyosarcoma of an 80-year-old patient showing an apparently balanced reciprocal chromosomal translocation, t(1;6)(p32-33;p21.3), as the sole karyotypic abnormality. This type of aberration has not been reported before in leiomyosarcomas. Because of the nuclear atypia in the other myomas with a breakpoint involving the short arm of chromosome 6 we feel that this cytogenetically recognizable but rare subgroup of uterine smooth muscle tumors warrants a careful clinical follow-up.

Malignant fibrous histiocytoma: histomorphological pattern or tumor type.

During the past years MFH has obviously been used as a diagnostic waste basket for hard to classify tumours of all kinds. Immunohistochemistry revealed insights into cellular differentiation of neoplastic proliferations, also raising new questions because of unexpected antigen expression, as, for instance, cytokeratins in MFH. Thus, a number of tumours originally diagnosed as MFH could be reclassified, i.e., as leiomyosarcoma, melanoma or anaplastic carcinoma. Nevertheless, there remain a certain number of sarcomas which lack any evidence of special cellular differentiation. These proliferations of primitive mesenchymal or fibroblastic cells, often with a typical histological, storiform pattern, qualify as MFH. Using these strict criteria, the diagnosis of MFH will become rarer, though not obsolete (like hemaugioperizytoma years ago!).

Malignant fibrous histiocytoma. History, histology, histogenesis.

At the XVI. International Congress of the International Academy of Pathology (Vienna, 1986), a session was dedicated to the classification of soft tissue tumors. At this occasion a critical review of malignant fibrous histiocytoma (MFH) was presented. A) The history of MFH revealed that this tumor had been known for many years under a variety of names. Moreover, MFH apparently had frequently been misinterpreted as other tumor types, as for instance rhabdomyosarcoma. Today, there is a discrepancy between the high incidence of MFH among soft tissue sarcomas and its underrepresentation in some widely used tumor classifications. B) The histological appearance may be fully developed and typical for MFH. However, it also may be merely compatible with MFH in less typical tumor areas. Regional differences in morphological appearance may be pronounced. Differential diagnosis can be helped by histochemical methods. C) Histochemical methods--among others--also help to shed light on the histogenesis. More recent findings point to MFH, as a tumor of fibroblasts rather than histiocytes with similarities to loose areolar connective tissue. Although MFH-like areas may occur focally within a variety of different tumors, there remains a large group of sarcomas which do not display any signs of further differentiation even after careful work-up. In these cases the application of the term MFH, as it is understood today, appears to be justified.

Fibrous histiocytoma: a histological and statistical analysis of 155 cases.

Various salient histological features were rated from + to +++ in a semiquantitative evaluation of a series of 155 cases of fibrous histiocytoma. Relations between individual histological features, as well as between histological findings, localisation and size of lesions, and age or sex of the patient were tested statistically. Most impressive was an inverse proportional relationship between cellular and fibrillar densities: highly cellular fibrous histiocytomas chiefly showed little fiber formation. Accordingly, cases with marked fiber formation were distinguished by low cellularity. Based on this statistically significant relation, 3 subtypes could be classified on a scale of increasing fiber formation and decreasing cellular density. The majority of cases showed medium cellularity and fibrillar density, with distinct storiform (spokewheel or "whirlygig") pattern which is compatible with typical storiform histocytoma, including clincally progressive, recurrant FH and/or "dermatofibrosarcoma protuberans". The typical patient was more frequently female than male, 40 years of age with a 0.5 to 1.0 cm size tumor node in the lower extremities located in the corium, often with beginning infiltration of the subcutaneous fat tissue.

Malignant tumor of humerus with features of "adamantinoma" and Ewing's sarcoma.

This female patient was born in 1935 and died in 1976 with a malignant bone tumor involving the proximal humerus following multiple local recurrences, axillary lymph node metastases, and pulmonary metastases. Histologically, over the course of time, there was an increase in features of an atypical Ewing's sarcoma, at the expense of findings of a typical, extra-cranial so-called adamantinoma. In contrast to another report, our case showed neither epithelial nor endothelial features on fine structural examination, but rather primitive mesenchymal cells, as is described for Ewing's sarcomas.

Postirradiation osteosarcoma of pelvic bone with unusual histological pattern.

This paper reports an osteosarcoma of the pelvic bone appearing 8 years after postoperative radiation therapy for carcinoma of the uterus and ovary. Unusual was the existence of well differentiated parts and possibly early sarcomatous changes which were found only in the primary tumour and not in the metastases.

Pulmonary myofibroblastic nodules with "amianthoid features".

Two consecutive publications appeared 1989 in the same number of a medical journal, which reported peculiar spindle-cell tumors with dense collagen or hyaline nodules, exclusively in inguinal lymph nodes of adults. The first series of 22 cases bore the title "Palisaded myofibroblastoma, a benign mesenchymal tumor of lymph node", the second with 6 identical cases "Intranodal hemorrhagic spindle-cell tumor with "amianthoid" fibers". The following case report deals with a similar tumorous lesion, with multiple small pulmonary nodules, without recognizable lymph node constituents.