Primary cutaneous CD30+ anaplastic large-cell lymphoma with generalized skin involvement and involvement of one peripheral lymph node, successfully treated with low-dose oral etoposide

Primary cutaneous CD30+ anaplastic large-cell lymphoma (PCALCL) in adults is rare, and the prognosis is generally excellent. Multifocal PCALCL tends to relapse after multiagent chemotherapy and is generally considered more prone to progress to extracutaneous involvement than is the localized disease. We report a 43-year-old woman with PCALCL who had generalized skin involvement accompanied by involvement of one peripheral draining lymph-node region. Although the disease relapsed after multiagent chemotherapy regimens, the disease was successfully treated with low-dose etoposide. We reviewed the previously reported cases of PCALCL treated with low-dose etoposide. We suggest that oral etoposide might be a useful effective treatment for treatment of relapsed multifocal PCALCL.     

Primary cutaneous anaplastic CD30+ large cell lymphoma

Primary cutaneous anaplastic CD30+ large cell lymphoma (PCALCL) is part of the spectrum of primary cutaneous CD30+ lymphoproliferative disorders together with lymphomatoid papulosis. It affects mainly elderly patients and presents as skin nodules that tend to ulcerate. Histological and immunohistochemical study show the expression of CD30 antigen in more than 75 % of neoplastic cells. Currently it is considered a low grade lymphoma with favourable prognosis and good response to treatments such as local radiotherapy, methotrexate or surgery. We report a 93-year-old patient with ulcerated nodules in her right leg. Histological and immunohistochemical study confirmed the diagnosis of PCALCL, of non-B, non-T origin. The patient was treated with local radiotherapy with progressive resolution of skin nodules and absence of relapse at 6 months follow-up.     

Primary cutaneous CD30+ anaplastic large cell lymphoma treated with radiotherapy and methotrexate with development of xanthomas at the sites of prior disease

Primary cutaneous anaplastic large cell lymphoma is a rare type of cutaneous T‐cell lymphoma, and the involvement of the ocular adnexa is extremely rare. Secondary xanthoma‐like changes after radiation therapy or chemotherapy have been rarely reported in association with large‐cell T‐cell anaplastic lymphoma. We report one case of a primary C‐anaplastic large cell lymphoma affecting the eyelid with fast progression with multiple nodules in various anatomic sites and development of xanthoma‐like lesions after treatment.     

Progress of multiple cutaneous and subcutaneous melanoma metastases of the face during imiquimod treatment

A 68‐year‐old man developed a local recurrence with multiple cutaneous and subcutaneous nodules three months after excision of a primary malignant melanoma of the temple. Despite extensive surgery and adjuvant irradiation, another local recurrence occurred. Following further local progression during dacarbazine chemotherapy, topical treatment with imiquimod was begun and the chemotherapy was changed to fotemustine. During this treatment further local progression occurred and two months later regional lymph node and distant metastasis were detected. The patient died from his tumor disease eighteen months after the first diagnosis of malignant melanoma.     

Cutaneous gamma‐delta T‐cell lymphoma with central nervous system involvement: report of a rarity with review of literature

Primary cutaneous gamma‐delta (γδ) T‐cell lymphoma is an extremely rare and aggressive variant of cutaneous lymphoma. Central nervous system (CNS) involvement, a rare finding, and hemophagocytic syndrome are two complications that are commonly fatal. We describe a 58‐year‐old patient presenting with skin plaque who subsequently developed subcutaneous nodules diagnosed as cutaneous T‐cell lymphoma (CTCL), clinically resembling ‘mycosis fungoides’. The patient was treated with repeat topical radiation therapies but had frequent relapsed disease. Approximately 4.5 years after, the patient presented with third and sixth cranial nerve palsies and was found to have CNS involvement by lymphoma per positron emission tomography—computed tomography (PET/CT) and a biopsy of foramen magnum. Phenotypically, the tumor cells were CD3(+)/CD4(?)/CD8(?)/CD7(+)/CD5(?)/CD30(?)/TCRαβ(?)/TCRγδ(+). Despite aggressive strategies taken, the patient expired 3 months after the diagnosis of the CNS lesion. A retrospective investigation proved the original CTCL to be γδ T‐cell in origin, confirming an indolent cutaneous γδ T‐cell lymphoma with eventual CNS manifestation. We present this case to draw attention to the entity, which can occasionally present with misleading histopathologic and clinical features. In addition, we provide a review of the literature to summarize clinical and pathologic features of the reported similar cases.     

Scalp tumour as a sign of systemic B-cell lymphoma

An 86-year-old man presented with a painful reddish tumour on the scalp with a 3-month history, mental confusion with recent onset and lymphadenopathies. Histological examination of the lymph node and cutaneous lesion revealed a dense infiltrate of atypical and large B cells. There was no evidence of bone marrow invasion. According to REAL (Revised European-American Classification of Lymphoid Neoplasms), this lymphoma was considered as a diffuse large B-cell lymphoma with concurrent cutaneous and nodal involvement. Cerebral computerized tomography (CT) scan showed bone and dura mater invasion in the right parieto-occipital region with collapse of lateral ventricle. The patient was submitted to systemic chemotherapy with cyclophosphamide, vincristine and prednisolone (CVP). There was a good response with regression of the cutaneous lesion, but the patient died after the third cycle. We point out the unusual clinical presentation and aggressive behaviour of this lymphoma.     

Diffuse (anergic) cutaneous leishmaniasis responding to amphotericin B

American cutaneous leishmaniasis is an important endemic zoonotic disease in the New World that comprises a spectrum of clinical manifestations. Diffuse cutaneous leishmaniasis (DCL) is a rare form of the disease characterized by antigen‐specific immunodeficiency that often presents with multiple disfiguring non‐ulcerated confluent nodules or plaques that involve large areas of the skin, resembling lepromatous leprosy. Relapse is invariable in advanced stages, despite aggressive chemotherapy, and a plethora of drugs has been tested with unchanging results. We report on a severe an exceptional case that resolved after treatment with amphotericin B, a drug considered only mildly effective, and discuss the therapeutic approach to this disease.     

CD30+ cutaneous lymphoproliferative disorders: the Stanford experience in lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma

BACKGROUND: CD30+ cutaneous lymphoproliferative disorders (CLPDs) include lymphomatoid papulosis, borderline cases of CD30+CLPDs, and primary cutaneous anaplastic large cell lymphoma (PCALCL). Prior studies have shown CD30+CLPDs have an excellent prognosis. OBJECTIVE: We sought to present the single-center experience of Stanford University, Stanford, Calif, in the management of CD30+CLPDs. METHODS: A retrospective cohort analysis of 56 patients with CD30+CLPDs treated at our institution was performed. RESULTS: No patients with lymphomatoid papulosis died of disease, and overall survival was 92% at 5 and 10 years. Disease-specific survivals at 5 and 10 years for PCALCL were 85%. Disease-specific survival at 5 years for localized versus generalized PCALCL was 91% versus 50% (P =.31). PCALCL was highly responsive to treatment, but the relapse rate was 42%. In all, 3 patients progressed to extracutaneous stage of disease. No clinical or histologic factors analyzed were predictive of worse outcome in lymphomatoid papulosis and PCALCL. CONCLUSION: Similar to prior reports from multicenter European groups, the single-center experience at our institution demonstrates CD30+CLPDs have an overall excellent prognosis; however, cases of PCALCL with poor outcome do exist.     

Cutaneous Hodgkin's disease

Cutaneous Hodgkin's disease is a rare condition that usually occurs late in the course of Hodgkin's lymphoma. This rare condition is thought to have decreased in incidence in recent decades, likely owing to improved treatment of patients with Hodgkin's disease, who are receiving improved chemotherapy and radiation therapy, and the advent of peripheral blood stem cell transplantation. We present the case of a man who developed specific cutaneous Hodgkin's lymphoma 6 months after nonmyeloablative allogenic stem cell transplantation for his recurrent systemic disease. The patient's manifestation of relapse was cutaneous dissemination of the tumor, manifested by erythematous papules and ulcerated nodules. At the time of the cutaneous relapse he had minimal systemic disease. This case illustrates an example of this complication of Hodgkin's disease and stresses the importance of a timely diagnosis to direct appropriate therapy. A review of the literature demonstrates that the patient's lesion morphology and distribution are typical of specific manifestations of cutaneous Hodgkin's disease.     

Skin metastasis of head and neck carcinoma predictive for dismal outcome

A 64-year-old female with locally advanced oropharyngeal carcinoma presented with an innocuous appearing macule on the abdomen. The lesion rapidly enlarged over 2 weeks into an inflammatory 5 cm fleshy nodule that was diagnosed as squamous cell carcinoma (SCC) and was found to overexpress epidermal growth factor receptor (EGFR). A fatal outcome occurred 3 months after the initial diagnosis of cancer, in spite of chemotherapy and treatment with EGFR inhibitors (cetuximab). Cutaneous metastases occur in 10 percent of squamous cell carcinomas of the head and neck. Contiguous cutaneous metastases in the head and neck areas are by far the most common. Conversely, isolated infradiaphragmatic cutaneous metastases are exceedingly rare and are associated with an aggressive clinical course. In a patient with cancer, the possibility of distant skin metastasis should be considered whenever new cutaneous nodules appear.     

Case of low‐grade neuroendocrine carcinoma of the skin presenting metastases to lymph nodes and peritoneum

A 61‐year‐old Japanese man had a gradually growing, red‐colored nodule in his umbilicus from 3 years ago. He had no symptoms such as hot flush, diarrhea or wheezing. Computed tomography detected a 3.0 cm × 3.0 cm enhanced nodule on the umbilical portion, inguinal and axillary lymph node swelling, and peritoneal nodules. Upper and lower gastrointestinal endoscopy and cystoscopy did not show any other tumor. We resected the umbilical nodule and subjected the inguinal lymph node and peritoneal nodule to biopsy. Histopathological findings indicated that the cutaneous lesion was composed of variously sized nests that included small, monomorphic, round to polygonal cells, mainly in the dermis to the peritoneum. Mitotic figures were scant. The inguinal lymph node and peritoneal nodule were positive for metastasis. Immunohistochemistry was diffusely positive for cytokeratin (CK)‐7, CD56, chromogranin A, synaptophysin, estrogen receptor‐α, progesterone receptor, GATA3 and carcinoembryonic antigen, and focally positive for mammaglobin and gross cystic disease fluid protein 15. The Ki‐67 labeling index was 1.5%. The patient was diagnosed with a case of low‐grade neuroendocrine carcinoma of the skin (LGNECS) occurring on the umbilicus. This case exhibited distant peritoneal metastasis, as well as inguinal and axillary lymph node metastases; however, the patient is alive without chemotherapy at 23 months after the first visit. LGNECS is a newly proposed, extremely rare entity that has been reported under various names, including primary cutaneous carcinoid tumor. In the present case, this tumor shows a slow‐growing nature and favorable prognosis, even though it harbors metastatic potential.     

Disseminated coccidioidomycosis

We report a case of disseminated coccidioidomycosis in a 39-year-old Japanese male whose illness developed after returning from a trip to an endemic area. He showed positive coccidioidin skin reaction throughout the entire course of his illness. The primary lesion in the lung subsequently spread to the bone. While the patient was on treatment with 5-FC, he made another trip to the same endemic area. After this episode, he developed pulmonary symptoms and cutaneous nodules on his wrist. The possibility of reinfection with Coccidioides immitis is discussed. Electron microscopy of the cutaneous nodules revealed that the spherules examined maintained their structural integrity in the granulomatous lesion, suggesting the high viability of the organism. Host-parasitic interaction in coccidioidomycosis is discussed.     

Primary cutaneous histiocyte and neutrophil-rich CD30+ and CD56+ anaplastic large-cell lymphoma with prominent angioinvasion and nerve involvement in the forehead and scalp of an immunocompetent woman

BACKGROUND: Cutaneous lymphomas co-expressing CD56 and CD30 are very rare. They share a clinicopathological overlap with natural killer- (NK)/T-cell lymphomas and anaplastic large-cell lymphomas (ALCLs), two entities with widely disparate clinical behavior. METHODS: We present a case of an immunocompetent 57-year-old Caucasian woman with a rapidly growing, angiodestructive and neuroinvasive primary cutaneous ALCL (PCALCL). The neoplastic population of large anaplastic CD30+ and CD56+ T cells was masked by a massive admixture of histiocytes and neutrophils. The partially ulcerated and pus-secreting tumor involved the forehead and scalp and was assessed as clinical stage IAE. RESULTS: After chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), the patient achieved a complete remission. Additionally, high-dose chemotherapy with autologous peripheral blood stem-cell transplantation was administered as a consolidation of complete remission, in which she has remained for 6 years. CONCLUSIONS: This is the first CD30+ and CD56+ primary skin lymphoma to be reported on the head. The presented case carries a remarkable combination of clinicopathological features of PCALCL and NK-/T-cell lymphoma.     

Primary Cutaneous CD8+ CD30+ Anaplastic Large Cell Lymphoma: An Unusual Case with a High Ki-67 index—A Short Review

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a part of the spectrum of CD30⁺ cutaneous lymphoproliferative disorder, characterized by variable degrees of CD2, CD3, CD4 and CD5 expression by lymphoid cells. PCALCLs with an expression of cytotoxic phenotype (CD8⁺) and cytotoxic proteins are uncommon. Cutaneous CD8⁺ CD30⁺ lymphoproliferative lesions are difficult to classify, diagnose and may be the cause of misdiagnose. CD8⁺ PCALCL must be distinguished from CD8⁺ mycosis fungoides, lymphomatoid papulosis type D and primary cutaneous aggressive epidermotropic CD8⁺ T-cell lymphoma. Usually CD8⁺ PCALCL is an indolent disease with a favorable prognosis, except few cases can show poor outcomes. The high Ki-67 index points toward advanced PCALCL. Treatment modalities include surgical excision, radiotherapy and clinical monitoring. Chemotherapy is reserved for disseminated disease. We report a 59-year-old male presented with rapid development of multiple painful reddish-brown plaques and nodular ulcerative skin lesions over the left thigh region since 2 months. A diagnosis of CD8⁺ PCALCL with a high Ki-67 index was made on the basis of histology and immunohistochemistry, in co-relation with clinical presentation.     

In‐transit recurrence of Merkel cell carcinoma associated with Bowen's disease: The first reported case successfully treated by avelumab

A 65‐year‐old Japanese man presented with a dome‐shaped nodule, the base of which was contiguous with a dull brown plaque, on the left leg. After local excision of the cutaneous lesion and left inguinal lymph node dissection, several dermal and subcutaneous nodules developed successively on the left lower extremity. Hematoxylin–eosin staining of the primary cutaneous lesion demonstrated uniform neoplastic cells arranged in a trabecular pattern extending from the dermis to subcutis. Mitotic figures were abundant. Although the overlying epidermis was substantially intact, the Merkel cells had invaded the epidermis, resulting in Pautrier‐like microabscesses. The hyperplastic epidermis adjacent to the nodule consisted of abnormally growing atypical keratinocytes. The enlarged left inguinal lymph node and successive secondary nodules contained Merkel cells similar to those in the primary nodule. Immunohistochemically, most tumor cells were positive for CAM5.2, synaptophysin, chromogranin A, CD56 and vimentin. The tumor cells in the left inguinal lymph node were positive for CAM5.2, synaptophysin and cytokeratin 20 but negative for CM2B4, and less than 1% of the cells expressed programmed cell death ligand 1. The patient was treated with avelumab, which showed significant efficacy against the in‐transit recurrence. Two months later, all nodules had disappeared completely. We describe a case of in‐transit recurrence of Merkel cell carcinoma that was associated histologically with Bowen's disease and was successfully treated with avelumab. Although accumulation of additional cases is needed, avelumab therapy may be a useful treatment for in‐transit recurrence of Merkel cell carcinoma.     

Cutaneous sporotrichoid leishmaniasis resistant to pentavalent antimonial therapy: complete resolution with itraconazole

Sporotrichoid leishmaniasis is a sporadic form of cutaneous leishmaniasis, a protozoal infection, reported particularly in the Middle East. Clinically it occurs as nontender, subcutaneous, slightly erythematous nodules, often associated with lymphangitis, usually on exposed areas of the skin. Sometimes it occurs after treatment with a single dose of antimonials, and in older lesions, the biopsy can be negative for amastigotes. We report a case of cutaneous sporotrichoid leishmaniasis unresponsive to intralesional pentavalent antimonial therapy, which completely resolved after treatment with oral itraconazole. To our knowledge, this is only the third such case reported. We discuss the causes of dissemination of the nodular lesions and the negative results for amastigotes on re‐biopsed lesions.     

A case of cutaneous metastases of gastric carcinoma showing peculiar clinical features.

A 52-year-old male patient presented with multiple cutaneous nodules on the face, trunk, and upper extremities. Examination of a skin biopsy specimen disclosed numerous signet ring cells throughout the dermis. Histopathologic examination of the stomach, along with gastroscopy, revealed that the cutaneous metastases were of gastric origin. The metastatic skin lesion on the shoulder and the back of the patient grew relatively rapidly, showing an erysipelas-like lesion followed by prominently large tumor masses. The clinical appearance seen in our case is thought to be rare. Radiotherapy and chemotherapy appeared to be effective in reducing some tumors and the swelling on the anterior of the neck, and in prolonging life.     

Case of chromoblastomycosis with pulmonary involvement

Chromoblastomycosis is a slowly growing chronic cutaneous mycosis associated with a variety of cutaneous lesions. Extra‐dermal involvement is rare. A 58‐year‐old man was admitted to the hospital with nausea, vomiting, weakness and a history of weight loss. On inspection, he had a large verrucous mass in the sacral region, and two large subcutaneous nodules in the anterior thoracic wall. He claimed the lesions were several years old. Biopsy and histological studies were positive for chromoblastomycosis. Routine chest radiography showed hilar enlargement, and a chest computed tomography was ordered. Pulmonary nodules were evident, and endoscopically acquired samples were also positive for chromoblastomycosis. Extra‐dermal and systemic involvement in chromoblastomycosis is exceedingly rare and often associated with immunosuppression. There is only one other case of pulmonary chromoblastomycosis reported in the published work.     

Coexistence of Langerhans cell histiocytosis,Rosai–Dorfman disease and splenic lymphoma with fatal outcome after rapid development of histiocytic sarcoma of the liver

The coexistence of skin‐limited Langerhans cell histiocytosis (LCH) and Rosai–Dorfman disease (RDD) is an exceptional finding. The association of lymphomas and histiocytosis is also infrequent. We report the case of a 68‐year‐old man which presented an exceptional association of cutaneous LCH and RDD and splenic marginal zone lymphoma. He was stable for few years. Suddenly, the patient was admitted into Hematology Department with a remarkable enlargement of spleen and liver without enlargement of lymphadenopathies or skin lesions flare. He died 24 h later despite treatment with systemic chemotherapy combined with prednisone. Pre‐mortem biopsy showed infiltration with histiocytic sarcoma. We think that a transdifferentiation phenomenon could explain our case, although we could not show a clonal relationship between the cutaneous and the liver diseases. We also want to pay attention to the fact that a fast transformation to a more aggressive disease can occur long time after the presentation of the first lesion, a problem that stresses the importance of performing a close and permanent follow‐up of these patients.     

The morphologic spectrum of primary cutaneous anaplastic large T-cell lymphoma: a histopathologic study on 66 biopsy specimens from 47 patients with report of rare variants

Background:  Primary cutaneous anaplastic large T-cell lymphoma (PCALCL) is a well-defined entity with prognostic differences from the nodal counterpart [nodal anaplastic large cell lymphoma (NALCL)]. Several histological variants of NALCL have been characterized (common, lymphohistiocytic and small cell). However, studies on morphological variants of PCALCLs are lacking.
Methods:  We analyzed retrospectively the clinicopathologic features of 66 biopsies from 47 patients (M : F = 27 : 20; median age: 53 years; mean age: 51.8 years; range: 14–82) with PCALCL, in order to better characterize the spectrum of this unusual neoplasm.
Results:  The 'common variant' was the most frequent (40.4%). In contrast to NALCL, in PCALCL, marked reactive infiltrates are more commonly present. In fact, 26 cases were classified as 'inflammatory type' (15 cases) and 'lymphohistiocytic' (11 cases). Concerning the predominant cell morphology, large anaplastic cells (33%) were almost as frequent as large pleomorphic (36%) and small to medium-sized cells (26%). We reported for the first time in the skin 2 rare cases with the predominance of large cells with a 'signet-ring'-like appearance. Epidermotropism and presence of eosinophils were found in a proportion of cases in all PCALCL variants.
Conclusions:  PCALCL is characterized by variable histopathological presentations and a broad cytomorphologic spectrum.