Petr Mukensnabl

Mucinous Carcinoma of the Skin, Primary, and Secondary A Clinicopathologic Study of 63 Cases With Emphasis on the Morphologic Spectrum of Primary Cutaneous Forms: Homologies With Mucinous Lesions in the Breast

We present the largest series of mucinous carcinoma involving the skin, describing the histopathologic, immunohistochemical, electron microscopic, and cytogenetic findings. Our aim was fully to characterize the clinicopathologic spectrum and compare it with that seen in the breast. In addition, we wished to reevaluate the differential diagnostic criteria for distinguishing primary mucinous carcinomas from histologically similar neoplasms involving the skin secondarily, and study some aspects of their pathogenesis. We demonstrate that primary cutaneous mucinous carcinomas span a morphologic spectrum compatible to their mammary counterparts. Both pure and mixed types can be delineated morphologically, and some lesions have mucocele-like configurations. Most lesions seem to originate from in situ lesions that may represent, using mammary pathology terminology, ductal hyperplasia, atypical ductal hyperplasia, or ductal carcinoma in situ or a combination of the three. Inverse cell polarity appears to facilitate the progression of the changes similar to lesions in the breast. The presence of an in situ component defines the neoplasm as primary cutaneous, but its absence does not exclude the diagnosis; although for such neoplasms, full clinical assessment is essential. Mammary mucinous carcinoma involving the skin: all patients presented with lesions on chest wall, breast, axilla, and these locations can serve as clue to the breast origin. Microscopically, cutaneous lesions were of both pure and mixed type, and this correlated with the primary in the breast. Dirty necrosis was a constant histologic finding in intestine mucinous carcinomas involving the skin, and this feature may serve as a clue to an intestinal origin.

Morphologic diversity of malignant neoplasms arising in preexisting spiradenoma, cylindroma, and spiradenocylindroma based on the study of 24 cases, sporadic or occurring in the setting of Brooke-Spiegler syndrome.

The authors present a series of 24 malignant neoplasms arising in preexisting benign spiradenoma (20), cylindroma (2), and spiradenocylindroma (2). Nineteen patients (12 females, 7 males; age range, 41 to 92 y) had a solitary neoplasm (size range, 2.2 to 17.5 cm; median 4 cm), whereas the remaining 5 (4 females, 1 male; age range, 66 to 72 y) manifested clinical features of Brooke-Spiegler syndrome (BSS), an autosomal dominantly inherited disease characterized by widespread, small, benign neoplasms on which background larger malignant lesions appeared. Microscopically, all cases showed the residuum of a preexisting benign neoplasm. The malignant components of the lesions were variable and could be classified into 4 main patterns, occurring alone or in combination: 1) salivary gland type basal cell adenocarcinoma-like pattern, low-grade (BCAC-LG); 2) salivary gland type basal cell adenocarcinoma-like pattern, high-grade (BCAC-HG); 3) invasive adenocarcinoma, not otherwise specified (IAC-NOS); and 4) sarcomatoid (metaplastic) carcinoma. In 1 case of IAC-NOS, an in situ adenocarcinoma was also found, presumed to have evolved from an adjacent adenomatous and atypical adenomatous component. Cases harboring a sarcomatoid carcinoma featured a malignant epithelial component composed of varying combinations of BCAC-HG, BCAC-LG, IAC-NOS, or squamous cell carcinoma, whereas the sarcomatoid component appeared as either a pleomorphic or spindle-cell sarcoma. Additionally, in 2 cases there were foci of heterologous chondrosarcomatous differentiation and in 1 case there was rhabomyosarcomatous differentiation. Of the 21 patients with available follow-up (range, 3 mo-15 y; average 4.8 y; median 3.5 y), 10 were without evidence of disease, 1 was alive with metastatic disease, 1 was alive with BSS, 3 developed local recurrences, 4 had died of disease, and 2 were dead of other causes. The histologic pattern of the malignant neoplasm correlated to some extent with the clinical course. BCAC-LG neoplasms showed a less aggressive course, with local recurrences but no distant metastases, whereas the BCAC-HG neoplasms typically followed a highly aggressive course resulting in the death 3 of 6 patients with BCAC-HG. Patients with sarcomatoid carcinoma had a relatively good survival. Molecular genetic investigations revealed no mutations in the CYLD gene in the 4 sporadic cases investigated. One patient with BSS revealed a novel missense germline mutation in exon 14 (c. 1961T>A, p. V654E), whereas a living descendant of another deceased patient demonstrated a recurrent nonsense germline mutation in exon 20 (c. 2806C>T, p. R936X). Given the morphologic diversity and complexity of the neoplasms in question, we propose using a more specific terminology with the precise description of the neoplasm components, rather than generic and less informative terms such as “spiradenocarcinoma” or “carcinoma ex cylindroma.”

Brooke-Spiegler syndrome: report of a case with combined lesions containing cylindromatous, spiradenomatous, trichoblastomatous, and sebaceous differentiation.

Brooke-Spiegler syndrome is an autosomal dominantly inherited disease with predisposition to cutaneous adnexal neoplasms, most commonly cylindromas and trichoepitheliomas. We report a patient in whom 11 lesions were removed from the scalp and face for various reasons over a period of 3 years. The histopathological survey revealed a plethora of benign adnexal neoplasms showing apocrine, follicular, and sebaceous differentiation occurring independently and conjointly. The histopathological spectrum in our patient included cylindromas, spiradenomas, trichoepitheliomas, small nodular trichoblastomas, and lymphadenomas. Many lesions had hybrid features of two or more neoplasms. By far the most common composite tumor was spiradenocylindroma. Some spiradenocylindromas demonstrated prominent sebaceous or trichoblastomatous differentiation or both. We suggest the terms “sebaceous spiradenocylindroma” and “trichospiradenocylindroma” for these lesions. The occurrence of sebaceous and trichoblastic differentiation in spiradenocylindromas is a further proof that spiradenoma and cylindroma are not eccrine tumors but neoplasms of the folliculosebaceousapocrine unit.

Cribriform adenocarcinoma of the tongue: a hitherto unrecognized type of adenocarcinoma characteristically occurring in the tongue.

We report a review of our institutional and consultation files in order to select cases of hitherto unrecognized type of adenocarcinoma occurring in the tongue.

Spiradenocylindromas of the skin: Tumors with morphological features of spiradenoma and cylindroma in the same lesion: Report of 12 cases

Twelve cases of spiradenocylindromas, which revealed features of both spiradenoma and cylindroma in the same tumor mass, are presented. Nine female patients had multiple neoplasms occurring mostly on the scalp, and two female and one male patient had a solitary cutaneous lesion. Three of the female patients with multiple cutaneous tumors had a familial history of similar cutaneous neoplasms. In one of the patient’s family, the multiple cutaneous tumors were known to occur in multiple family members in four consecutive generations. One patient with multiple cutaneous lesions was known to have associated multiple kidney cysts as confirmed by computed tomography. Histologically, spiradenocylindromas are composed of intermixed areas that are either of typical spiradenoma in appearance or of typical cylindroma appearance. Apocrine and trichoepitheliomatous differentiation seen in two cases in the present series points to spiradenomas, as well as cylindromas, having complex hair follicle (folliculo‐ sebaceous apocrine) rather than eccrine differentiation. The presence of lymphoid tissue was a histological feature in the present series, which was prominent in all the spiradenomatous parts of the tumors and which was scanty or practically absent in all the cylindromatous parts. The selective presence of lymphocytes in spiradenoma and an absence in cylindroma suggest that spiradenomas have the unique property of attracting lymphocytes. The malignant tumors arising in three patients in the present series had the morphology of a poorly differentiated epithelioid neoplasm. Three patients died of the disease and the other patients were either free of disease or alive with disease 1–30 years on follow up.

Gastrointestinal stromal tumor of the pancreas: case report with documentation of KIT gene mutation

Sir, mesenchymal tumors of the pancreas are exceedingly rare, accounting for less than 1% of all pancreatic tumors, and most of them have been reported in small series or as single case reports. This group of pancreatic tumors includes leiomyosarcoma, malignant peripheral nerve sheath tumor, malignant fibrous histiocytoma, liposarcoma, rhabdomyosarcoma,hemangiopericytoma,schwannomaandsolitary fibrous tumor. In the gut, mesenchymal tumors are more common, and the majority of these are formed by gastrointestinal stromal tumors (GISTs). GISTs are defined as KIT-positive mesenchymal spindle cell or epithelioid neoplasms showing differentiation toward the interstitial cell of Cajal. GISTs occur most commonly in the stomach (60–70%), small intestine (20–25%), colorectum (5%) and esophagus (<5%). They were also occasionally reported in extragastrointestinal sites,suchasurinarybladder,gallbladder,omentumandmesentery[1].WereportacaseofaGIST of the pancreatic head in a 70-year-old woman exhibiting all diagnostic histopathological, immunohistochemical and molecular genetic features, which has not yet been properly documented in this location. Although Neto et al. publishedacaseofpancreatic GISTrecently,evaluationofc-kit mutations as well as computed tomography (CT) scan or microphotograph documenting pancreatic location of the tumor is missing in their report [7].

Cribriform adenocarcinoma of minor salivary gland origin principally affecting the tongue: characterization of new entity.

We present a series of 23 cases of a distinctive, hitherto poorly recognized low-grade adenocarcinoma, with several histologic features reminiscent of papillary carcinoma of the thyroid, and which mostly but not exclusively occurs in the tongue. All the tumors were unencapsulated and were divided into lobules that were composed mainly of cribriform and solid growth patterns. Therefore, we propose the name “cribriform adenocarcinoma of minor salivary gland origin (CAMSG).” All the patients were adults with a mean age at diagnosis of 55.8 years (range, 25 to 85 y). Fourteen of the 23 tumors were localized in the tongue, 3 in the soft palate, 2 in the retromolar buccal mucosa, 3 in the lingual tonsils, and 1 in the upper lip. Fifteen patients of 23 had synchronous metastases in the cervical lymph nodes at the time of diagnosis, bilateral in 3 cases. In 3 patients, the nodal metastasis was the first evidence of disease, later investigation revealing primary neoplasms in the base of tongue and tonsil, respectively. In addition, 1 patient developed a cervical lymph node metastasis 8 years after excision of a primary tumor of the tongue. Data on treatment and follow-up were available in 14 cases. The patients were treated by radical excision with clear margins (12 cases) or by simple excision (2 cases). Neck dissection was performed in 10 patients; 9 received radiotherapy, but none were treated by chemotherapy. Clinical follow-up ranged from 2 months to 13 years (mean, 6 y and 5 mo). Twelve patients are alive with no evidence of recurrent or metastatic disease after treatment, 1 patient died 2 years after surgery without evidence of tumor, and 1 patient is alive with recurrent tumor of the palate.

Cutaneous lymphoid hyperplasia and other lymphoid infiltrates of the breast nipple: a retrospective clinicopathologic study of fifty-six patients.

This study characterizes the clinicopathological spectrum of lymphoproliferations involving the breast nipple and/or areola. Morphologic, immunohistochemical, molecular-genetic, and clinical features of 58 specimens from 56 patients were analyzed. They were re-diagnosed as cutaneous lymphoid hyperplasia (CLH, n = 44); other benign lymphoid infiltrates (OBLI, n = 8); peripheral T-cell lymphoma, not otherwise specified (n = 1); cases with overlapping features of CLH and B-cell lymphoma (n = 3), one of them composed of spindle cells. Cutaneous lymphoid hyperplasia infiltrates were dense, composed mainly of B cells forming follicles with germinal centers (GC). Cutaneous lymphoid hyperplasia frequently showed features suggesting a malignancy as coalescing follicles with non-polarized germinal centers lacking mantle zones, and smudged infiltrates of lymphoid cells spreading into collagen (often as “Indian files”), smooth muscle, vessel walls, and nerve sheaths. Only two cutaneous lymphoid hyperplasias recurred; otherwise all patients are without disease (mean follow-up 62 months). Monoclonal rearrangement of immunoglobulin heavy chain gene was detected in five, and of T-cell receptor γ gene in two cutaneous lymphoid hyperplasias using polymerase chain reaction (PCR), but the patients fared well too. In 47% of cases Borrelia burgdorferi was detected by polymerase chain reaction and/or serology, of which one was monoclonal. We conclude that cutaneous lymphoid hyperplasia is the most common lymphoproliferation of the breast nipple, rarely recognized clinically, and often overdiagnosed histologically as lymphoma.

Carcinoid-like pattern in sebaceous neoplasms: another distinctive, previously unrecognized pattern in extraocular sebaceous carcinoma and sebaceoma.

This report emphasizes a carcinoid-like pattern, a previously unrecognized feature in cutaneous sebaceous neoplasms. We report 7 patients with sebaceous tumors in which neoplastic cells were arranged in a trabecular and ribbon-like pattern or formed rosettes/pseudorosettes. The cases included 6 men and 1 woman, with their ages at the diagnosis ranging from 43 to 87 years (median age, 59). All patients presented with a solitary lesion. Locations were the scalp (n = 6) and forearm (n = 1). The carcinoid-like arrangement of neoplastic cells was the sole pattern in 4 cases, and in 3 cases the so-called labyrinthine/sinusoidal and/or rippled patterns were seen in addition. Sebaceous differentiation in the form of mature sebocytes varied from almost none to approximately 10%. Although the neoplasm appeared benign architecturally, the presence of cytologic atypia qualified 2 tumors as low-grade carcinomas. Four lesions represented sebaceomas, and in 1 case microscopic delineation between a carcinoma and sebaceoma was difficult. No neuroendocrine differentiation was demonstrated immunohistochemically, histochemically, and ultrastructurally. Electron microscopic examination performed in 1 case of carcinoma revealed lipid vacuoles in a minority of cells. There were no membrane-bound neuroendocrine granules. Rare cells contained peculiar large helioid inclusions. We conclude that the carcinoid-like pattern is another distinctive pattern indicative of sebaceous neoplasms. This pattern seems to be closely related to the rippled and labyrinthine/sinusoidal patterns, as exemplified by our cases, in which these arrangements sometimes occurred simultaneously.

Sebaceous carcinoma arising in nevus sebaceus of Jadassohn: a clinicopathological study of five cases.

The authors report a small series of sebaceous carcinoma developing in nevus sebaceus of Jadassohn (also known as organoid nevus) and analyze similar cases reported in the literature. All of our patients were females (age range 57-71 years; median 60 years) who had the organoid nevus on the scalp, face, or nuchal area, the rest of which was recognized clinically and/or histologically. All sebaceous carcinomas manifested unquestionable architectural (asymmetry, invasive growth) and cytological features of a carcinoma (cellular and nuclear pleomorphism, plentiful atypical mitoses, necroses en masse), demonstrated unambiguous sebaceous differentiation in the form of mature sebocytes, and lacked other differentiations. The sebaceous carcinoma was always accompanied by other benign or malignant adnexal lesions such as sebaceoma, syringocystadenoma papilliferum, syringocystadenocarcinoma papilliferum, trichoblastoma, tricholemmoma, desmoplastic tricholemmoma, or syringoma. In three cases, prominent mucinous metaplasia of sweat ducts and glands was seen. In two of these cases, sweat ducts exhibited hyperplastic changes. The analysis of the previously published material and our cases indicates that sebaceous carcinoma arising in organoid nevus has a female predilection and tends to occur in elderly patients. It may involve any site where nevus sebaceus typically occurs. Clinically, the tumor presents as a solitary nodule, ulcerated tumor, or mass, often with a recent history of rapid growth. It may arise alone, but it occurs more frequently as part of multiple benign and malignant adnexal tumors. The lesion does not seem to be associated with Muir-Torre syndrome. The rest of organoid nevus is usually recognized both clinically and microscopically, although large tumors may overgrow and mask the nevus. The tumor seems to be a low-grade carcinoma in terms of clinical behavior.